The Red Flag

Presentation 

The rash that caused a 43-year-old man to be referred to our clinic produced no discomfort, but it signalled a very rare and dangerous disease. Over the previous 6 months he had developed a progressive papular eruption on his trunk, extremities, and genitalia. It did not interfere with his daily activities, and he denied itching or burning. The lesions, about 5 mm in size, were initially dome-shaped red papules covered by normal epidermis (Figure). After a few days, the papules became umbilicated and encircled by an erythematous rim. The border disappeared after several weeks, and the lesions healed within a few months, leaving a small, porcelain-white, atrophic, varicelliform scar. Aside from nicotine abuse, the patient's past medical history was normal.

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Figure. The patient had these skin lesions on the lower leg. A, These disseminated, dome-shaped, red and white papules are in different stages of evolution. B, An erythematous rim surrounds the atrophic, porcelain-white center of a lesion. C, A hand-held dermoscope provides a magnified visualization of skin lesions (10x). D, Dermoscopy of a lesion shows multiple convoluted small vessels with no signs of hemorrhage around a glassy, avascular papule.

Assessment 

A complete general examination revealed no further pathology, other than mild eczema of the hand. Epiluminescence microscopy was performed using a handheld DermoGenius dermoscope (Biocam GmbH, Regensburg, Germany), which magnified the skin lesions 10-fold. Red spots and convoluted small-caliber vessels surrounded a hyaline, avascular, umbilicated papule. Hemorrhage was not evident. Histopathologic examination of a lesion from the trunk disclosed an inverted, wedge-shaped area of sclerosis in the underlying dermis with mucin deposition in the periphery. Focal perivascular lymphocyte infiltration with no indication of vascular thrombosis or overt necrosis was observed.

The patient's complete blood cell count, erythrocyte sedimentation rate, routine blood chemistries, and coagulation studies, including a fibrinogen assay, were normal. Moreover, immunoglobulin levels were within normal range, and tests for antinuclear antibody and antiphospholipid antibody were negative. Treponema pallidum hemagglutination testing also was negative. To exclude any systemic manifestations, we performed further investigations. Ophthalmologic examination was without any pathologic findings. Gastrointestinal involvement was excluded by a stool guaiac test and an endoscopy.

Diagnosis 

The disseminated papular lesions of different ages displayed an eye-catching, peculiar, dermatoscopic picture that, combined with the histological findings, led to the diagnosis of malignant atrophic papulosis or Degos' disease. These red papules undergo characteristic dynamic changes over time, exhibiting a porcelain-white, centrally-umbilicated center after several days and finally evolving into small, atrophic scars after some months. On histologic examination, inflammatory reactions marked by interface dermatitis or perivascular infiltrates; dermal necrosis; collagen degeneration; and mucin deposition can be found, depending on lesion stage. Intravascular platelet-fibrin thrombi might be present but are not mandatory. Direct immunofluorescence exhibits conflicting findings.1 Lymphomatoid papulosis, necrotizing vasculitis, atrophie blanche, guttate lichen sclerosus, guttate morphea, syphilitic rash, and scleroderma, all part of the differential diagnosis, were thus excluded.

Malignant atrophic papulosis is a rare, multisystem, small-vessel disease of uncertain etiology, with fewer than 200 cases reported so far. Disease onset can occur at any age but is rare in young children. Various pathogenic mechanisms, including abnormalities in the blood-clotting system, vasculitic and autoimmune processes, and primary defects of endothelial cells due to viral infections, have been suggested because all can lead to an occlusive, small-vessel vasculitis resulting in tissue ischemia.2, 3

Classically, besides the typical skin involvement, which is the usual cause for initial presentation, involvement of other organ systems is possible at any stage of the disease. Disseminated vasculitis can result in microinfarctions affecting several organs, and this has a poor prognosis: death in patients with systemic malignant atrophic papulosis usually occurs within 2-3 years of the onset of organ involvement.3 Ischemic infarcts of the gastrointestinal tract and their complications govern disease outcome; bowel perforation is the most common cause of death. The gastrointestinal tract—mainly the small intestine—is generally affected in 50-60% of all cases.4 Clinical symptoms are multiform and nonspecific and include dyspepsia, diarrhea, gastrointestinal bleeding, bowel fistula and acute abdominal pain.5, 6

The central nervous system is affected in about 20% of cases of systemic malignant atrophic papulosis.7 Patients might report memory loss, headaches, or seizures. The deadliest complication is cerebrovascular infarction. Moreover, involvement of the cardiopulmonary system can result in weakness, chest pain, and collapse, and ocular involvement might cause loss of vision or diplopia.8

However, some patients have been reported to survive for many years with only skin lesions. If confined to the skin, the disease has a benign course with a good prognosis and no significant morbidity or mortality.9 The only finding that might be associated with a better outcome—a rather benign course confined to the skin—is the histologic absence of thrombotic, occlusive vascular changes and a lack of dermal necrosis.10 Perhaps a purely cutaneous variant of malignant atrophic papulosis exists; this would present with disseminated red papules on the trunk, extremities, and genitalia but would not have additional fatal visceral involvement.

Normally, the papular rash precedes systemic symptoms. Therefore, the rather typical skin lesions represent a crucial red-flag sign, indicating possible fatal consequences. Dermoscopy is especially important in uncovering the impressive telangiectatic rim that differentiates atrophic papulosis from other papular skin lesions. The morphology or extent of the skin manifestations, however, cannot predict the patient's prognosis.

Management 

There is no standard treatment for malignant atrophic papulosis. In an attempt to correct presumed underlying causes, various drugs have been tried, including antiplatelet agents, such as aspirin and dipyridamole, heparin, fibrinolytics, thalidomide, anti-inflammatory agents, and corticosteroids.11

No effective therapy is available for systemic disease, and the outcome mostly remains fatal. In these cases, symptomatic, emergency, and palliative treatment of ischemic complications is demanded. However, for solely cutaneous forms of malignant atrophic papulosis, treatment with antiplatelet agents has shown some clinical effect in stabilizing or even reducing skin lesions; this would be the most promising therapeutic approach to date.12

After we excluded any systemic involvement, we began treating our patient with aspirin, 300 mg, daily. He is followed with regular clinical and diagnostic examinations, and at his 6- and 9-month visits, no signs of disease progression were evident.