SkIndia Quiz 21: Recurrent papulonodular lesions on elbows, fingers and lower leg.

A 35-year-old human immunodeficiency virus (HIV)-negative female patient presented with smooth surfaced umbilicated papulo-nodules of variable sizes of 3 years duration. The lesions were distributed over the extensor aspects of elbows, knuckles, dorsum of fingers and over medial malleolus of left leg [Figure 1]. They progressively increased in size to attain the present status. The lesions were asymptomatic but she complained of occasional sensation of numbness and pain over the fingers; in winter season as well as, on exposure to cold water. The lesions over the right elbow showed evidence of ulceration. She did not complain of any joint pain and had no ocular complaints, sore throat, fever or any constitutional symptoms. Fingernails showed features consistent with distal lateral subungual onychomycosis. There was no history of skin tightening or malar rash. There was neither any sensory loss nor history of similar lesions elsewhere. Past history revealed the occurence of similar lesions many years ago, which responded to pharmacotherapy with dapsone. The lesions used to resolve with atrophic scarring, without any pigmentation. Family history was non-contributory. Systemic examination was unremarkable. Laboratory investigations showed a high absolute eosinophil count of 11,500, with the rest of the hemogram being normal. Urea, creatinine, urinalysis, serum calcium (9.7 g/dl), uric acid (3.2 mg/dl) were all within the normal range. However, alkaline phosphatase (250 IU/L) and serum lactate dehydrogenase (766 IU/L) were raised. Anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, anti-scl 70 antibody, anti-streptolysin O titers, venereal disease research laboratory test, C-reactive protein, rheumatoid factor, slit-skin smear examination, Mantoux test and chest X-ray, were normal. Ultrasonography of abdomen and color doppler of the arterial system of the upper limbs were normal. Bone marrow examination showed eosinophilic myelocyte and metamyelocyte, increased mature eosinophils with blasts lesser than 5% and mild megaloblastoid changes. Histopathology of a nodular lesion showed leukocytoclastic vasculitis and fibrinoid degeneration and neutrophilic infiltrate and fibrosis in the dermis [Figure 2].

Figure 1

Smooth surfaced firm umbilicated papulo-nodules of variable sizes, distributed over the extensor aspects of both elbows (a), knuckles, dorsum of fingers (b) and over medial malleolus of left leg (c), with a close-up view of a lesion (d)

Figure 2

Photomicrograph of a representative lesion from elbow showing leukocytoclastic vasculitis, fibrinoid degeneration (arrow a) and neutrophilic infiltrate (arrow b) and fibrosis in the dermis (H and E, ×40)

ANSWER

Erythema elevatum diutinum (EED).

DISCUSSION

EED is a localized fibrosing small-vessel vasculitis predominantly affecting adults. Cutaneous lesions include asymptomatic, papulo-nodules and plaques distributed symmetrically over extensor aspects of limbs mainly over the joints, dorsal hands, feet, knees, elbows, buttocks and tendoachilles. To start with, the lesions are red to violaceous and soft, but gradually become brown to yellow colored and fibrotic, with eventual atrophic scarring. Consistent with our case, the lesions may present with umbilication and clinical differentials include papulonecrotic tuberculid, histoid leprosy, molluscum contagiosum with secondary infection, perforating dermatosis such as reactive perforating collagenosis, Gottron's papules of dermatomyositis and papular xanthoma. The etiopathogenesis of EED is not clear. It is probably an arthus-like immune complex reaction and ensuing fibrin deposition, a clinicopathological reaction pattern. Histologically, early lesions are characterized by non-specific leukocytoclastic vasculitis with some fibrin deposition and eosinophilic infiltrate in the dermis. Later on, granulation tissue formation and perivascular eosinophilic fibrosis along with an inflammatory infiltrate of macrophages, plasma cells and lymphocytes are present, suggestive of chronicity of the lesion.[1] Close clinical and histological differentials include all forms of small-vessel vasculitis, Sweet's syndrome, granuloma faciale, multicentric reticulohistiocytosis. Since EED lesions often simulate sarcoidosis, leprosy, discoid lupus erythematosus, psoriasis etc., clinicopathological correlation is quintessential. The chronic and recurrent nature of EED is the primary means of distinguishing it from entities that are clinically and histologically similar. The vascular endothelium of EED stains positive for CD31, CD34, vascular endothelial growth factor and factor VIIIa and negative for factor XIIIa and transforming growth factor-β.[2] Associations have been reported with many conditions such as autoimmune diseases (rheumatoid arthritis, celiac and inflammatory bowel disease, diabetes mellitus), infections (syphilis, Streptococcus, hepatitis, HIV infection), malignancies (multiple myeloma, B-cell lymphoma, breast carcinoma, myelodysplasia), monoclonal gammopathies, hypergammaglobulinemia, pyoderma gangrenosum, and relapsing polychondritis.[3] In a study conducted by Cherif et al., the association of EED with seronegative rheumatoid arthritis was found to be most significant.[4] Ocular involvement may present as nodular scleritis.[5] Moreover, IgA monoclonal gammopathy is also evident in many patients and some authors recommend routine immunoelectrophoresis. Dapsone shows excellent results and remains the mainstay of the treatment; but the reappearance of lesions is common on discontinuation of the drug. Other alternative treatments include sulfpyridine, colchicine, cyclophosphamide, potent topical or intralesional steroids and niacinamide. Systemic corticosteroids have not shown any good result. Treatment of the associated disease may herald the resolution of lesions of EED. HIV-associated EED responds to the introduction of antiretroviral drugs. With the diagnosis of EED, our patient has been prescribed dapsone 100 mg/day. At present, she is under follow-up with the lesions gradually diminishing in size.