A 21-year-old male mechanic presented in 10/2000 with an acute onset of erythema of the face together with painful skin lesions on the shoulders, back and front of the chest. He was admitted to  a hospital in his area where he was diagnosed as a case of SLE  on the basis of a malar rash,  photosensitivity and positive ANA and anti-DNA lab tests. He was started on a dose of 25mg of prednisolone (that was to be tapered soon to 10mg).

Four months later (2/2001), he started to complain of excessive falling of hair that was associated with recurrent attacks of painless oral ulcers.

And another four months later (6/2001), he started to suffer from ulcers all over the scalp and was re-admitted to the hospital were investigations revealed evidence of renal affection and a renal biopsy (done in 10/2001) showed class III lupus nephritis with mild tubulointerstitial nephritis. Activity index 5/24 and chronicity index 1/12.

Rash over scalp (1)

Rash over scalp (2)

The patient was told by other patients admitted with him in the ward that he had a total loss of memory for 1 day.

In 11/2001, he was first seen by us at Kasr Elaini (Cairo University Hospital) where he was admitted. His main complaints at that time were the facial erythema and the skin ulcers.

Examination revealed:

Vital signs: normal;

Chest, heart, nervous system, ENT: NAD;

Abdomen: protuberant abdomen; no organomegaly

The only remarkable positive findings were on mucocutaneous examination;

He had

1. A malar rash and ulcerative lesions on anterior chest that were no longer painful and were partially healed leaving atrophic scars behind.

2. Diffuse alopecia sparing the occipital scalp. Painful ulcerative lesions of the scalp with necrotic base. Local antibiotic cream had been applied to active lesions with no improvement.

3. Healed ulcerative lesions over the shoulders, upper arms and back of trunk

4. Multiple painful and very tender subcutaneous swellings initially diagnosed as lupus panniculitis.

Malar rash

& anterior chest wall lesions

Healed lesions over shoulder and trunk

Diffuse alopecia sparing scalp

Scalp lesions

Rash over anterior chest wall

Labs: ESR 88; Hb 11.3; WBC 2.8 Differential: neut 24, ly 72 (moderate absolute neutropenia); plat 233; urine: ++ albumin and hyaline casts; 24 hr urinary albumin 1.7gm; crea clearance 76ml/min; ALT 38 (41); AST 37 (38); ALP 140 (240)

Medications: He was on 30mg of prednisolone, insulin mixtard 15U/-/10U for steroid-induced diabetes mellitus, K permanganate and garamycin ointment for the skin lesions.

At that time, the ACR SLE criteria he fulfilled were:

Malar rash

Photosensitivity

Oral ulcers

Class III lupus nephritis

Amnesia

Neutropenia

Positive antinuclear antibody

Positive anti-DNA

A skin biopsy in 11/2001 revealed lipodermatosclerosis (this term describes the pathological finding and is not a clinical diagnosis).

Differential diagnosis of ulcerative skin lesions in a patient with SLE:

Vasculitic ulcers

Pyoderma gangrenosum

Pressure sores

Infection

Vasculitic ulcers:

Most frequently located about the malleoli. They are punched out lesions that are exquisitely tender. Sometimes they may precede the recognition of SLE by many years.

Pyoderma gangrenosum:

A rare ulcerating lesion of unknown cause.

Manifests as a painful single ulcer in the lower extremities, buttock or abdomen developing sometimes at sites of previous minor trauma.

Pressure sores:

Sites of pressure in bed-ridden patients.

Infection:

Usually a single ulcer

DD of SC nodules in a patient with SLE:

Lupus profundus/panniculitis

Erythema nodosum

Pyoderma gangrenosum

RA nodules

LE profundus/LE panniculitis (Kaposi-Irgang disease):

A rare form of cutaneous lupus typified by inflammatory lesions in the lower dermis and subcutaneous tissue.

Typical subcutaneous lesions present as firm nodules, 1 to 3 cm in diameter. The overlying skin often becomes attached to the subcutaneous nodules and is drawn inward to produce deep, saucerized depressions. The head, proximal upper arms, chest, back, breasts, buttocks, and thighs are the sites frequently affected.

Erythema nodosum:

Tender lesions that are red or violet subcutaneous nodules, 1-5 cm in diameter.

They usually develop in pretibial locations and resolve spontaneously over several weeks without ulceration or scarring. The lesions may develop less frequently on the thighs, arms, face, neck and trunk.

Pyoderma gangernosum:

Very rarely, pyoderma gangrenosum starts as SC nodules that break down to form deep ulcers.

Rheumatoid nodules:

Rheumatoid subcutaneous nodules may also be seen in a small portion of patients with lupus.

They are firm and non tender. Size is 0.5-4 cm in diameter. May be movable or fixed to perisosteum or deep fascia.

Our patient was diagnosed as a case of pyoderma gangrenosum based on the characteristic clinical features.

In 11/2001, he was started on a regimen of monthly pulses of cyclophosphamide 800mg each (for the renal lupus and the PG lesions) for 6 months to be spaced to 3-monthly intervals for 2 years. By the fourth month of cyclophosphamide therapy, the skin lesions had resolved completely to leave deep atrophic scars.

Pyoderma Gangrenosum

Pyoderma gangernosum (PG) is a rare destructive inflammatory skin disease that may start either in the absence of any underlying disorder (idiopathic PG) or in association with systemic disease. Common disease associations include ulcerative colitis and Crohn’s disease, myeloid leukemia, IgA gammopathy and  Takayasu arteritis. Less common and rare disease associations include multiple myeloma, rheumatoid arthritis, Wegener’s granulomatosis and systemic lupus erythematosus (Olson, 1971) and Behcet’s disease.

Clinical manifestations:

The salient feature of PG is an ulcer with a raised inflammatory border and a boggy necrotic base.

It starts as a deep seated painful nodule or as a superficial hemorrhagic pustule either de novo or after minimal trauma.

Rarely, PG may start in the subcutaneous fat, presenting as an extremely painful suppurative panniculitis. Breakdown of the lesion and the centrifugal spread of the resulting ulcer will eventually reveal the true nature of the process.

The ulcerating lesions discharge a purulent and hemorrhagic exudate; the irregular crenated border is elevated and is dusky red or purplish; it is undermined, soggy, and often perforated so that pressure releases pus both into the ulcer and through these openings.

Multiple lesions arising simultaneously or consecutively in different parts of the body also occur.

Lesions are usually solitary but may arise in clusters, which then coalesce to form multi-centric irregular ulcerations.

Superficial ulcers may be confined to the dermis, but they often extend to the fat and even down to the fascia.

PG may occur at any age.

PG lesions are almost invariably painful.

Any area of the body may be involved. Although mucous membranes are usually spared, aphthous lesions may occur in the oral mucosa; massive ulcerative involvement of the oral cavity, larynx and pharynx, vulva and eyes have occasionally been observed.

A halo of bright erythema surrounds the margin of an advancing ulceration which may expand rapidly in one direction and more slowly in another, so that a serpignous configuration results.

Peripheral growth results from the burrowing extension of undermined margin or from new hemorrhagic pustules arising on the border. The base of such an ulcer is partially covered with necrotic material and partially studded with small abscesses.

The clinical course may present two patterns:

Explosive onset and rapid spread of lesions: this type is characterized by pain, toxicity and fever, hemorrhagic blisters and suppuration, extensive necrosis and soggy ulcer margins with a highly inflammatory halo.

Indolent and slow form: exhibits massive granulation within the ulcer from the onset, crusting and even hyperkeratosis at the margins. It spreads slowly grazing over large areas of the body for months and is characterized by spontaneous regression and healing in one area and progression in another. In both forms, healing occurs spontaneously at some time during the disease process resulting in thin atrophic usually cribriform scars.

Laboratory findings:

There are no specific diagnostic laboratory findings.

A high ESR, leucocytosis and elevated CRP are invariably present. There may be anemia and low serum iron.

Pathology:

The neutrophil is the cytologic hallmark of the PG. Indeed PG responds to sulfa drugs, which have an anti-neutrophilic action and PG has been observed to occur as a side effect of treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) (Johnson and Grimwood, 1994).

Histologic features are not diagnostic. They encompass edema, neutrophilic infiltration, thrombosis, necrosis and abscess formation that eventually regress with prominent fibroplasias (Harwitz and Haseman, 1993).

Treatment of PG:

Idiopathic PG is treated with systemic corticosteroids, sulfa drugs (as dapsone, sulfasalazine), cyclosporine, clofazimine. Adjunctive topical treatments as intra-lesional steroids and topical cyclosporine have been tried. However, in patients with an underlying disease who happen to be the type of patients we are likely to encounter in rheumatologic practice, therapy should be directed primarily to the cause and not only (or even not at all) to PG. 

Conclusion:

PG is a rare but serious disorder that can be associated with systemic lupus erythematosus. It may present atypically with painful subcutaneous nodules, as was the case with our patient, thus leading to the misdiagnosis of the more benign disorder, lupus panniculitis. It is managed successively with IV cyclophosphamide.