THE VAGUE PATIENT

THE PATIENT WITH TOO MANY SYMPTOMS AND TOO LITTLE SIGNS

By Hatem Eleishi, MD    

By "Too many symptoms" we mean to refer to groups of patients who present with diffuse poorly localized aches or stiffness (remember also that pain is sometimes described by patients as stiffness). "Poorly localized pain" refers to a poorly localized pattern rather than site of pain description. That is, pain whose pattern and characteristics do not straightforwardly match with those resulting from abnormalities originating in any of the anatomical structures in the region or area from which the pain originates, whether these are musculoskeletal, neurological or vascular structures.
Thus, included in this group of patients will be patients complaining of diffuse or widespread musculoskeletal pains as defined by the ACR criteria for the diagnosis of fibromyalgia syndrome: pain that is present for at least 3 months in at least 2 contralateral quadrants in the axial skeleton.
The origin of pain in patients with "too many symptoms" may be the muscles (diffuse myalgias, diffuse stiffness), the bones (diffuse bony pains) or the joints (diffuse arthralgias 'polyarthralgias', diffuse stiffness).

By "too little signs", we mean to refer to the finding, on clinical examination of such patients, of:
1. Limited physical findings (a quantitative paucity of signs)
2. Physical findings that are not necessarily limited but do not complement with the symptoms to formulate the diagnosis of a definitive primary rheumatologic syndrome (a qualitative paucity of signs).

A "definitive rheumatologic syndrome" is one in which the patient's description of his/her symptoms (pattern of symptoms) targets specific receptors in the rheumatologist's mind and complements with consistent objective physical findings on examination so that both together help the physician make a definite primary rheumatologic diagnosis (as arthritis, bursitis, tenosynovitis, enthesitis...etc) which is essentially an anatomical diagnosis.
Thus, patients with 'too many symptoms and too little signs' present with vague symptoms and, on examination, will still show vague signs and are a constant source of frustration to practicing rheumatologists.

Evaluation of the patient with non-specific achiness requires consideration of a wide range of rheumatic, malignant, metabolic and psychiatric diseases. Complete physical examination (including pelvic, rectal and breast examination), basic laboratory testing as CBC, ESR, electrolytes, serum Ca, liver, kidney and thyroid functions and routine health maintenance screening (CXR, mammography, Pap smears, stool guaiac, prostate exams and PSA) often give clues to the diagnosis.

The main causes for such patterns of clinical presentations can be categorized into four main groups.

These are:
 

1. Endocrine and metabolic disorders

2. Fibromyalgia and related disorders

3. Psychiatric disorders

4. Other miscellaneous disorders

 

ENDOCRINE AND METABOLIC CAUSES
 

1.OSTEOMALACIA
2.PAGET’S DISEASE
3.HYPERPARATHYROIDISM
4.HYPOTHYROIDISM
5.MENOPAUSE
6.HYPERLIPOPROTEINEMIA
7.ELECTROLYTE DISTURBANCES
8.PRIMARY METABOLIC MYOPATHIES
9.HYPOPARATHYROIDISM
10.HYPERTHYROIDISM
11.ACROMEGALY

 

1. OSTEOMALACIA

OSTEOMALACIA is a pathologic loss of mineralized bone caused by reduction of calcium or phosphorus levels to below that required for normal mineralization of bone matrix.
The most common causes of osteomalacia beginning after early childhood are:
1. Concerning Calcium metabolism:
Reduced vitamin D absorption (biliary, proximal small-bowel mucosal or ileal disease), increased vitamin D catabolism (drug-induced increases in liver oxidase enzymes)
2. Concerning phosphate metabolism:
Acquired renal tubular defects with renal phosphate wasting: this entity includes (a) acquired renal tubular phosphate leaks [adult onset-vitamin D-resistant rickets], (b) Fanconi’s syndrome and renal tubular acidosis that is seen with Sjogren’s, lupus, monoclonal gammopathies and heavy metal poisoning.
Occasionally, patients with peptic ulcer on chronic magnesium-aluminium gel antacids develop phosphate depletion as large amounts of such substances convert dietary phosphate to insoluble complexes in the intestine.
Clinically: Patients with osteomalacia may present with fatigue, generalized bony pains, particularly in weight bearing bones. The pain may be severe enough to disturb sleep. Bony tenderness may be present (ribs, pubic rami, tibiae, periarticular). Deformities may be present as kyphoscoliosis, pelvic abnormalities and bowing of the legs. There may be difficulty walking (waddling gait) or getting out of a chair due to a combination of the pain and associated proximal myopathy. Sen¬sory polyneuropathy may occur. If the patient is hypocalcemic, paresthesias, tetany and seizures may be present. When osteomalacia is treated, the symptoms remit rapidly.
Investigations:
Patients should have X-rays performed. The radiological hallmark of osteomalacia is the Looser’s zones. These are translucent ribbon-like bands perpendicular to the surface of the bone, best seen in long bones, the pubic rami, the ribs and the scapulae. A bone scan may show multiple fractures not seen on the plain films. Bone biopsy is not usually necessary.
Investigations targeting the cause of osteomalacia:
a) In vitamin D deficiency osteomalacia, there is low-normal to decreased serum calcium, low serum phosphate, elevated bone ALP, a mild PTH elevation and decreased 25 OH D. A mild hyperchloremic acidosis is compatible with severe vitamin D deficiency and secondary hyperparathyroidism leading to proximal tubular bicarbonate wasting.
(b) In renal tubular phosphate leak syndromes, levels of serum calcium and 25 OH D are normal but serum phosphate levels are low. Marked hyperchloremic hypokalemic acidosis suggests renal tubular acidosis, a diagnosis that can be confirmed by inadequate urine acidification after an ammonium chloride load. Urinary calcium excretion is elevated in renal tubular acidosis, normal in renal phosphate leak and decreased in vitamin D deficiency.

To sum up, investigations of a patient with osteomalacia include: serum calcium, phosphorus, alkaline phosphatase, 25 OH D, PTH, urinary calcium and phosphorus and blood gases.
 

Case 1:
A 63-year old lady is seen by her GP complaining of generalized bony pains and muscle stiffness. Her pains are of a dull ache in quality and worse in her legs. She also complains of difficulty walking, getting up out of chairs and climbing stairs. She is otherwise well. She suffers from long-standing epilepsy for which she takes phenytoin. She is married and lives with her husband and grown-up daughter. She neither smokes nor drinks alcohol.
Examination: She looks well. Cardiovascular, respiratory and gastrointestinal systems: normal; Power is reduced symmetrically in her proximal upper and lower limb muscles. Tone, reflexes, coordination and sensation are normal. She has a waddling gait.
Labs: Hb 12.1; WBC 8.2; plat 370; ESR 7; Na, K, crea, glucose, albumin: normal; Ca 1.74 mmol/l (2.12-2.65); P 0.6 mmol/l (0.8-1.45); bilirubin 16 (3-17); ALT 25 (5-35), ALP 480 (30-300); urine: normal
Diagnosis:
Osteomalacia
 

Notes:
The symptoms and signs are those of a proximal myopathy. In addition, there is bone pain. The investigations show a low calcium and phosphate and raised alkaline. These symptoms and biochemical features suggest osteomalacia. In this patient, osteomalacia is likely due to vitamin D deficiency, most likely due to phenytoin that inhibits 25-hydroxylation of calciferol.
Her diet should be explored and she should be treated with oral calcium supplements and oral vitamin D.

 

Case 2:
A 59-year old lady presented with a 5 months duration of pain in the rib cage, shoulders and anterior thighs that sometimes prevented her from sleep. She also complained of lack of energy as well as difficulty getting out of a chair. She remarked that she had suffered several attacks of bleeding from her nose lately. She had been following up with a hepatologist for several years from some chronic liver condition. She had NIDDM for which she had been receiving oral hypoglycemics for diabetic for 4 years.
Examination: The patients looks well. BP: 150/80. Tenderness of the ribs and thighs. Decreased power in proximal muscles. Otherwise, examination is unrevealing.
Labs: Hb 13.2; WBC 2.700; plat: 74; ESR 7; ALP 809 (up to 122); total bilirubin 1.51 (less than 1.0); serum calcium 7.6 (8.4-10.2); serum phosphate 2.5 (3.5-5.0). Abdominal sonography: cirrhotic liver with splenomegaly, dilated portal vein, non-dilated common bile duct.
Diagnosis:
Osteomalacia secondary to vitamin D deficiency due to cholestatic liver disease.
Notes:
This patient has diffuse bony aches, proximal myopathy, low serum calcium and phosphorus and a high ALP. These data together suggest the diagnosis of osteomalacia. The patient also has evidence of cholestatic liver disease (history of chronic liver disease with elevated ALP and bilirubin). It must be noted here that the ALP elevation may be due to the bone disease or due to the cholestasic liver disease. These two can be differentiated by ordering ALP isoenzymes although evidence here suggests that both isoenzymes are likely to contribute to this elevation. The cholestatic liver disease leads to decreased absorption of fat soluble vitamins. This lady has evidence of deficiency of vitamin D (osteomalacia) and vitamin K (bleeding tendency). The low platelet count which is secondary to the splenomegaly associated with liver cirrhosis is still not low enough to contribute to the bleeding tendency in this lady.
This patient was prescribed vitamin D and calcium and experienced marked improvement of her symptoms within 2 months.

 

2. PAGET’S DISEASE

PAGET’S DISEASE is a chronic, patchy and scattered disease affecting localized areas of one or more bones. Affected areas are characterized by osteolysis that is followed by increased new bone formation. This bone structure and remodeling is, however, abnormal. If severe, lesions lead to bone deformity and enlargement. Clinically: Bone pain that may be associated with deformity. Increased blood flow to the affected bones leads to increased warmth over these areas so that if more than one third of the skeleton is involved, high output heart failure may result. Serum alkaline phosphatase is elevated and serum calcium and phosphorus are normal.

 

Case 3:
A 75-year old man presents with pain in his right thigh and left upper arm. The pain has been present for several months but has become worse. He is otherwise in good health and has had no serious previous medical illnesses. He has become progressively more deaf over the past year but has not sought help for this. The patient is a retired farmer and lives alone. He neither smokes nor drinks alcohol and is taking no regular medication.
Examination: His right leg is bowed laterally; his left humerus appears enlarged and warm; auditory acuity is markedly reduced in the right ear with reduction in air and bone conduction; examination is otherwise normal
Labs: Hb 13.1; WBC 8.2; plat 340; Na, K, crea, Ca, P, bilirubin, ALT: normal; ALP 584 (30-300)
Diagnosis:
Paget’s disease
 

Notes:
The combination of bony abnormality in the leg and arm and nerve deafness with a high alkaline phosphatase suggest that this patient has Paget’s disease. The disease mainly occurs in the elderly and is characterized by excessive and disorganized resoprtion and formation of bone. Pain occurs due to distension of the periosteum or from deformity causing arthritis. Affected bones are enlarged, deformed and warm. It can affect any bone, but commonly affects the pelvis and spine. The skull is often enlarged and compression of the 8th cranial nerve can cause deafness. Rarer complications are high-output cardiac failure secondary to high blood flow through the abnormal bone and osteosarcoma in the affected bone. The major biochemical change is an elevated ALP released by osteoblasts in overactive bone. Serum calcium is usually normal unless the patient is immobilized. The x-ray appearances are of enlarged bone, a resorbing front, thickened and deformed bone and multiple microfractures.
Bone scanning allows the extent of disease to be assessed and also the effects of treatment to be monitored. Rapidly enlarging pagetic bone deformity or severe pain would suggest osteosarcoma.
The patient should be given adequate analgesia. Patients only need specific treatment with bisphosphonates or calcitonin if they have severe bone pain, nerve compression or are awaiting orthopedic surgery. Surgery may be needed for fractures or if there is severe bone pain.

Causes of bony pain and deformity:
Osteomalacia (low serum calcium, phosphate, raised alkaline phosphatase)
Paget’s disease (normal calcium and phosphate, raised alkaline phosphatase)
Prostatic carcinoma and metastases (raised prostatic specific antigen PSA)
Osteoprorosis with fractures (Alkaline phosphatase may be raised)
Fibrous dysplasia

 

3. HYPERPARATHYROIDISM

Fatigue, muscular aches, generalized weakness and other neuromuscular complaints occur in the majority of patients with primary or secondary hyperparathyroidism. Weakness usually starts in the proximal muscles, often only in the lower extremities. Muscle enzymes remain normal in these patients. Additional findings include ligament laxity, tendon avulsions/ruptures, weight loss, epigastric pain (peptic ulcer), back pain (pancreatitis) and renal colic (renal calculi) and hypertension.
Diagnosis of primary hyperparathyroidism: presence of consistently elevated serum levels of calcium and PTH, and a low serum level of phosphate. The bone fraction of serum alkaline phosphatase is usually elevated in patients with bone disease. Hyperuricemia is frequent. Whereas urinary calcium excretion may be normal or low because of the renal calcium-retaining effects of PTH, patients with significant bone disease usually have an elevated urinary calcium excretion because of the increased filtered load.
Diagnosis of secondary hyperparathyroidism: a search should be done for the conditions that are associated with secondary hyperparathyroidism as vitamin D-deficiency states and chronic renal disease.

 

Case 4:
A 56-year-old office manager presents to her GP complaining of increasing tiredness over the past few months. She feels depressed and her husband has noticed her altered mood. She is sleeping poorly and tends to wake up early but denies any suicidal ideas. She also complains of mild nausea and constipation and notices that she has been more thirsty and passing urine more often. Her legs also ache. She has had two episodes of renal colic in the past three years. She has no significant past medical history. She is married and has three grown up children. She is a non-smoker. She is no medication.
Examination: the patient appears to have a rather flat emotional appearance with a poverty of facial expression; pulse 76/min; BP 170/95; jugular venous pressure: normal; heart sounds: normal; no peripheral edema; respiratory, abdominal and neurological systems: normal.
Labs: Hb 14.2; WBC 7.1; Plat 332; Na, K, crea, glucose, albumin: normal; Ca 3.25 (2.12-2.65); P 0.8 (0.8-1.45); bilirubin, ALT: normal; ALP 323 (30-300); urine: no protein, no blood
Comment:
The patient has typical symptoms of hypercalcemia, namely fatigue, nausea, vomiting, constipation, renal colic, bony pain and mood disturbance (most easily remembered as moans, stones, bones and groans). Other features sometimes seen are proximal myopathy, dyspepsia due to peptic ulceration and back pain due to pancreatitis.
 

Major causes of hypercalcemia:
1.Primary hyperparathyroidism (usually a single benign adenoma)
2.Carcinoma with skeletal metastasis
3.Carcinoma without skeletal metastasis (ectopic PTH secretion)
4.Multiple myeloma
5.Vitamin D intoxication
6.Sarcoidosis
7.Thyrotoxicosis
8.Prolonged immobility
9.Milk-alkali syndrome
In this patient, the low plasma phosphate level suggests that the cause is excessive parathyroid hormone secretion leading to reduced phosphate reabsorption by the renal tubules. Thus, the cause of hypercalcemia in this patient is either primary hyperparathyroidism or carcinoma with ectopic PTH secretion. In primary hyperparathyroidism, the alkaline phosphatase is normal or only slightly raised, whereas in malignancy it is often very high. A further clue that primary hyperparathyroidism rather than malignancy is the cause in this patient is the history of renal calculi suggesting that hypercalcemia is chronic. The PTH level was raised in this patient confirming the diagnosis of primary hyperparathyroidism. In this patient, a parathyroid scan diagnosed a parathyroid adenoma.
Hypercalcemia and PTH: In primary hyperparathyroidism, the PTH levels are inappropriately high for the prevailing calcium level (which may mean a high calcium and normal PTH). In all other cases of hypercalcemia, the PTH level is suppressed.
The definitive treatment for this patient is surgical removal of the parathyroid ademona. Her hypercalemcia has not caused volume depletion or renal failure and therefore treatment is not an emergency. However, in the presence of hypovolemia, the patient should be aggressively hydrated with normal saline and a diuresis maintained with furosemide. Bisphosphonates and calcitonin can be used to lower the plasma calcium temporarily.

Some of the important tests employed in investigating a patient with hypercalcemia:
Serum Ca and P: In patients with bony metastasis, both calcium and phosphate are elevated whereas in patients with excess PTH secretion, Ca is elevated and P is decreased.
Bone x-rays should be performed to exclude metastases, multiple myeloma and provide evidence of parathyroid bone disease (radiographic evidence is unusual in primary but common in secondary hyperparathyroidism of renal chronic renal failure).
Chest x-ray helps to exclude bronchial malignancy and sarcoidosis.
An electrophoretic strip should be ordered to exclude myeloma.
Parathyroid imaging: The parathyroid glands may be imaged either by ultrasound or by nuclear medicine scanning.

 

Case 5:
A 36-year old woman who had been undergoing long-term hemodialysis because of renal failure, presented with secondary hyperparathyroidism and progressive bony pains. After an uneventful subtotal parathyroidectomy (removal of 3-1/2 glands), her symptoms resolved in conjunction with normalization of parathyroid hormone levels. Subsequently, however, recurrent hyperparathyroidism and severe bone pain recurred.
Diagnosis: Parathyromatosis
Notes:
Parathyromatosis is a rare cause of recurrent hyperparathyroidism after parathyroidectomy. It consists of hyperfunctioning parathyroid tissues scattered throughout the neck, due either to intraoperative tissue spillage and subsequent implantation or to hyperplasia of parathyroid rests from embryologic development.
In this patient, the recurrence of hyperparathyroidism necessitated second and third neck explorations, during which parathyromatosis was discovered. A total thyroidectomy was performed because of the bilateral nature of the disease. Postoperatively, the patient's bone pain resolved substantially, although her parathyroid hormone levels remained high (Lee PC; Mateo RB; Clarke MR; Brown ML; Carty SE. Parathyromatosis: a cause for recurrent hyperparathyroidism. Endocr Pract 7(3):189-92, May-Jun 2001)

 

4. PRIMARY HYPOTHYROIDISM

The main muscle manifestations of this disorder are:
a. Stiffness, aching or painful muscles and cramps: seen in 50% of cases (Ramsey ID: Thyroid disease and muscle dysfunction. London. Whitefrairs Press. 1974). The myalgias and stiffness may be present during rest and are exacerbated on exposure to cold. Such muscular symptoms may be the presenting complaints in many patients without overt hypothyroidism.
b. Sluggish or slow movement, delayed muscle contraction and relaxation and delayed reflexes: classically found in most cases.
c. Myopathy: typically, patients with longstanding hypothyroidism have slowly progressive proximal muscle weakness often associated with compression neuropathies that rapidly recover with treatment and restoration of the euthyroid state. Occasionally, hypothyroidism may present with rhabdomyolysis and respiratory muscle weakness. The serum CK levels are typically elevated even if there are no other clinical symptoms of muscle involvement. Muscle enzymes return to normal levels after one to two months of thyroid replacement therapy.
d. In some an increase in muscle bulk: muscle hypertrophy with weakness and slow movements constitute the syndrome of Debre-Semelaigne which occurs predominantly in cretinous children; when accompanied by painful spasms it is given the name of Hoffmann’s syndrome and is then seen in myxoedematous adults. However, the two conditions tend to merge into each other and may even occur, although at different times, in the same patient. Slow relaxation and myoidema are prominent features of Hoffmann’s syndrome
e. Myoidema (i.e. ridging of muscle on percussion): myoidema is less common
The various muscle symptoms of hypothyroidism probably constitute a continuous spectrum, beginning with aches and pains and progressing to muscle cramping, proximal weakness and even hypertrophy in association with severe, long-standing hypothyroidism.
Other manifestations:
a. Ligament laxity, flexor tenosynovitis and carpal tunnel syndrome may be present. Approximately 10% of all patients with carpal tunnel syndrome have myxoedema. Fatigue is prominent feature of hypothyroidism.
b. Cold intolerance, puffy face and hands, goitre, hoarseness and deafness, bradycardia, weight gain, constipation, water retention, menorrhagia and infertility, mental slowing, inability to concentrate, poor memory, ataxia, depression, psychosis (myxedema madness), alopecia, dry skin, anemia (Fe or folate deficiency), hyperlipidemia.
NB: Clinical features common to both hyper- and hypothyroidism include fatigue, myopathy, angina and heart failure, infertility and psychosis.
Diagnosis: Primary hypothyroidism: Reduction in the total and free thyroxine levels accompanied by an increase in serum TSH levels. Patients with TSH levels above 5.0 mU/l are likely to have primary hypothyroidism. Total T4 discriminates well between hyperthyroidism, hypothyroidism and the euthyroid state. However, total T3 measurements, in contrast, are of little value in the investigation of patients suspected of being hypothyroid because in this condition the levels of T3 are often within the normal range.
 

HASHIMOTO’S THYROIDITIS: Patients complain of stiffness of the joints and muscles that is exacerbated on exposure to cold and that is worse on arising in the morning or after any period of immobility. Although this syndrome resembles that seen in hypothyroidism, yet, it can be present in autoimmune thryoiditis even in the absence of thyroid deficiency. Unusual chest wall pains and shoulder girdle pains of intermittent nature are described in 10% of patients. They last for several minutes to hours and are relieved by changes of position or mild exercises.

 

5. MENOPAUSE

MENOPAUSE is defined as the cessation of menstrual periods in women that occurs at about age 50 years. It is a well-defined event, although ovarian function begins to decrease one to two years earlier. A clinical diagnosis of menopause is made by the presence of amenorrhea for six to twelve months, together with the occurrence of symptoms of menopause such as hot flashes. If the diagnosis is in doubt, the pathognomonic finding is a high serum concentration of follicle-stimulating hormone (FSH). The absolute serum FSH concentration that is diagnostic of menopause varies depending upon the assay used; however, it will always be above the upper limit of normal for reproductive-age women, excluding the serum FSH values reached during the midcycle gonadotropin surge.
PERIMENOPAUSAL TRANSITION: Perimenopause is defined as the two to eight years preceding menopause and the one year after the last menstrual period. It is characterized by a normal ovulatory cycle interspersed with anovulatory (estrogen-only) cycles of varying length. As a result, menses become irregular, and heavy breakthrough bleeding, termed dysfunctional uterine bleeding, can occur during longer periods of anovulation. Thus, vaginal bleeding becomes unpredictable in both timing and amount. In addition, some women complain of hot flashes and vaginal dryness more typical of the postmenopausal period. Serum FSH concentrations may rise to the postmenopausal range during some cycles. However, high concentrations should not be used to diagnose menopause in menstruating women.
Symptoms and signs of decline and cessation of ovarian function:
A number of symptoms may arise soon after loss of ovarian function at the menopause. The most common are vasomotor instability (hot flashes*), psychological symptoms (as mood swings, depression*, anxiety, irritability and difficulties with memory and concentration). Later, there may be musculoskeletal problems (arthralgias and morning stiffness) and genitourinary problems (vaginal dryness and dyspareunia, increased urinary frequency and urge incontinence). Palpitation is another symptom that may perhaps be related to hormone deficiency. Approximately 40% of menopausal women develop symptoms serious enough to seek medical assistance.
Hot flashes: The most common acute change during menopause is the hot flash, which occurs in 75 percent of women. They are self-limited, with 50 to 75 percent of women having cessation of hot flashes within five years. Hot flashes typically begin as the sudden sensation of heat centered on the face and upper chest that rapidly becomes generalized. The sensation of heat lasts from two to four minutes, is often associated with profuse perspiration and occasionally palpitations, and is often followed by chills and shivering. Hot flashes usually occur several times per day, although the range may be from only one or two each day to as many as one per hour during the day and night. A distressing feature of hot flashes is that they are invariably associated with arousal from sleep. A continuing sleep disturbance may lead to fatigue, irritability, depression, difficulty concentrating, and other emotional and psychological symptoms that have been attributed to the menopause.
Sleep disturbance and depression: Studies that have investigated the relationship between depression and menopause have been conflicting. Most suggest that psychological distress may be related to stressful events and not to hormonal changes. Examples of stressful events around the time of menopause include mid-life adjustment, aging, children leaving home, career disappointments, chronic illness, and physical limitations. Some studies have found increased rates of depression among menopausal women who had a history of depression. Disturbed sleep pattern due to hot flashes may also contribute to fatigue and depression.

 

6. HYPERLIPOPROTEINEMIA
 

Patients attending lipid clinics have more musculoskeletal complaints than controls (Wysenbeek AJ, Shani E, Beigel Y: Musculoskeletal manifestations in patients with hypercholesterolemia. J Rheumatol 16:643-645, 1989), although other studies have not confirmed this association.
In a study of more than 1000 randomly selected Scandinavian men aged 50 to 60, there was no increased frequency of musculoskeletal complaints among those with either type II or type IV hyperlipoproteinemia compared with those whose lipoprotein levels were normal (Welin L, Larsson B, Svardsudd K, Tibblin G: Serum lipids, lipoproteins and musculoskeletal disorders among 50- and 60-year-old men. Scand J Rheum 7:7-12, 1977). In another study from England, only three of 166 patients with hyperlipoproteinemia (two with type II, one with type IV) had transient nondeforming polyarthritis and 8 patients (all with type IV) had gout (Struthers GR, Scott DL, Bacon PA, Walton KW: Musculoskeletal disorders in patients with hyperlipidemia. Ann Rheum Dis 42:519-523, 1983). The authors of this study concluded that noncrystalline causes of musculoskeletal symptoms in patients with hyperlipoproteinemia were uncommon.
However, later studies indicated that musculoskeletal symptoms may be the initial manifestation of metabolic disease. Musculoskeletal complaints were found to be significantly more common in patients with various types of hyperlipidemia than in controls, and these symptoms antedated the diagnosis of hyperlipidemia in 62% of the cases (Klemp P, Halland AM, Majoos FL, Steyn K: Musculoskeletal manifestations in hyperlipidaemia: a controlled study. Ann Rheum Dis 52:44-48, 1993). Awareness of these clinical manifestations may lead to earlier diagnosis and treatment with a reduction of morbidity and mortality.

 

Case 6:
A 55-year old woman presented with periodic symmetrical pain of the hands and feet of inflammatory type. Examination did not show objective joint signs, but nodules were present over the knuckles.
What is the diagnosis?
Palpebral xanthelasma. Tendon xanthomata. Familial hypercholestrolemia and familial combined hyperlipidemia (types IIb and IV).
Notes:
Occasional bone cysts may be identified in type IV. Erosive changes do not occur.
Management: weight reduction, reduction of saturated fatty acid intake to less than 10 percent of energy intake, cholestyramine for hypercholestrolemia, inositol nicotinate for hypertriglyceridemia.
 

7. ELECTROLYTE DISTURBANCES

Myalgias are caused by hypercalcemia, hypophosphatemia (both of which are also associated with weakness), hypomagnesemia, hypokalemia, hypernatremia (all of which are also associated with weakness and cramps). NB: hypocalcemia and hyponatremia cause only weakness and cramps but not mylagias and hyperkalemia causes muscle weakness but no cramps or myalgias.
Note: Myopathy could be secondary to hypercalcemia in a patient with hyper-reflexia.

 

8. PRIMARY METABOLIC MYOPATHIES
 

What are metabolic myopathies: Metabolic myopathies are myopathies that have in common an underlying abnormality in muscle that interferes with that tissue’s ability to produce or maintain adequate levels of energy. Metabolic myopathies are either primary or secondary. Primary metabolic myopathies include disorders of glycogen, lipid and purine metabolism, channelopathies (as hypokalemic periodic paralysis) in addition to a wide range of other less known inherited disorders. Secondary metabolic myopathies include endocrine diseases, metabolic disorders, nutritional abnormalities and electrolyte disturbances.

Inherited disorders of carbohydrate, lipid and purine metabolism are associated with episodic muscle damage ranging from myalgias and mild muscle enzyme elevation to frank rhabdomyolysis. Carnitine palmitoyltransferase (CPT) and muscle phosphorylase deficiency are the most common primary metabolic myopathies. Another known though less common metabolic myopathy is myoadenylate deaminase deficiency.

Muscle phosphorylase deficiency, or McArdle's Disease, is inherited in an autosomal recessive pattern. Affected individuals typically have a history of exercise intolerance in childhood followed by recurrent cramps, fatigue, and myoglobinuria in adolescence or early adulthood. CK levels do not completely return to normal between episodes of rhabdomyolysis.
In contrast, individuals with carnitine palmitoyltransferase deficiency have normal CK levels during inter-attack periods. Thus, serum muscle enzyme levels should be measured when the individual is symptomatic.
Another known disorder is myoadenylate deaminase deficiency. This condition may cause exercise intolerance, myalgias, cramps which are sometimes very mild and poorly defined. It can also present with myoglobinuria. CK levels, EMG (may sometimes show nonspecific myopathic changes) and muscle biopsy are all normal. The forearm ischemic test shows a normal lactate but no increase in the ammonia level or inosine monophosphate. Diagnosis is by immunohistochemistry. There is no specific treatment for this condition.

McArdle’s syndrome (myophosphorylase deficiency): Myophosphorylase deficiency is a metabolic myopathy that is considered to be the prototypic myopathic glycogen storage disease. In myopathies associated with disorders of glycogen metabolism, most individuals are well at rest and perform mild exercise without difficulty, because free fatty acids are the major source of energy under those conditions. In most individuals, the enzymatic block causes problems under conditions when carbohydrate is relied on for generation of ATP. This inability to replenish depleted high-energy phosphate stores results in exercise intolerance, cramping, contracture and muscle necrosis. This is the most common and easily understood presentation. For reasons that are not understood, some patients present with gradual onset of proximal muscle weakness. Clinically: Intolerance to exercise and activities of high intensity and short duration or those that require less intense effort for longer intervals. The exercise intolerance is associated with pain, fatigue, stiffness or weakness. In addition, painful muscle cramps may also occur and are associated with muscle necrosis, myoglobinuria and potentially reversible renal failure. Symptoms resolve with rest. Most individuals function well, provided they adjust their activities to a level below the threshold for symptoms and allow a brief rest immediately after the first sensation of muscle pain. This is referred to as the “second wind” phenomenon and is attributed to the combination of increased blood flow stimulated by increased muscular activity and the ability of alternative energy substrates (amino acids and fatty acids) to be mobilized and used to generate energy. The disease becomes symptomatic at any age but typically between ages 10 and 30 years of age. For unknown reasons, severe cramps and myoglobinuria are rare before adolescence. Some individuals complain only of being tired and having poor stamina whereas others develop progressive muscle weakness that tends to be proximal and may be misdiagnosed as polymyositis. The development of fixed proximal muscle weakness later in life is attributed to recurrent exertional muscle injury. Diagnosis: (1) Magnetic resonance spectroscopy: confirms the muscle biochemistry predicted by the known enzymatic block. With exercise, the expected decrease in pH is not seen and the recovery of energy-rich metabolites to baseline levels is delayed. (2) Elevated levels of CK in over 90% of patients. These levels escalate dramatically during symptomatic episodes. (3) Electromyographic studies: normal unless myoglobinuria is present. However, nonspecific abnormalities including increased insertional activity, an increased number of polyphasic low amplitude potentials and evidence of muscular irritability with fibrillations and positive sharp waves have been reported. The cramps that develop after vigorous activity or ischemic exercise are electrically silent. (4) The forearm ischemic exercise test: a useful but nonspecific tool. It is based on the fact that in normal individuals, venous lactate levels increase three to sixfold shortly after ischemic exercise but in myophosphorylase deficient individuals, levels do not change. This is because the glycolytic pathway is blocked when myophosphorylase is absent and consequently lactate cannot be released into the circulation. (5) Analysis of muscle tissue. Treatment: Although no specific treatment is available for myophosphorylase deficiency, aerobic exercise training and high protein diets have had positive effects. Myophosphorylase is the major repository of vitamin B6 in the body, accounting for 80% of the total body pool. Some myophosphorylase deficient patients show signs of subclinical viamin B6 deficiency and have reported greater resistance to fatigue with oral vitamin B6 supplementation.

Carnitine palmitoyltransferase deficiency: The most common symptoms of muscle affection in adult patients with lipid storage diseases are myalgia and progressive muscle weakness with or without episodic rhabdomyolysis. Individual with a lipid storage myopathy are likely to have other tissues involved as well as interference with energy production occurs in most organs. Carnitine palmitoyltransferase deficiency is one of the lipid storage diseases that is especially characterized by attacks of myalgias, cramps, stiffness or tenderness with myoglobinuria after prolonged exercise or fasting at times when fatty acids are the main source of cellular energy. Attacks are also precipitated by cold exposure, infection, high fat intake, emotional stress and the use of ibuprofen or diazepam. Mild attacks may be experienced in childhood but severe attacks usually do not occur until the teenage years or later. Intermittent episodes of severe muscle cramping and passage of rose or darkish urine may be ignored or puzzling. This enzyme deficiency may be the most common cause of exercise-induced rhabdomyolysis, myoglobinuria and proximal muscle pain and weakness in young adult males. Middle-aged women may present with chronic history of diffuse aching and fatigue provoked by fasting, high fat intake or prolonged exertion. In contrast to patients with glycogen storage diseases that also cause myoglobinuria, patients with carnitine palmitoyltransferase deficiency can perform brief intervals of intense exercise and cannot abort attacks with rest. Diagnosis: Serum CK levels are normal except during episodes of symptomatic rhabdomyolysis or with prolonged fasting. Serum lactate levels increase in a normal fashion after forearm ischemic exercise. Proton magnetic resonance spectroscopy may be helpful in diagnosis. Electrophysiologic studies and muscle tissue are entirely normal between attacks. Lipid accumulation is rarely observed in muscle. The diagnosis is made by measuring carnitine palmitoyltransferase activity in muscle. Management: consists of avoidance of both prolonged strenuous exercise and fasting. This will prevent most attacks. Infection may not be preventable but the need for adequate rest during an infection must be emphasized. High-carbohydrate diet low in long-chain fatty acids supplemented with medium-chain fatty acids and L-carnitine has been beneficial. Myoglobinuria constitutes a medical emergency because it may lead to renal failure. The renal failure is reversible if recognized and treated appropriately.

Myoadenylate deaminase deficiency: this is one of the disorders of purine metabolism. Some individuals with this condition complain of exercise intolerance due to fatigue with postexertional cramps and myalgias, but most are asymptomatic. Secondary or acquired deficiencies have been reported in association with influenza-like illness, polymyositis, systemic lupus, systemic sclerosis, hyperthyroidism, diabetes and gout. Diagnosis: Levels of serum enzymes are usually normal. EMG is normal or nonspecific. The measurement of venous lactate and ammonia concentrations after forearm ischemic exercise is effective for screening for this condition. Patients experience increase in lactate but no change in levels of ammonia compared with baseline.

Case 7:
A 21-year old female presented with pain in the muscles on walking 200 meters of 5-years duration. With perseverance, the patient was able to walk the pain off. After particularly strenuous periods of exercise, the patient would pass dark-colored urine. She also complained of weakness of the muscles of the pelvic girdle. There were no objective signs on examination
EMG showed myopathic changes. The forearm ischemic lactate test was abnormal: no increase in lactate.
Diagnosis:
McArdle’s syndrome
A muscle biopsy revealed absence of myophosphorylase on muscle biopsy
 

9. HYPOPARATHYROIDISM

Hypocalcemia in hypoparathyroidism results in muscle weakness and fatigue.
In primary hypoparathyroidism, there is inadequate secretion and low serum levels of PTH. In pseudohypoparathyroidism, the serum levels of PTH are high but there is end-organ resistance to the action of PTH. There are two types of pseudohypoparathyroidism: type Ia and type Ib. In type Ia (Albright’s hereditary osteodystrophy), PTH resistance is associated with a constellation of abnormal features including short stature, brachydactyly variable mental retardation and ectopic ossification. The routine examination of the clenched fist may suggest Albright’s hereditary osteodystrophy: the foreshortened fourth metacarpal produces the so-called ‘knuckle, knuckle, dimple, knuckle’
In type Ib, the condition is limited to hormonal resistance.
NB: In another variant of Albright’s hereditary osteodystrophy, patients have the abnormal physical features of type Ia but have no hormone resistance (and thus have no hypocalcemia). This condition is termed pseudopseudohypoparathyroidism.

Case 8:
A 22-year old male presented with generalized muscle weakness and fatigue and generalized arthralgia on exposure to cold. There was a past history of excision of an osteoid metaplasia from the upper right thigh at the age of 10 years. Examination: The patient was short-statured, had mild mental retardation, small hands and feet, positive Chvostek sign and Trousseau sign, fine intension tremor affecting the hands.
Investigations: hypocalcemia, PTH 1330 pg/ml (50-330 pg/ml)
Diagnosis: Pseudohypoparathyroidism type Ia (Albright’s hereditary osteodystrophy)

 

10. HYPERTHYROIDISM

Thyrotoxic myopathy: can be mild, characterized by fatigability, weakness and minimal atrophy, or it can be extreme, characterized by severe weakness and proximal wasting. Muscle enzymes are, however, typically not elevated. Also myasthenia gravis and thyrotoxic periodic paralysis that is similar to the periodic paralysis of primary hypokalemia may occur.
Other findings: Fatigue, heat intolerance, tachycardia, weight loss despite increased appetite, diarrhea, polyuria, amenorrhea and infertility, irritability, restlessness, tremor, emotional lability, psychosis, pruritis.
Scalpulo-humeral periarthritis is the main articular complication of hyperthyroidism. True manifestations of "thyrotoxicosis rheumatism" are unusual and may be linked with a direct toxicity of the thyroid hormones on joint cartilage or with an autoimmune manifestation of hyperthyroidism. Molinier et al., in 1998, reported two cases of polyarthralgias associated with hyperthyroidism. In both cases, arthralgia totally regressed after thyroid treatment: Two 79-year-old and 59-year-old women developed manifestations of polymyalgia rheumatica and psoriatic arthritis respectively. Corticosteroid therapy was ineffective and followed by manifestations of hyperthyroidism. The first patient was treated with carbimazole and the second with thyroidectomy. Once the hyperthyroidism was controlled, both patients experienced a dramatically rapid cure of their arthralgias Molinier S; Paris JF; Marlier S; Galzin M; Amah Y; Carli P: Polyarthralgia disclosing hyperthyroidism. Two case reports. Presse Med 1998 Sep 12;27(26):1324-6).
Diagnosis of hyperthyroidism: Elevation of serum levels of total or free T3 and T4 with low TSH levels. Symptomatic hyperthyroidism has been shown to be accompanied almost without exception with by TSH levels below 0.01 mU/l. Total T3 measurements may be of more value than those of T4 in patients suspected of being hyperthyroid when they may rise before changes in total T4 levels are detectable.
Patients with TSH levels between 0.01 and 1.0 mU/l, in whom there is no clinical evidence of hyperthyroidism pose diagnostic difficulties.
 

ANTI-THYROID DRUGS: The administration of antithyroid drugs may be followed by syndromes resembling either RA or systemic lupus erythematosus, especially in children.

 

11. ACROMEGALY
 

About one third of patients with acromegaly may present because they notice a change in their facial appearance, another one third have associated disturbances such as visual field defects, carpal tunnel syndrome or headaches and the remainder are recognized to be acromegalic when seeking medical attention for another reason. Carbohydrate metabolism is often disturbed leading to hyperglycemia and glycosuria. This is because growth hormone antagonizes the insulin-mediated cell uptake of glucose. The diagnosis of acromegaly is confirmed by finding a raised growth hormone level that does not suppress normally in a glucose suppression test.
 

Musculoskeletal symptoms and signs:
Symptoms: Gradual proximal, later generalized, weakness and decreased exercise tolerance and fatigue are the usual complaints, followed by myalgias, cramps, and muscle twitching. Signs: The muscles may feel flabby, with weakness out of proportion to muscle mass. Investigations: The serum creatine kinase and aldolase levels, although usually normal, may be increased as a reflection of patchy necrosis.
Additional findings: Vague paresthesias involving several peripheral nerves (may be the earliest symptoms), palpable enlargement of the ulnar or popliteal nerves (with pares-thesias, decreased or absent deep tendon reflexes, distal wasting, and even footdrop) and typical carpal tunnel syndrome that is usually bilateral. Soft tissue hypertrophy and Raynaud’s phenomenon may also occur. Thickening of the blood vessel walls may contribute to its development

 

FIBROMYALGIA AND RELATED SYNDROMES
 

1. FIBROMYALGIA SYNDROME
2. MYOFASCIAL PAIN SYNDROME
3. CHRONIC PAIN SYNDROME
4. CHRONIC FATIGUE SYNDROME
5. RESTLESS LEG SYNDROME
6. PERIODIC LIMB MOVEMENT DISORDER
7. POLYMYALGIA RHEUMATICA
8. HYPERMOBILITY SYNDROME
9. STIFFMAN SYNDROME
10. TIETZE'S SYNDROME AND COSTOCHONDRITIS

 

1. FIBROMYALGIA SYNDROME (FMS)

Site: Most fibromyalgia patients have widespread pain and/or stiffness involving the spine and all the limbs together with the presence of characteristic tender points. The pain is predominantly articular in some patients and muscular in others. Timing: Pain or stiffness is particularly present in the morning or the evening, but 30% of patients describe no consistent pattern. Aggravating factors: cold or humid weather, mental anxiety or stress, and poor sleep, similar to pain in RA patients.
 

2. MYOFASCIAL PAIN SYNDROME (MPS)
 

Myofascial pain syndrome is a syndrome of prolonged local or regional (less commonly, generalized) muscle pain at rest and with movement, without discernable disease. The pain is associated with stiffness, aching, gelling, tightness, numbness, tingling, weakness or cooling in a localized area of the body, along with trigger points, taut bands and localized muscle twitch found in the involved muscles. As in the case with fibromyalgia, the condition, when chronic, can be associated with deconditioning, psychological dysfunction, symptoms of depression and disturbed stage 4 sleep or nonrestorative sleep pattern. It is, however, possible that patients with generalized myofascial pain fulfill the criteria for fibromyalgia and patients with tender points in fibromyalgia have trigger points in the same location (Bennet RM. Myofascial pain syndrome and fibromyalgia syndrome: A comparative analysis. Adv Pain Res Ther. 17:43-65, 1990).
The trigger point is the “lesion” of myofascial pain and is the result of injury. Trigger points appear in predictable locations, usually in the midportion or belly of the affected muscle. Flat palpation of a relaxed muscle under passive stretch best locates these small (less than 1cm2), discrete tender spots. Sustained pressure (10 seconds) or penetration by a needle usually causes referral of pain into the “zone of reference” typical of that muscle. There may or may not be a palpable nodule at the site. Often the trigger point is located within a taut band in a muscle with decreased range of motion.
The trigger point may represent sensitive areas over the site of innervation of the underlying muscle, where it is most accessible to percutaneous electrical stimulation. Trigger points presumably involve a circular or reflex pain-spasm-pain cycle, likely involving the autonomic nervous system. Although trigger points, when indurated, do not disappear with general anesthesia, they are abolished with a sympathetic nerve block. Using an electromyogram recording, a 7-fold increased muscle tension reading in trigger points was noted that was then reduced to 1.5 times normal after bupivacaine injection. Skin resistance is lower in the vicinity of a trigger point than in the surrounding tissue and this can be reversed with treatment.
Muscle fiber injury as a cause for the induration and abnormality of trigger points has been suggested. Muscle injury may heal more slowly due to depressed levels of somatomedin C. Inasmuch as growth hormone is secreted during sleep, and sleep is of poor quality in patients with myofascial pain and also in patients with fibromyalgia, who may also be found to have trigger points in addition to the tender points.
Trigger points, characteristic of myofascial pain disorder, can be eliminated with local modalities including ice massage, stretching, dry needling or local injections of an anesthetic agent alone, or combined with a corticosteroid agent. Tender points, however, cannot be eliminated by these methods but may be rendered less painful.
The taut band: Trigger points are characteristically found within taut bands of muscle. The taut band is a shortened group of muscle fibers and can be best palpated by sliding the skin and subcutaneous tissues perpendicularly across the fibers of the muscle. These bands are electrically silent and therefore not due to spasm. Once the taut band is found, palpation along it will lead to the most tender point “the trigger point”. “Snapping palpation” of the band gives rise to another cardinal sign of myofascial pain, the local twitch response.
The local twitch response: When one “snaps” the taut band containing a trigger point, a transient contraction of the band’s muscle fibers occurs. This sign is diagnostically important although its pathophysiological significance is unclear. Needling of a trigger point also produces a twitch response. The technique of snapping palpation requires significant skill and its validity as a diagnostic sign has not been established.
 

Chronic regional myofascial syndromes: the single-muscle myofascial pain syndromes are usually acute and follow an episode of muscle overload. In some cases, the pain persists and spreads to other, usually synergistic, muscles. Many perpetuating factors encourage transformation to a more widespread pain problem. Mechanical factors include postural stress, muscle imbalances and skeletal asymmetries. These can put additional stress on surrounding muscles, leading to spread of dysfunction and pain. Systemic perpetuating factors purportedly include anything jeopardizing the energy supply to muscle (i.e. anemia, endocrine imbalances as low thyroid function, vitamin deficiencies).

Treatment of muscle pain syndromes: (mainly applies to MPS and FMS):
A. Elimination of contributing factors:
Vitamin deficiencies: give plenty of B vitamin sources
Correction of poor posture and poor body mechanics, leg length discrepancy
Vocational and avocational muscle overuse: this more commonly appears with the more localized forms of muscle pain.
Frequent breaks for stretching and changes of position or task
Psychologic stress: the more chronic and widespread the muscle pain syndrome, the more likely that psychological stress plays a role: management includes psychiatric consultations and CBT approach (cognitive behavioural therapy) for the management of chronic pain
Poor sleep: manage with a tricyclic antidepressant (amitryptiline 10-25mg or trazodone 25-75 mg) 1 hour before sleep +/- a selective serotonin re-uptake inhibitor (SSRI) in the morning (fluxetine 20mg in the morning).

B. Treatment of motor dysfunction:
Physical therapy: to decrease pain, restore normal range of motion, restore normal neuromuscular functioning and improve fitness:
To reduce pain:
One method combines hot packs and high-voltage galvanic stimulation to the most symptomatic area. This can be followed by deep sedative massage or gentle soft tissue mobilization. The use of these modalities should be limited to the early treatment phase to avoid patient dependence and the persistent notion that something must be done to them in order to get “fixed”.
To restore range of motion:
A general stretching program with special emphasis on muscle groups found to be “tight” on examination is a basic part of treatment. The patient should learn to do this several times a day. Using heat before gentle prolonged stretching may improve its effectiveness and lessen its discomfort.
To restore normal neuromuscular functioning:
This goal lies in restoring normal resting tone and fluid movement without co-contraction of agonists and antagonists. Surface EMG biofeedback over specific areas can be helpful especially with the postural muscles which often function subconsciously. Multiple sites can be scanned and areas of increased activity are targeted for specific relaxation exercises to help patients eliminate co-contraction and teach them to return their muscles to electrical silence after contraction, a state that is often missing in patients with muscle pain. Also, a short intense course of biofeedback training might be needed (Kasman G, Cram J, Wolf S: Clinical application is surface electromyography: Chronic musculoskeletal pain.Gaithersburg, MD, Aspen, 1998).
Fitness program:
Once pain has been reduced and motor dysfunction minimized, a very graduated aerobic fitness program can be instituted. The extent and chronicity of the muscle pain problem parallel the need for this treatment step. It is important to stress a very gradual return to activity to avoid fatigue and increased muscle pain.

C. Local treatments:
Spray and stretch:
The mainstay of myofascial pain syndrome treatment. The vapocoolant spray is used to reflexively relax the muscle to allow an adequate stretch. One maintains a sweeping pattern of spary in the direction of the muscle fibers as the muscle is passively stretched by the patient or the clinician’s free hand. The coolant spray serves to distract the patient and possibly relax the treated muscle to allow for a more effective stretch. The prolonged stretch is the key element and is what provides pain relief.
Injection:
Some practitioners simply inject the general area of the most intense pain. Others take great care in locating the “trigger point” watching for the twitch response on entering it with the needle. Dry needling appears to work as well as any other type, but most physicians use a local anesthetic for the sake of patient comfort. The addition of corticosteroids to the injection has many advocates but likely adds little cost to the procedure. Proponents of injection focus on finding the primary trigger point, which, when treated successfully, leads to resolution of many of the secondary trigger points. Treating only the secondary points without finding the primary point is one reason for treatment failure.
The use of ischemic compression to treat trigger points:
The theory is that sustained pressure over the pathological area induces increased blood flow on release of pressure with hyeperemia of the skin. This in turn reverses the assumed localized ischemia in the underlying muscle. The digitally applied pressure lasts for about 1 minute at gradually increasing pressure as tolerated up to 30lb.

 

3. CHRONIC PAIN SYNDROME (CPS)

Chronic pain syndrome is an abnormal condition in which pain is no longer a symptom of ongoing tissue injury, but one in which pain and pain behavior become the primary disease processes. You can have chronic pain without having “chronic pain syndrome”. Chronic pain syndrome is distinct from chronically or intermittently painful disease in which the patient experiences pain, but manifests function and behavior appropriate to the degree of tissue injury. In chronic pain syndrome, subjective and behavioral manifestations of pain persist beyond objective evidence of tissue injury. In chronic pain syndrome, the original causes are often blurred by subsequent complications of multiple procedures, compensation factors, medication dependency, inactivity and psychosocial behavior changes (Brena, 1978).
Etiology: An organic etiology for the pain is present at first. The patient’s perception of the pain is modified by psychological, social and environmental factors to yield the chronic pain syndrome. A popular model hypothesizing the development of chronic pain syndrome is the neurosensitization syndrome (NSS). This is defined as: a syndrome of subjective discomfort and objective functional disability; that often appears excessive in duration and severity with respect to the identified initiating injury or event; that may be resistant to conventional medical and psychological treatment modalities; and that is hypothesized to develop as the result of progressively enhanced sensitivity or reactivity of central nervous system (CNS) mechanisms at the neurophysiological, biochemical, and intracellular levels (Miller, 2000)
In short, patients suffer from a chronic painful condition and exhibit maladaptive patterns of behavior for dealing with their persistent pain.
The typical 5 Ds of the syndrome include drug abuse or misuse, dysfunction or decreased function in life, disuse resulting in loss of flexibility, strength and endurance, depression or depressed mood, disability resulting in inability to perform activities of daily living or pursue gainful employment. A sixth D can be added and that is disordered sleep pattern where stage 4 sleep is significantly adversely affected. The patient may also present with tender points as found in fibromyalgia or trigger points as found in myofascial pain syndrome.
Management: includes behavioral and psychological approaches, pharmacological treatment, physical therapy and biofeedback.
Tricyclic antidepressants are extensively used in the treatment of various chronic pain syndromes (King and Kelleher, 1991). Newer antidepressants, namely fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, trazodone, nefazodone, bupropion, mirtazapine, and venlafaxine, have also been considered for this indication. Making generalizations regarding the use of these drugs as analgesics is difficult, given the limitations of existing data (Ansari, 2000)
References:
Ansari A: The efficacy of newer antidepressants in the treatment of chronic pain: a review of current literature. Harv Rev Psychiatry 2000 Jan-Feb;7(5):257-77, Jan-Feb 2000)
Brena SF. Chronic pain: America’s hidden epidemic. New York, Atheneum/SMI, 1978.
King JC, Kelleher WJ. The chronic pain syndrome: The inpatient interdisciplinary rehabilitative behavior modification approach.Phys Med Rehabil State Art Rev. 5(1):165-175, 1991.
Miller L: Neurosensitization: A model for persistent disability in chronic pain, depression, and posttraumatic stress disorder following injury. NeuroRehabilitation 14(1):25-32, 2000.
Patil JJP. Prevention and principles of treatment of chronic pain syndrome in soft tissue injury. Nova Scottia med J. 142(Aug):141-143, 1993.

 

4. CHRONIC FATIGUE SYNDROME (CFS)

Disabling fatigue of at least 6 months duration usually accompanied by symptoms suggestive of viral infection as acute onset with flu-like symptoms, recurrent pharyngitis, adenopathy, and low-grade fever. It is also associated with chronic myalgias, arthralgias and parasthesias.
Initially a chronic Epstein-Barr virus (EBV) infection was implicated, but it soon became clear that there was no specific causative relationship between EBV and CFS. Many viruses may nonspecifically trigger it. Although this condition has been variously called postviral fatigue syndrome, epidemic neuromyasthenia, and chronic EBV syn¬drome, CFS is the term commonly used.
Chronic fatigue syndrome and fibromyalgia are similar, overlapping syndromes. A significant number of fibromyalgia patients have such common CFS symptoms as recurrent pharyngitis (54%), recurrent adenopathy (33%), low-grade fever (28%) and acute onset with flu-like symptoms (55%). Conversely, among patients with CFS, TPs and chronic myalgias were found to be significantly more common than in healthy controls. Other striking similarities between the two syndromes include a female preponderance with a similar age distribution, arthralgia, headache, paresthesia, irritable bowel syndrome, and depression. Thus, patients with CFS may represent a subgroup of fibromyalgia patients with severe fatigue, and present to physicians predominantly for this problem.
Gantz and Coldsmith provide a review of Multiple Internet Web sites information on chronic fatigue syndrome (CFS) and fibromyalgia. They classified the identified sites according to their content and target audience and judged them according to suggested standards of Internet publishing. Fifty-eight sites were classified into groups as follows: comprehensive and research Web sites for CFS and fibromyalgia, meetings, clinical trials, literature search services, bibliographies, journal, and CFS and fibromyalgia Web sites for the patient (Gantz NM; Coldsmith EE ngantz@pinnaclehealth.org: Chronic fatigue syndrome and fibromyalgia resources on the world wide web: a descriptive journey. Clin Infect Dis 15;32(6):938-48, Mar 2001).

 

5. RESTLESS LEG SYNDROME (RLS)
 

Restless legs syndrome (RLS) is characterized by an unpleasant sensation that is difficult-to-describe or that is described as “crawling of insects,” “full of writhing worms,” and “funny numbness” sometimes associated with pain. Site: usually in the calf of the legs, but sometimes in the feet and the thighs. Timing: Unlike paresthesia of peripheral neuritis, which is constantly present irrespective of activities, the discomfort of RLS is present during inactivity, typically in the evening while resting in a sitting position and before sleep. Therefore patients with RLS often have problems with initiating and maintaining sleep.
Ameliorating factors: The symptoms are usually improved or relieved by movements of the legs and the feet as well as by walking. The patients may feel an imperative desire to move lower legs because of paraesthesias or dysesthesias that are sometimes associated with pain and that occur at rest. Incidence: Men and women are equally affected, the common age being be-tween 50 and 60 years. Associations: A wide variety of conditions have been described to be associated with RLS; however, true association is probably limited to iron deficiency, pregnancy, and uremia. About one third of patients with RA and FMS have RLS. RLS has shown a consistent association with nocturnal myoclonus.
Pathophysiologic mechanisms of RLS are unknown, but a central mechanism, including decreased dopamine activity, has been suggested. No pathologic changes have been demonstrated in leg muscles. Laboratory tests are normal, with the exception of iron deficiency in some patients.
Treatment: The treatment of choice for RLS is levodopa (100 to 200 mg) taken at bedtime. In case of augmentation or time shifting transfer to dopamine agonists should be considered. Alternative medications are opioids, benzodiazepines, clonazepam (0.5 to 2mg), or some antiepileptic drugs (carbamazepine 100-300mg or gabapentin) (Eckardt KM; Trenkwalder C: Restless legs syndrome. Therapy according to plan. MMW Fortschr Med 28;143 Suppl 2:13-7, May 2001).
RLS is a benign condition, but the symptoms are severe enough to significantly interfere with social life, such as going to movies, in some patients.
 

6. PERIODIC LIMB MOVEMENT DISORDER (PLMD)

Periodic limb movement disorder (PLMD) is the new term recommended in the International Classification of Sleep Disorders, replacing the older term nocturnal myocIonus. PLMD is known to be significantly associated with restless leg syndrome; both conditions frequently occur in the same patient. An association has been suggested to exist between PLMS and upper airway resistance syndrome (UARS). A high percentage of PLM with arousals correlated with breathing events due to increased effort in UARS (Exar EN; Collop NA: The association of upper airway resistance with periodic limb movements. Sleep 15;24(2):188-92, Mar 2001). Nocturnal myoclonus may occur in fibromyalgia patients as well as in patients with Parkinson’s disease treated with levodopa and in obstructive and central sleep apnea, which should be ruled out appropriately. Periodic limb movements in sleep (PLMS) may occur in up to 6% of the general population (according to US statistics) and is more common in the elderly.
PLMD is characterized by repetitive, stereotyped brief movements of one or both lower extremities that occur primarily during non-REM sleep. The sudden movement involves dorsiflexion of the ankle and the toes, with or without flexion of the leg at the knee and of the thigh at the hip. The muscle contraction complex usually lasts between 0.5 and 4.0 seconds, recurring approximately every 20 to 40 seconds, over a period of several minutes to hours, with predictable and remarkable regularity. Clinically, patients describe themselves as restless sleepers and find their bed sheets in disarray in the morning. Often the sleep partners complain of being kicked, although patients themselves may not be aware of such activities. The mean age of onset is between 47 to 56 years, with no significant gender differences. Older patients have been reported to have more-severe symptoms. PLMD should be distinguished from “sleep starts” (hypnic jerks), which occur at the onset of sleep, usually involving all the extremities as well as the trunk simultaneously.
Patients with PLMD complain of excessive daytime sleepiness and insomnia, but a causal relationship has not been established.
Etiology: Provini et al. (2002) hypothesized that an abnormal hyperexcitability along the entire spinal cord, especially its lumbosacral and cervical segments might serve as the primary cause of PLMS, triggered by sleep-related factors located at a supraspinal but still unresolved level (Provini F; Vetrugno R; Meletti S; Plazzi G; Solieri L; Lugaresi E; Coccagna G; Montagna P: Motor pattern of periodic limb movements during sleep. Neurology 24;57(2):300-4, Jul 2001).
Diagnosis: Polysomnography to record periodic limb movements in sleep is necessary for the diagnosis. Only patients who meet specific diagnostic criteria should be treated pharmacologically (Bjorvatn B; Holsten F; Skeidsvoll H bjorn.bjorvatn@isf.uib.no: Periodic limb movements in sleep--can and should this condition be treated? (A short case history is also presented here). Tidsskr Nor Laegeforen 2001 Aug 10;121(18):2169-72, Aug 2001).

The different types of motor activity and movement disorder which occur during sleep include:
Normal activity
Paroxystic episodes: parasomnias; abnormal movements such as nocturnal paroxystic dystonia, which is very similar to epilepsy of frontal origin; nocturnal epileptic crises and especially periodic movements of the limbs and the restless legs syndrome, which is relates to it. Physiological cyclical fluctuations of sleep are common to all these conditions and due to cortico-subcortical changes in excitability (Garcia-Jimenez MA leoan@grupobbva.net: Movement disorders and motor activity during sleep. Rev Neurol 16-31;32(6):574-80, Mar 2001)

Treatment: Clonazepam at a bedtime dose of 0.5 to 2 mg is considered the first choice of treatment. Other drugs often used include baclofen (20 to 40 mg at bedtime), temazepam, and imipra¬mine. Tricyclic drugs in general are believed to aggravate PLMD.
Melatonin has been suggested to enhance the circadian rhythmicity of locomotor activity with a reduction of sleep motor activity (Kunz D; Bes F. kunz.d@psychiatry.mu-luebeck.de: Exogenous melatonin in periodic limb movement disorder: an open clinical trial and a hypothesis. Sleep 15;24(2):183-7, Mar 2001)
Note: Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are currently treated with substances of four classes: dopaminergic agents, which are considered the drugs of choice, benzodiazepines, opioids and anticonvulsants (Saletu M; Anderer P; Saletu-Zyhlarz G; Prause W; Semler B; Zoghlami A; Gruber G; Hauer C; Saletu B: Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol 11(2):153-61, April 2001)
 

7. POLYMYALGIA RHEUMATICA

 
Polymyalgia rheumatica is a systemic inflammatory syndrome of older individuals that is characterized by pain and stiffness in the shoulder and/or pelvic girdles. There is a strong relationship between the occurrence of polymyalgia rheumatica and temporal arteritis. It occurs mostly in individuals above 60 years. There are bilateral symptoms involving two of three areas (neck, shoulder girdle or hip girdle) for at least 1 month and the ESR is characteristically more than 40 but may be normal or only mildly elevated.
Clinical manifestations: Stiffness and pain are usually insidious in onset, symmetric, and profound. They involve more than one area (neck, shoulders girdles, pelvic girdles). However, at times, the onset is abrupt or the initial symptoms are unilateral and then progress to symmetric involvement. The shoulder is often the first area to be affected and a single area may be the predominant source of pain.
The magnitude of the pain limits mobility. Stiffness and gelling phenomena are dramatic. Pain at night is common and may awaken the patient. Patients may complain of a sensation of muscle weakness due to the pain and stiffness.
Physical findings are less striking than what would be expected from the history. Patients may appear chronically ill due to the presence of weight loss, fatigue, depression and low-grade fever. The neck and shoulder are often tender and active shoulder movement may be limited by pain. With longer duration of illness, capsular contracture of the shoulder (limiting passive motion) and muscle atrophy may occur. Joint movement increases the pain which is often felt in the proximal extremities, not the joints. Clinical synovitis is most frequently noted in the knees, wrists and sternoclavicular joints. Joint effusions have WBC counts that range between 1000 and 20,000 cells/mm. Carpal tunnel syndrome may be present. Muscle strength testing is often confounded by the presence of pain. However, strength is normal unless disuse atrophy has occurred.
Thus, the diagnosis of polymyalgia rheumatica is a clinical one relying on the features in the clinical setting.

Differential diagnosis:
Fibromyalgia: tender points, normal ESR.
Hypothyroidism: elevated TSH, normal ESR.
Depression: normal ESR.
Polymyositis: weakness predominates. Elevated CPK, abnormal EMG.
Malignancy: clinical evidence of a neoplasm.
Infection: clinical suspicion of infection, cultures.
Rheumatoid arthritis: small joint involvement, positive rheumatoid factor. It is often difficult to distinguish PMR from the onset of RA in older patients in whom constitutional symptoms and morning stiffness often surpass joint manifestations. However, features that support the diagnosis of PMR include a negative RF, lack of involvement of the small joints of the hands and feet, lack of development of joint damage or erosions during follow up.
Treatment: Range of motion exercises especially where muscle atrophy and/or contracture have occurred. Prednisone in a dose of 10-20 mg/day usually evokes a dramatic and rapid response. Most patients are significantly better within 1-2 days, though others may take a few more days to respond completely. The dose is reduced every 2-4 weeks using the patients response as the most reliable parameter to follow. The ESR should steadily decline, although normalization may take several weeks. Dosage is decreased by 2.5 mg increments until a dose of 10 mg per day is attained. Further tapering is by 1 mg increments as the patients and ESR are monitored. NSAIDs may be added to glucocorticoid therapy to facilitate steroid tapering.
Course: The course of PMR is longer and recurrences more frequent than once believed. Some patients may continue to be on steroids for 2-10 years. Relapses may occur in some patients (20%) after corticosteroids have been stopped and may occur months or years later. The ESR may not be as high as with the original presentation.

Summary: Site: bilateral pain and stiffness involving two of three areas (neck, shoulder girdle or hip girdle) for at least 1 month. The ESR is characteristically more than 40 but may be normal or only mildly elevated. Stiffness and pain are usually insidious in onset, symmetric and profound. However, at times, the onset is abrupt or the initial symptoms are unilateral and then progress to bilateral symmetric involvement. The shoulder is often the first area to be affected and a single area may be the predominant source of pain. Severity of condition: The magnitude of the pain limits mobility. Pain at night is common. Stiffness and gelling phenomena are dramatic. Aggravating factors: moving in bed may awaken the patient.

Case 9:
A 72-year old lady has felt non-specifically well for about 2 months. She feels stiff especially in the morning. She is unable to get out of bed by herself and has difficulty lifting her hand to comb her hair. She has also noticed pain in her knees and fingers. She had lost 5kg in weight and has developed night sweats. In the last few days she had suffered from a constant severe headache with pain in her jaw when chewing. She has previously been fit with no significant past medical history. She lives alone. She neither smokes nor drinks alcohol. She is taking no regular medication other than occasional paracetamol which has not helped her headache.
Examination: She is markedly tender to palpation over parts of the scalp; cardiovascular, respiratory and abdominal systems: normal; power is reduced in the proximal muscles of her arms and legs, but neurological examination is otherwise unrevealing.
Labs: Hb 10.2; WBC 13.2 (3.5-11.0); Plat 376; ESR 90; Na, K, crea, glucose, alb, bilirubin: normal; ALT 85 (5-35); ALP 465 (30-300); CK 134 (25-195).
Diagnosis:
Polymyalgia rheumatica/temporal arteritis
Notes:
The onset of symptoms is often dramatic. Patients may present primarily with polymyalgia type symptoms (proximal muscle pain and stiffness) or temporal arteritis symptoms (severe headaches with tenderness over the arteries involved). In polymyalgia, the muscle pain and stiffness may simulate muscle weakness but CK is normal unlike polymyositis.
Patients may have systemic symptoms such as general malaise, weight loss and night sweats. Characteristically, the ESR is very elevated and there is a mild anemia and leucocytosis. The liver enzymes are often slightly raised.
The disease usually occurs in patients over 65 years of age. The diagnosis of this condition is essentially a clinical diagnosis. A very elevated ESR is useful. A temporal artery biopsy should be performed. However, the histology may be normal because the vessel involvement with inflammation is patchy. Nevertheless, a positive result provides reassurance about the diagnosis and the need for long-term steroids.
Patients with temporal arteritis are at risk of irreversible visual loss either due to ischemic damage to the ciliary arteries causing optic neuritis or central retinal artery occlusion. The patient should immediately be started on high-dose prednsilone (before the biopsy result is available). The steroid dose should be slowly tapered according to the clinical features and ESR.

Causes of proximal muscle weakness and pain or stiffness:
1.Polymyositis
2.Polymyalgia rheumatica
3.Hypothyroidism/hyperthyroidism
4.Osteomalacia
5.Parkinsonism

 

8. HYPERMOBILITY SYNDROME (HMS)

Patients often have symptoms and signs that are frequently diffuse, chronic, and inconsistent with observed pathology. Musculoskeletal signs seen in individuals with hypermobility syndrome include recurrent traumatic conditions, arthralgias, recurrent synovitis, soft tissue rheumatism, flat feet, synovitis, juvenile episodic synovitis. Congenital hip dislocation may be present.
Although sprains, subluxations, and dislocations are more common in people with HMS, the amount of tissue damage occurring with these acute injuries may actually be decreased due to the increased laxity of joint structures.
Other findings include nerve compression disorders as carpal tunnel tarsal tunnel, acroparesthesias in multiple limbs, thoracic outlet syndrome, anxiety (70%), fibromyalgia (90%), mitral valve prolapse (3 times more prevalent in patients with HMS), Raynaud’s phenomenon, uterine prolapse, rectal prolapse, abdominal hernias, varicose veins.
 

9. STIFFMAN SYNDROME
 

Stiffman syndrome affects adult males. A prodromal phase of aching and tightness of the axial muscles progresses to symmetrical continuous stiffness of the rest of the skeletal muscles. Painful muscular spasms may be superimposed and may be precipitated by movement. Cause: overactivity in a central noradrenaline neuronal system possibly due to an autoimmune cause. Treatment: diazepam, baclofen, clonazepam, Na valproate.
 

10. TIETZE’S SYNDROME AND COSTOCHONDRITIS
 

Both of these disorders are characterized by inflammation of one or more costal cartilages at the costochondral junction but the less common Tietze’s syndrome is associated with local swelling while costochondritis is not. The cause is unknown but violent or direct trauma may play a role.
In Tietze’s syndrome, one or more tender lumps of the upper costal cartilages gradually develop, the second and the third being the most commonly affected. Deep breathing and coughing may produce local pain. The lumps are firm, tender but not warm. The course is variable; there may be spontaneous remission or painless lumps may persist for years. If pain is troublesome, local injection of lignocaine and/or corticosteroid preparations may give relief.
The diffuse nature of costochondritis and its occurrence in an older age group makes it more likely that it will be confused with visceral pain. It is too diffuse to inject but antiinflammatory drugs are often effective. Differential diagnosis includes sepsis or rheumatoid arthritis affecting the manubriosternal joint.

 

PSYCHIATRIC DISORDERS
 

Compared with the general population prevalence studies, patients attending pain, rheumatology and fibromyalgia clinics have an increased incidence (3 fold) of psychiatric diagnoses. One-sixth of subjects with chronic widespread pain have been found to have a mental disorder when assessed by a trained psychiatrist using standardized internationally accepted criteria and a structured psychiatric interview.
General clinical experience suggests that patients with a predominant psychiatric or psychologic problem have an obsession with pain that is always severe, described with many bizarre or unusual words, resistant to any form of therapy, and sometimes involving unusual sites such as the sexual organs. Symptoms and tender points (TPs) lack consistency among these patients. It is recommended that patients suspected of having a significant psychiatric problem should be evaluated by a psychiatrist. Patients who are sore literally everywhere when touched are likely to have a significant or predominant psychiatric condition, although no data exist to support this notion.
Subjects can be classified as having chronic widespread pain using the criteria for this component of the fibromyalgia syndrome as defined by the ACR: pain must have been present for >3 months in at least 2 contralateral quadrants and in the axial skeleton.
Although many psychiatric diagnoses have been associated with chronic pain, yet, certain diagnostic groups have predominated. These include mood disorders (depression and dysthymia), anxiety disorders and somatoform disorders. Other less common disorders include adjustment disorders, alcohol abuse and neurasthenia.
The 12-item version of the General Health Questionnaire (GHQ-12) is a suitable screening method that can be used to identify potential cases of mental illness in patients with chronic widespread pain. Those who score less than 2 are unlikely to have a mental disorder.
 

PSYCHIATRIC DISORDERS INCLUDE:
1. DEPRESSION
2. ANXIETY
3. ADJUSTMENT DISORDER
4. SOMATOFORM DISORDER
 

1. DEPRESSION

The essential feature of a depressive syndrome is either a dysphoric mood or a loss of pleasure or interest in usual activities. This mood disturbance is prominent and persistent. It is accompanied by a number of typical symptoms and signs of a depressive syndrome including changes in appetite or weight (typically decrease, rarely increase), disruption of normal sleep patterns (typically insomnia, rarely hypersomnia), decreased level of activity, lack of interest in sexual activity, fatigue, feelings and thoughts of worthlessness and excessive guilt, cognitive impairment (cannot concentrate or think clearly) and thoughts of death (some wish for death or long to be reunited with a deceased loved one, plans for death are formulated, some make wills, some plan suicide)
Screening for depression can be done using the Hamilton Rating Scale for Depression (HAM-D).
 

2. ANXIETY

Anxiety is abnormal fear that is out of proportion to any external stimulus. Significant anxiety is experienced by 10-15% of general medical outpatients and 10% of inpatients. Of the healthy population, 25% of individuals are anxious at some time in their lives; about 7.5% of these have a diagnosable anxiety disorder during a given month.
Diagnostic categories of anxiety include panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, phobias and primary psychiatric disorders.
Signs and symptoms of anxiety include psychological symptoms (apprehension, anticipation of misfortune, irritability, fatigue, insomnia, predisposition to accidents, de-realization in the sense that the world seems strange or unreal, depersonalization in the sense that the patient feels unreal or changed and difficulty concentrating), somatic complaints (headache, dizziness and lightheadedness, dry mouth, lump in the throat, palpitations and chest pain, shortness of breath, stomach upset and diarrhea, frequent urination, motor tension or restlessness and paresthesias) and physical signs (trembling, easy startling, hyper-reflexia, tachycardia, flushing and pallor, diaphoresis and cool, clammy skin).
Screening patients for anxiety disorder can be done using the Hamilton Rating Scale for Anxiety.
 

3. ADJUSTMENT DISORDERS

Adjustment disorders are characterized by the development of emotional or behavioral symptoms in the context of one or more identified psychosocial stressors. The resultant symptomatology is deemed to be clinically significant by virtue of either impairment in social, occupational or educational function, or the subjective experience of distress in excess of what would normally be expected for the given stressors. The stressors are more often everyday events as change of employment or financial situation rather than rare, catastrophic events as natural disasters and violent crimes. The symptomatology must, by definition occur within 3 months of the occurrence of the stressor, and must remit within 6 months following the cessation of the stressor.
 

4. SOMATOFORM DISORDERS
 

Somatoform disorders are disorders that present with physical symptoms in the absence of clear physical etiology. The symptoms of somatoform disorders are not under voluntary control nor is the patient aware of possible gains derived. The diagnosis of somatoform disorders (particularly somatization disorder) is uncommon the general population but has been prominent in some reports of chronic pain patients attending clinics.
Somatoform disorders include somatization, conversion, somatoform pain disorder, hypochondriasis and body dysmorphic disorder. Also discussed in this category are disorders related to somatoform disorders.
 

A. SOMATIZATION DISORDER: presents with a history of recurrent multiple physical complaints of several years’ duration, beginning before the age of 30 years, generally in adolescence. The description of the symptoms may often be vague, but the presentation is often dramatic. Despite multiple complaints, less than 10% of fibromyalgia patients satisfy the criteria for somatization disorder by structured interview studies. Symptoms involve complaints in many organ systems, including:
Conversion symptoms (paralysis or weakness, fainting or other loss of consciousness, seizures, stiffness, blurred vision and double vision, blindness, difficulty in swallowing, loss of voice, urine retention and difficulty in urinating)
Pain (ill-defined in joints, extremities, back)
Cardiopulmonary symptoms (shortness of breath, palpitations, chest pains, dizziness)
Menstrual symptoms (pain, irregularity, excessive bleeding)
Gastrointestinal symptoms (food intolerance, nausea and vomiting, abdominal pain, diarrhea and bloating)
Psychosexual symptoms (lack of sexual drive, lack of pleasure during intercourse, pain during intercourse).
Treatment: General principles of treatment include regular appointments so that the patient is assured of an ongoing supportive relationship with the physician, consolidation of care with one physician to minimize medications and diagnostic evaluations, avoidance of habit-forming medications and appropriate evaluation of new symptoms when they do occur as patients with somatization disorder are still at risk for organic illness

B. CONVERSION DISORDER: Conversion disorder involves the unconscious “conversion” of a psychological conflict into a loss of physical functioning, which suggests a neurologic disease. The symptom is temporally related to a psychosocial stressor. The five Ss of conversion disorder: stress, sensory-motor symptoms (pseudoneurologic as blindness, paralysis, parasthesias and seizures), significant other (the patient identifies with someone who has a similar symptom, which is due to an organic neurologic illness), secondary gains (for example, the patient is cared for by others and may avoid unpleasant duties) and symbolic nature of symptom (although the symptom may be symbolic (e.g., an arm becomes paralyzed because the patient has an unconscious wish to strike out), symbolism may be difficult to uncover).
Treatment: Stressful events evaluated. Confronting the patient with the fact that the symptoms are psychologically based is not helpful. While some patients come to understand the symbolic aspect of the symptom and gain conscious mastery of the conflict, most patients are receptive to the explanation that the disorder is a reaction to stress and to reassurance that the condition will resolve over time. These interventions may allow the patient to let go of symptoms without losing face.

C. SOMATOFORM PAIN DISORDER (synonymous with chronic pain syndrome or psychogenic pain): The patient complains of pain for which there is no demonstrable physical cause or that is excessive given the known organic pathology. Generally, this disorder results in significant impairment and inability to function. To be qualified for this diagnosis, the symptom must be present for at least 6-months.
Treatment: Antidepressants: Fifty to sixty percent of patients report an improvement in sleep, sense of well-being, and pain perception with tricyclic antidepressants. These effects occur shortly after starting treatment and on lower doses (50—100 mg) than required for the treatment of depression. Responsiveness to antidepressants is independent of overt symptoms of depression.

D. HYPOCHONDRIASIS: Patients are chronically preoccupied with fears that they have an illness despite thorough evaluation and reassurance from the physician that no organic problems can be found.
Normal physical sensations, such as sweating and bowel movements, are misinterpreted, and minor ailments, such as cough or backache, are exaggerated.
“Physician shopping” is common and is a frustration for both the patient and physician. Anxious and depressed mood, as well as obsessive-compulsive features are commonly observed. In general, these patients do not accept the idea that this is a psychiatric disorder. Usual age of onset is 20-30 years of age, but patients most commonly present to the physician in their forties and fifties. Treatment: It is not helpful to tell the patient that his or her problems are psychologically caused. The fact that the patient is concerned and desires assistance should be acknowledged early in treatment. Regular follow-up appointments legitimize the patient’s need to be sick. It may be necessary to prescribe medication; however, the patient should be told that it will only help and not “cure” the ailment. Narcotics and other habit-forming drugs should not be prescribed in order to preclude addiction.

E. BODY DYSMORPHIC DISORDER: The hallmark of this disorder is preoccupation with some imagined defect in the body, usually of the face. There is usually a history of frequent visits to doctors, especially dermatologists or plastic surgeons. Depressive mood and obsessive-compulsive traits are common.
Treatment: tricyclic antidepressants, antipsychotic agents, and psychotherapy can be considered.

DISORDERS RELATED TO SOMATOFORM DISORDERS
Factitious disorders
Malingering

A. FACTITIOUS DISORDER: Patients are in voluntary control of their symptoms of physical illness in that, although their behavior is deliberate; what precipitates this behavior is not.
Symptoms may range from complaints of pain when patients feel no pain to self-inflicted infection, such as that arising from self-injection with feces or saliva, which can develop into life-threatening illness. The medical knowledge of patients is often highly sophisticate. There may have been an experience with a physician in early life either through a family relationship or through illness. A significant proportion of these patients are emp1oyed in the health care field as paraprofessionals.
By complaining of bizarre or unusual symptoms, patients may encourage invasive diagnostic procedures, such as laparotomy and angiography. Patients may lie about any aspect of their history with a dramatic flair (pseudologia fantastica). Narcotic abuse and addiction are associated findings in about one-half of these patients.
History: Upon hospital admission, patient behavior is disruptive and demanding. Symptoms change as workups prove negative. Eventually, patients are confronted with evidence of faking, and they usually react angrily and leave against medical advice. This pattern of behavior can become chronic and involve multiple admissions to different hospitals, and it is then called Munchausen syndrome. Other names for factitious disorder with physical symptoms include polysurgical addiction, hospital hoboes and hospital addiction. Treatment: Until the patient is willing to face the fact that he or she has a psychiatric illness and agrees to psychiatric hospitalization or treatment, the prognosis is likely to be poor. The patient should be confronted in a calm, non-condemning manner, and the cost of the illness emotionally as well as financially should be discussed.

B. MALINGERING: Malingering is not considered a mental disorder. Malingering individuals willfully and deliberately fake or exaggerate illness with the conscious intent to deceive others. Their reasons for faking illness (e.g., monetary and legal concerns) can be understood by examining the circumstances affecting these individuals rather than their psychological makeup. Individuals are often evasive and uncooperative upon examination, and there is a marked discrepancy between their claimed disability and the physical findings. Individuals who malinger may have an antisocial personality disorder. Treatment: not considered an illness, there is no medical or psychiatric treatment.

Nonorganic signs of LBP that indicate the need for a detailed psychological evaluation:
Tenderness: superficial, non-anatomic.
Stimulation: axial loading, rotation.
Distraction: straight leg raising.
Regional: weakness, sensory.
Overreaction.
Waddell G, McCulloch JA, Kummel E et al. Nonorganic physical signs in low back pain. Spine. 5:117-125, 1980.

Note:
Infrequently the clinician sees a child or adolescent with leg pain without any distinguishing features; psychogenic factors may have to be considered. The clinician should then look for the following: Death of a parent or separation from a significant other person, marital discord between the parents, family history or similar complaints of pain in parents or siblings, difficulty in school with academic subjects, teachers or peers.

 

OTHER DISORDERS
 

1.VIRAL HEPATITIS
2.CONNECTIVE TISSUE DISEASES AND RELATED DISORDERS:
3.MUSCLE DISEASE:
4.MALIGNANCIES
5. DRUG RELATED
6.PERIPHERAL ARTERIAL VASCULAR DISEASE
7. GROWING PAINS
8. NUTRIONAL DEFICIENCY
9. ACNE ARTHRALGIA
10.PARKINSON’S DISEASE.
11.SICKLE CELL DISEASE


 

1.VIRAL HEPATITIS
 

HEPATITIS C INFECTION (HCV): A by-product of increasing experience with patients infected with the hepatitis C virus is the awareness of a variety of extrahepatic syndromes that seem to be associated with HCV infection (Killenberg, 2000). Of these, musculoskeletal affection is of particular importance to practicing rheumatologists. Indeed, a wide range of musculoskeletal manifestations has been reported to occur in patients with chronic hepatitis C infection. It includes arthralgia, myalgia, back and neck pain, pain all over with morning stiffness. Musculoskeletal pain and fatigue are not related to levels of aminotransferases, liver disease severity on biopsy or interferon treatment.
Many authors recommend that HCV infection should be included in the differential diagnosis of patients presenting with unexplained rheumatological symptoms (Lee et al, 1998). In 1999, Rivera et al tried to define the clinical features of arthritis in patients with chronic HCV infection. Unfortunately, they did not find a single clinical picture of arthritis in the HCV patients studied. Nevertheless, they found a well-defined picture of arthritis associated with the presence of mixed cryoglobulinemia in HCV infected patients. This consists of an intermittent, mono or oligoarticular, nondestructive arthritis affecting large and medium sized joints.
Barkhuizen et al studied the frequency of fatigue and musculoskeletal pain in HCV infected patients and compared it to the frequency of their occurrence in patients with other chronic liver diseases as hepatitis B infection and alcoholic liver disease. In 239 patients with chronic HCV studied, musculoskeletal pain was present in 70% and fatigue in 56%. Concerning the pain, back pain was the most common complaint (54%), followed by morning stiffness (45%), arthralgia (42%), myalgia (38%), neck pain (33%), pain all over (21%) and subjective joint swelling (20%). Musculoskeletal pain and fatigue were more frequent among patients with isolated HCV infection than among patients with isolated hepatitis B infection or alcoholic liver disease and were not related to levels of aminotransferases, liver disease severity on biopsy or interferon treatment.
Lee et al also studied the rheumatological manifestations in patients with chronic HCV infection and investigated the possible association between these manifestations and the presence of cryoglobulinemia. In 49 patients studied, they found that the most common manifestations related to rheumatic disorders were as follows: parasthesias (44%), cutaneous manifestations (37%), arthralgias / arthritis (35%), oral ulcers (33%), dry eyes (22%), abdominal pain (14%), dry mouth (10%) and Raynaud’s phenomenon (8%). Cryoglobulinemia was detected in the serum of 29 patients out of the 49 and type III was the cryoglobulin type identified in 23 out of the 29 patients. They did not find any difference in the HCV genotype nor in the rheumatological manifestations between patients with and patients without cryoglobulinemia.
The cryoglobulinemia syndrome that is associated with HCV infection has been the subject of extensive research in the recent years. It is the most documented extrahepatic manifestation of hepatitis C virus infection. Peripheral neuropathy is present in most of the patients with symptomatic cryoglobulinemia where it may be the first clinical manifestation of the disease. In one study, it was found that the presence of peripheral neuropathy in cryoglobulinemic patients was significantly associated with older age, higher rheumatoid factor reactivity and immunoglobulin M levels and reduced complement C4 activity (Zaltron et al, 1998).
Buskila et al also studied the musculoskeletal aspects of chronic HCV in 90 Israeli patients. Rheumatic manifestations were found in 28 subjects (31%). They included myalgias (24%), fibromyalgia (16%), cryoglobulinemia (11%), arthrlagias (9%), sicca symptoms (8%), arthritis (4%), cutaneous vasculitis (2%)polymyositis (1%) and antiphospholipid syndrome (1%). Rheumatic manifestations were not related to liver disease severity or to subject’s gender. Sixty-nine percent of the patients had at least one autoantibody detected in the serum, the most common being rheumatoid factor (44%), anti-nuclear antibody (38%), IgM and IgG anticardiolipin antibodies (28% and 22% respectively). The frequency of autoantibodies was not associated with liver disease or to subject’s gender.
References:
Zaltron S, Puoti M, Liberini P, Antonino A, Zanini B, Carosi G: High prevalence of peripheral neuropathy in hepatitis C virus infected patietns with symptomatic and asymptomatic cryoglobulinemia. Ital J Gastroenterol Hepatol 30(4):391-395, Aug 1998.
Lee YH, Ji JD, Yeon JE, Byun KS, Lee CH, Song GG: Cryoglobulinemia and rheumatic manifestations in patients with hepatitis C virus infection. Ann Rheum Dis 57(12):728-731, Dec 1998.
Barkhuizen A, Rosen HR, Wolf S, Flora K, Benner K, Bennett RM: Musculoskeletal pain and fatigue are associated with chronic hepatitis C: a report of 239 hepatology clinic patients. Am J