Scleroderma_0412 Derm Clinic
A woman, aged 38 years, complained of color loss on her cuticles and upper chest. Examination revealed bilateral puffy hands with depigmentation and dilated capillary loops of all proximal nail folds.
A sclerotic depigmented patch with circular islands of normal color was present over her mid-chest. Review of systems revealed Raynaud’s phenomenon, as well as recent onset of dyspnea on exertion. A biopsy was taken from the patch on her chest. Further studies demonstrated the presence of anti-DNA topoisomerase I (Scl-70) antibodies and a low diffusion capacity on pulmonary function testing.
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The biopsy showed a normal epidermis, thickened and closely packed collagen bundles in the reticular dermis spreading up into the papillary dermis, and atrophy of the eccrine glands; a paucity of vessels was evident. Subcutaneous fat was partially replaced by collagen bundles. Silver staining for melanocytes was negative. The diagnosis was consistent with scleroderma with vitiligo-like pigmentary changes.
The term scleroderma encompasses a spectrum of disorders caused by excessive collagen deposition. The skin is the most commonly affected organ; however, the spectrum of disease can range from an isolated skin lesion to a multiorgan systemic disease. When only localized cutaneous plaques exist, the condition is called morphea.
Morphea rarely has systemic manifestations. The term systemic sclerosis (SSc) is the preferred nomenclature when systemic manifestations exist. A very small percentage of patients may have systemic disease without cutaneous changes, which is classified as sclerosis sine scleroderma.
Systemic sclerosis is divided into two main subsets that are defined by the extent of skin involvement: diffuse systemic sclerosis (dSSc) and limited systemic sclerosis (lSSc).1 In dSSc, skin involvement is widespread, affecting the extremities, chest, abdomen and shoulders. In comparison, skin changes in lSSc are typically limited to the hands, face, feet and forearms.
Collagen deposition results in skin thickening and hardening, which is frequently preceded or accompanied by edema and erythema. Overtime the more classic sclerodactyly with skin tightening (sclerosis) is observed. Nail fold telangiectases are common but not pathognomonic for SSc, since they can also be seen in systemic lupus and dermatomyositis. The presence of Raynaud’s with or without digital infarcts is highly suggestive of the diagnosis of SSc. Cutaneous calcification is variable. CREST syndrome (Calcinosis, Raynaud’s syndrome, Esophageal dysmotility, Sclerodactyly, and Telangiectasia) is a form of lSSc. Pruritus is common in patients with advanced skin disease, and pigmentary alteration can also be seen in SSc.
More common in women, with a peak onset between age 30 and 50 years, SSc has an annual incidence of 0.6-122.0 per million persons.2 The presentation of SSc varies according to the organ of involvement and disease severity. In addition to the skin, other frequently affected organ systems include the musculoskeletal, renal, pulmonary, cardiac and GI tract.
The most frequent constitutional symptoms of individuals with SSc are fatigue, weakness, and insomnia; other symptoms reflect the organs affected and include stiffness, decreased strength, joint pain, palpitations, chest pain, shortness of breath, cough, bloating, abdominal pain, and swallowing difficulties.
The depigmentation seen in association with SSc is very uncommon. It can be morphologically identical to idiopathic vitiligo and is often mistaken for vitiligo. Although islands of normal color can be seen within patches of vitiligo (due to repigmentation), areas of pigmentary retention are uniformly seen in SSc-associated depigmentation. Anatomic sites most commonly affected are the hands, arms, upper chest, neck and face. Unlike vitiligo, which commonly affects the lips and mucosa, mucosal depigmentation has not been reported in SSc.
A biopsy of a depigmented area will demonstrate an absence of melanocytes, frequently associated with a lymphocytic infiltrate and dermal fibrosis.3 The areas where color persists in SSc are around hair follicles. This follicular sparing has been attributed to better blood circulation around hair follicles.
The underlying pathology of SSc is not fully understood but is believed to be a combination of immune system activation and vascular damage inciting existing fibroblasts to excessively produce collagen. Although the pathogenesis of SSc color loss is also poorly understood, it is thought to be similar to the pathogenesis of vitiligo. According to the autoimmune theory for vitiligo, activation of the immune system and the subsequent development of autoantibodies lead to the destruction of melanocytes. The absence of melanocytes in biopsy samples and the presence of various autoantibodies in both vitiligo and vitiligo-like macules of SSc support this theory.
When evaluating patients with skin complaints, consider a diagnosis of SSc. Although systemic involvement is more common in advanced dSSc, those with lSSc or early onset of dSSc may have serious organ involvement, as seen in this patient. Despite minimal cutaneous findings at presentation, further evaluation demonstrated the presence of significant pulmonary disease. The diagnosis is usually made by a combination of clinical, pathologic, and serologic tests, led by the patient’s review of systems.
Treatment for SSc is based on the underlying organ of involvement. A recent meta-analysis created recommendations by organ system.4 The drug of choice for interstitial lung disease is usually cyclophosphamide (Cytoxan), despite its toxicity. This patient was referred to the pulmonary team for further management. Due to the risk of infertility and the mild status of her lung disease, she opted not to take this medication.
Although few studies specifically address the treatment of depigmentation in SSc the treatments chosen are the same as those for vitiligo. Options include topical or systemic steroids, topical calcineurin inhibitors, vitamin D3 analogs, phototherapy, laser therapy and photochemotherapy.5 Success rates vary widely based on patient demographics and the location and extent of disease. The best responses to therapy are seen in younger patients; those with recent onset of disease; those with darker skin types; and for lesions on the face, neck and trunk.
Topical fluocinonide resulted in 50% repigmentation of the area on this patient’s chest. Her nailfolds showed no response. Laser treatment was too costly for the patient to pursue this option.
Emily Grauel is a third-year medical student at Virginia Commonwealth University School of Medicine in Richmond. Julia R. Nunley, MD, is professor of dermatology at Medical College of Virginia Hospitals, also in Richmond.
1. Gabrielli A, Avvedimento EV, Krieg T. “Scleroderma.” N Engl J Med. 2009;360:1989-2003.
2. Chifflot H, Fautrel B, Sordet C et al. “Incidence and prevalence of systemic sclerosis: a systematic literature review.” Semin Arthritis Rheum. 2008;37:223-235.
3. De Villiers WJ, Jordaan HF, Bates W. “Systemic sclerosis sine scleroderma presenting with vitiligo-like depigmentation and interstitial pulmonary fibrosis.” Clin Exp Dermatol. 1992;17:127-131.
4. Kowal-Bielecka O, Landewé R, Avouac J et al. “EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR).” Ann Rheum Dis. 2009;68:620-628.
5. Felsten LM, Alikhan A, Petronic-Rosic V. “Vitiligo: a comprehensive overview Part II: treatment options and approach to treatment.” J Am Acad Dermatol. 2011;65:493-514.