Malignant form of atrophic papulosis with lethal abdominal involvement

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Atrophic papulosis (Köhlmeier–Degos disease or Degos disease) is a rare occlusive arteriopathy involving small-calibre vessels of the dermis, gastrointestinal tract, central nervous system (CNS) and occasionally other organs.[1, 2] It would appear to be a vasculopathy or an endovasculitis, with a purely cutaneous benign variant and a systemic variant with cutaneous manifestations (malignant atrophic papulosis). Gastrointestinal involvement is the most frequent and lethal systemic complication.[3] This is the most common cause of death, followed, less frequently, by CNS bleeding, and pleural or pericardial involvement.[4]

A 47-year-old woman was admitted to our Department because of a pruritic erythematous rash on the face, upper chest and arms. We noted over 100 erythematous dome-shaped papules of 5 10 mm in diameter that progressively developed central porcelain-like atrophic scars (Fig. 1c) surrounded by a telangiectatic rim involving the face, trunk, arms, lower limbs (Fig. 1a). The complete blood count, serum biochemistry analysis, kidney, liver and thyroid function tests and the erythrocyte sedimentation rate were all normal. ANA, ANCA, ENA, nDNA were all negative. Histopathological examination showed a widespread area of fibrosis in the dermis subjacent to an atrophic epidermis without mucin deposition (Fig. 2a,b). The vessel walls showed marked degeneration of fibro-hyaline tissue with significant reduction of the lumen (Fig. 2c). Treatment was started with methylprednisolone 16 mg/day together with hydroxychloroquine 200 mg/day, and a partial improvement was obtained. One month after corticosteroid therapy had commenced, the patient reported abdominal pain. Abdominal CT was performed in emergency (Fig. 1b). Unenhanced and contrast-enhanced CT scans during arterial and portal venous phase were performed in a patient suspected of mesenteric infarction. However, CT scan did not detect filling defects in the splanchnic circulation. CT images revealed a thickened ileal loop surrounded by mesenteric fat stranding indicative of localized inflammatory disease. Moreover, a minute amount of extraluminal gas was also observed next to the thickened ileal segment, highly suggestive of intestinal perforation. Explorative laparotomy revealed multiple ischemic changes throughout the entirety of the small bowel. The perforated bowel segment was resected and a side-to-side anastomosis of the small bowel was performed (Fig. 1d). Microscopic examination of the small bowel revealed involvement of small arteries with multifocal thrombi, severe fibrotic thickening of the vessel walls and partial lumen occlusion which impeded erythrocyte crossing (Fig. 2d). Corticosteroid treatment was suspended, and 100 mg ASA daily and intravenous pentoxifylline 1200 mg daily were added to the hydroxychloroquine. Despite this therapy, in the following months, the patient presented more typical cutaneous lesions on the trunk, limbs, neck, palms and soles. Five months later, the gastrointestinal progression of the disease led to the patient's death due to a severe acute secondary peritonitis.

Figure 1.

(a) The pathognomonic papules on the abdomen. (b) Axial arterial phase CT view shows mural thickening of an ileal segment (arrow) with peri-intestinal mesenteric fat stranding (star). An adjacent extraluminal gas bubble (arrowhead) is visible suggesting ileal perforation. (c) Scattered atrophic papules, with a porcelain-like appearance and erythematosus telangiectatic border. (d) Perforation of abscess on the side of the small bowel from microperforation of the mesentery.

Figure 2.

(a) Cutaneous tissue with severe fibrosis and diffuse atrophy of the epidermis of the skin subepidermal area, adnexal subtotal atrophy (haematoxylin and eosin, 2.5 x). (b) Extreme atrophy of the epidermis and dermis (Azan-Mallory,10 x). (c) Severe epidermal atrophy, dense fibrosis of subepidermal vessel wall, partial occlusion of lumen due to fibro-hyaline substance (Azan-Mallory, 20 x). (d) Histological section of the ileal wall, with vasculopathic pattern. (Azan-Mallory, 40 x).

Approximately 200 cases of atrophic papulosis have been reported in the literature, including both the benign cutaneous form and the potentially lethal systemic variant. To date, there is no reliable way of distinguishing these two variants and systemic involvement may develop years after the onset of skin lesions. For this reason, in the presence of the typical pathognomonic lesions of atrophic papulosis, it is crucial to exercise caution before diagnosing the benign variant and perform regular medical follow-up of the patients. The first manifestation usually occurs on the skin in the third and fourth decades of life in male patients although the benign form is more commonly reported in women.[4] No effective medical therapy for atrophic papulosis was known. Efforts with compounds that facilitate blood perfusion (acetylsalicylic acid, pentoxifylline, dipyridamole, ticlopidine and heparin) can be used as a first therapeutic approach. Fibrinolytic and immunosuppressive (cyclosporine-A, azathioprine, cyclophosphamide and corticosteroid) have been mostly unsuccessful.[5] More recently eculizumab and treprostinil have been employed. The effect of eculizumab on the skin and intestinal lesion are immediate and dramatic but it could not prevent the development or progression of systemic manifestations. Subcutaneous treprostinil has been reported to result in clearing of gastrointestinal and CNS findings in a single case with eculizumab-resistant disease.[6] Further studies will be needed to understand the mechanisms underlying the clinical expression and progression of atrophic papulosis and to define an effective and uniform therapy.

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