Diagnosis: Gottron papules

Gottron sign consists of red-purple hypertrophic papules, atrophic erythema, or red-purple macules on the extensor surface of the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints of the hands and toes. Gottron papules (GPs) have been described as pale rose-colored to violet, slightly elevated lichenoid lesions that can impart to the skin an edematous erythema. Often, the longer GPs are present, the less erythematous and more atrophic they become.

Gottron sign is sometimes considered pathognomonic for dermatomyositis (DM), but this conception is complicated by reality because other entities can mimic GP clinically (although not clinically and histologically).
That said, GPs, along with a lilac (or heliotrope) rash over the eyelids, are among the most common skin manifestations of DM. GPs can develop in patients without muscle weakness (amyopathic dermatomyositis). Some of these patients slowly progress to develop symptomatic muscle weakness over a period of years, whereas others go for 10-20 years and longer without the appearance of muscle disease.10 Complications that can arise in amyopathic DM include progression to full-blown DM, interstitial lung disease, and adenocarcinoma.

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A variety of entities have been reported to mimic Gottron sign, including acanthosis nigricans and knuckle pads. Besides DM, perhaps the most common cause/association with GP is use of hydroxyurea. In one study of 158 patients with chronic myeloid leukemia treated with hydroxyurea, 13% presented with severe mucocutaneous changes, including 4% with papules visually indistinguishable from GPs.10 In that study, Slobodin reported that a 57-year-old white woman who received hydroxyurea for chronic myeloid leukemia developed a GP-like eruption, which histologically was a seborrheic keratosis, without any of the other clinical or laboratory signs of DM. In another review of 35 reported cases, GPs in patients treated long-term with hydroxyurea were characterized by prolonged latency of onset, slow progression, and subsequent healing after cessation of hydroxyurea. The patients had no other sign of DM and received medication for seven months to 10 years before the appearance of a GP-like eruption.

Slobodin has posited that hydroxyurea-induced GP may be due to a combination of phototoxic UV damage and cumulative cytologic damage to the basal layer and epidermis. The suggested mechanism is inhibition of DNA synthesis and repair.10

The prevalence of GP in patients with DM varies by the study. One investigation of 16 patients with juvenile DM concluded that the heliotrope rash and GPs classically associated with DM appeared less commonly than an extremity rash and periungual erythema.11 In 34 DM patients in Hungary, the characteristic heliotrope rash was observed in 26 patients; GPs in 20 patients; poikiloderma in two patients; and calcification, ulcers, or Raynaud syndrome in one patient each.

A retrospective analysis of 25 Arab patients with juvenile dermatomyositis (JDMS) found that skin lesions included GPs (15 patients [(60%]), heliotrope (13 [52%]), erythematous malar rash (8 [32%]), and pigmentary changes (12 [48%]). A German study of 32 patients with JDMS found that all suffered from vasculitic skin changes like facial erythema, often with edema, Gottron sign, telangiectasias, erythematous eruptions, different rashes, and necrotic ulcerations. A retrospective Italian study of 44 subjects affected by polymyositis/dermatomyositis (PM/DM) found dermatologic manifestations, including pink or lilac edema-erythema over the periorbital areas, wine-red maculae, Gottron sign, poikiloderma, telangiectasias, and skin vasculitis, in 86.3% of patients.

Histologically, GP resembles DM (lymphocytic, sparse, interface dermatitis) except that because of body site, GP also manifests with hyperkeratosis and papillomatosis.12 In one study of 11 patients, histologic features of GPs included basal-layer degeneration (81%), basement-membrane thickening (45%), sparse diffuse lymphocytic infiltrate (81%), and a moderate-to-dense diffuse lymphocytic infiltrate (18%). Hypergranulosis, acanthosis, mucin, and papillary dermal fibrosis have also been noted.12   

In a study that looked at immunostained skin biopsy specimens from GPs of eight DM patients, activated CD4+ Th lymphocytes manifested as the principal infiltrating cells.13 The CD4/CD8 ratio was approximately 2.5. Researchers detected a mixed Th1/Th2 profile and higher Th1 cytokine production together with significant staining for CXC chemokine receptor 3. Neutrophil granulocytes were the second most common immune cell present. Eosinophils were generally absent. The researchers concluded that “activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction between CD40 and CD40 ligand could be an important mechanism of cellular activation in cutaneous immune-mediated inflammation by induction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. There was a significant quantity of myeloperoxidase-positive cells (neutrophil granulocytes) in the inflamed tissue, and they might have a role in sustaining the chronic inflammation.” 13

Treatment of GP often involves the use of topical corticosteroids. Effective systemic treatment of the underlying DM is perhaps the most important approach to GP. Pulsed dye laser therapy has been reported, but I do not advocate it.

This patient was treated with methotrexate 10 mg weekly and topical corticosteroids. Her CK dropped into the normal range, and the skin eruption became less intense.

Dr. Scheinfeld is assistant clinical professor of dermatology at Columbia University in New York City, where he has a private practice.

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All electronic documents accessed January 12, 2009.