Malignant pyoderma responding to cyclosporine

ARTICLE

A 54-year-old man attended our clinic for extensive ulcerations of the scalp and face. Over the previous 4 years, similar ulcers had developed on the retroauricular and nucal regions. On examination an irregular, deep and purulent ulcer with raised inflammatory edges was observed on the vertex area (Fig. 1). A small ulcer with a necrotic base was also present on the left temple, and pustules, abrasions and small ulcerations extended from the right temple to the eyebrow (Fig. 2). No lymphadenopathy was noted in either the auricular, cervical, or occipital chains.

Laboratory tests disclosed increased erythrocyte sedimentation rate (ESR) and reactive C protein (RCP), normal titers of antinuclear (ANA) and antineutrophil cytoplasmic antibodies (ANCA), and normal complement levels. Chest X-ray, serum angiotensin-converting enzyme level, calcemia and calciuria were within normal limits. A Mantoux test, the search for Leishmania and Mycobacteria by direct smear and culture, as well as the sero-immunologic diagnostics failed to demonstrate a specific aetiology. A bacterial culture from the scalp showed the presence of rare colonies of non-aureus Staphylococcus, while fungus cultures were negative.

A first histologic examination, performed on the vertex ulceration, demonstrated acanthosis and a lymphohistiocytic and neutrophilic infiltrate, mainly distributed in the perivascular, periadnexal and interstitial dermis. Specific stains for the search of micro-organisms were negative. A second histologic examination from a recent nodular lesion of the nape showed a granulomatous-suppurative folliculitis with foreign-body giant cells (Fig. 3).

After having excluded infectious granulomas (tuberculosis, leishmaniasis, atypical mycobacterial and fungal infections), sarcoidosis and Wegener's granulomatosis, a diagnosis of malignant pyoderma was suggested. During hospitalization, the patient was started on methylprednisolone (250 mg/day pulse therapy e.v. for three days, then tapered) and dapsone (100 mg/day). After 2 weeks the patient was discharged on oral dapsone. Since no clinical improvement was obtained after one month, such therapy was replaced by cyclosporine (from 4 to 2.5 mg/Kg/day), leading to complete remission in 6 months.

Comments

Pyoderma gangrenosum (PG) is an ulcerative skin disorder usually associated with an underlying systemic disease such as ulcerative colitis and polycythemia vera [1]. The most common sites are the lower extremities. Head and neck involvement is rare, but possibly more common than once thought. The term of malignant pyoderma (MP) was firstly used by Perry et al. [2] to describe a subtype of PG with differential features that can be summarized as follows: 1. young male predominance [3, 4]; 2. peculiar localization to the cephalic extremity with a predilection for the preauricular region [5]; 3. absence of ulcer undermining and surrounding erythema; 4. rapid evolution of initial papulopustular or nodular lesions into destructive ulcers; 5. lack of associated systemic illness, 6. histopathological findings represented by polymorphonuclear cells infiltrating the hair follicle with a tendency to form giant cell granulomas [2]; 7. chronic course and resistance to therapeutical attempts.

The term "malignant" usually indicates neoplastic processes of the skin and seems hardly appropriate to an inflammatory dermatosis. In the case of cephalic pyoderma however, the adjective has been repeatedly adopted in the literature to highlight the severe evolution of the lesions that rapidly enlarge and deepen involving wide areas. The course is in fact chronic with relapses. Even if systemic diseases are not found in association with MP, neurological disturbances, such as transient cranial nerve palsies, unilateral sensorimotor loss and mental confusion, have been described in cases reported by Wernikoff [3]. The cause of MP is unknown. Most authors agree it is noninfectious, because of negative cultures and lack of response to antibiotics, as observed in our case. Sometimes, as in classic PG, a postraumatic development of MP lesions has been hypothesized [4].

Regarding therapy, high doses of systemic corticosteroids generally improve the disease which usually recurs with lowering of the doses. Other drugs reported as effective include by dapsone [4, 6], azathioprine and clofazimine [7] in combination with corticosteroids. In our patient, no improvement could be obtained with corticosteroids and dapsone, while treatment with cyclosporine led to remission of the skin lesions. Numerous reports in the literature suggest cyclosporine as one of the first-line drugs in the treatment of PG [8-11] and our data indicate that it can be successfully used also for MP.

References

1. Yco MS, Warnock GR, Cruickshank JC, Burnett JR. Pyoderma gangrenosum involving the head and neck. Laryngoscope 1988; 98: 765-8.

2. Perry HO, Winkelmann RK, Muller SA, Kierland RR. Malignant pyoderma. Arch Dermatol 1968; 98: 561-74.

3. Wernikoff S, Merritt C, Briggaman RA, Woodley DT. Malignant pyoderma or pyoderma gangrenosum of the head and neck? Arch Dermatol 1987; 123: 371-5.

4. Anadolu R, Piskin G, Gurgey E. Malignant pyoderma: a clinical variant of pyoderma gangrenosum. Int J Dermatol 1996; 35: 811-3.

5. Dicken CH. Malignant pyoderma. J Am Acad Dermatol 1985; 13: 1021-5.

6. Micali G, Cook B, Ronan S, Yadgir J, Solomon LM. Cephalic pyoderma gangrenosum (PG)-like lesions as a presenting sign of Wegener's granulomatosis. Int J Dermatol 1994; 33: 477-80.

7. Pari T, George S, Jacob M, Chandi SM, Pulimood S, Rajagopalan B. Malignant pyoderma responding to clofazimine. Int J Dermatol 1996; 35: 757-8.

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9. Capella GL, Frigerio E, Fracchiolla C, Altomare G. The simultaneous treatment of inflammatory bowel diseases and associated pyoderma gangrenosum with oral cyclosporin A. Scand J Gastroenterol 1999; 34: 220-1.

10. Matis WL, Ellis CN, Griffiths CEM, Lazarus GS. Treatment of pyoderma gangrenosum with cyclosporin. Clin Res 1991; 39: 507-10.

11. Planaguma M, Puig LL, Patos VG, Alomar R, Pujol R, De Moragas JM. Pioderma gangrenoso. Respuesta al tratamiento con ciclosporina A en una serie de cinco casos. Actas Dermo-Sifilog 1992; 83: 68-72.