Chapter 171. Malignant Atrophic Papulosis (Degos Disease)

In the early 1940s, Köhlmeier first described malignant atrophic papulosis, whereas Degos, Delort, and Tricot recognized it as a specific entity a year later.1–3 We now know that the clinically distinctive lesion of the so-called Degos disease is a marker of a cutaneous thrombo-obliterative vasculopathy rather than of a specific disease per se. Indeed, such lesions can be found in at least two distinctive clinical settings: (1) as an apparent idiopathic disease, either classic Degos disease or its benign variant, or (2) as a surrogate clinical finding in some connective tissue diseases such as the antiphospholipid syndrome, lupus erythematosus, dermatomyositis, and systemic sclerosis.

Classic Degos disease is rare, with about 200 reported cases. It almost always occurs in Caucasians, but cases have been observed in African-American patients and in Japan. The disease most commonly presents between the third and fourth decades, but can occur at any age. Men are more often affected than women (ratio, 3:1). The majority of cases are sporadic, but familial cases have been described, and most of these cases are consistent with an autosomal dominant pattern of inheritance.4

The etiology of Degos disease is unknown. The histopathologic findings in patients with malignant atrophic papulosis suggest a primary vaso-occlusive process. Thus, a vascular coagulopathy and/or endothelial cell damage should be considered as the major pathogenic mechanism. A combination of prothrombotic factors possibly plays a role in triggering the full-blown disease. Extensive studies of prothrombotic factors were performed in some patients with Degos disease, and no single abnormality was repeatedly identified. All patients should be screened for the presence of antiphospholipid antibodies/lupus anticoagulant and cryoglobulins, although Assier et al did not find the former in their series of 15 patients.5 Inhibition of fibrinolysis and platelet abnormalities, including increased platelet adhesiveness and spontaneous aggregation, were reported in some patients.5–8

The lesions of Degos disease should be viewed as a cutaneous marker indicative of intraluminal thrombosis. Several disease processes may converge to produce those clinical and histologic findings.

(Fig. 171-1)

History

Patients seek medical advice for the appearance of small cutaneous lesions that usually are neither pruritic nor painful. In some patients, history and/or review of systems will reveal signs indicative of extracutaneous involvement: abdominal pain, diarrhea, melena, nausea, blurred vision, hemiparesis, paresthesia, or any other sign indicative of an ischemic event. History can also give a clue to previous thromboembolic or obstetrical events suggestive of the antiphospholipid antibody syndrome.

Cutaneous Lesions

Cutaneous lesions start as crops of 2–10 mm, largely asymptomatic or mildly pruritic, fleshy or rose-colored macules that soon become round, smooth, often dome-shaped firm papules (Fig. 171-2). Some lesions display central umbilication and/or necrosis (Fig. 171-3). These lesions evolve over days or weeks to porcelain-white, atrophic papules with a rim of rosy erythema and/or telangiectases (Fig. 171-4). A fully developed lesion therefore closely resembles lesions of atrophie blanche. In time, the reddish border disappears, and only a varicelliform white scar remains. Usually, the lesions are separated from each other, but they may coalesce, leading to polycyclic atrophic areas or to skin ulcerations.

The lesions are localized on the trunk and limbs. Palms, soles, face, scalp, and genitalia are usually spared, although there are exceptions. Exclusive acral localization is suggestive of connective tissue disease. A linear distribution was reported.9 Eye involvement is possible, and the most common manifestation is an avascular patch on conjunctivae, but sclerae, episclera, retina, choroids, and optic nerves may be affected (see eFig. 171-4.1).

Classic Degos Disease

In classic Degos disease, the number of cutaneous lesions varies from a few to more than one hundred. Cutaneous findings usually precede the systemic manifestations that may involve the gastrointestinal tract, with bowel perforation and peritonitis, and/or the central nervous system, with hemorrhagic or ischemic stroke. Rarely, cutaneous lesions occur simultaneously or after gastrointestinal or central nervous system involvement. Postmortem studies have revealed small vessel thrombotic involvement of many organs, including kidney, bladder, prostate, liver, pleura, pericardium, lung, and eyes.10 Some patients with classic Degos disease have antiphospholipid antibodies, and this raises the possibility of a relationship with a primary antiphospholipid syndrome.

Benign Degos Disease

A benign form of Degos is now widely recognized. In this form, only skin involvement is found, and most of the familial cases are benign.4 Development during pregnancy has been reported in a patient with antiphospholipid antibodies,11 as well as a case occurring in a patient with acquired immunodeficiency syndrome.12 A patient developing Degos disease after interferon injections, a drug known to induce atrophie blanche-like lesions13 and microangiopathy,14 is known to the authors (L. Thomas, personal communication). There is no clear-cut distinction between the classic and the benign form of Degos disease, and there is no way by which one can predict which patients will or will not develop visceral involvement.

Degos Disease-Like Lesions or Secondary Degos Disease

Degos disease-like lesions can occur in patients with known lupus erythematosus, especially those with antiphospholipid antibodies, dermatomyositis, systemic sclerosis, granulomatosis with polyangiitis (Wegener's), Crohn's disease and during parvovirus B19 viremia, a virus with a known affinity for endothelial cells.15,16–18

Histopathology

Clinically, fully developed lesions reveal a cell-poor, wedge-shaped area of slight-to-severe dermal necrosis with dermal edema and copious mucin deposition, extending from the papillar dermis to the deep part of the reticular dermis (Fig. 171-5). At the base of the lesion, occluded vessels with occasional thrombosis, thickened vessel walls, proliferating endothelial cells, and sparse perivascular lymphocytic infiltrate can be found (Fig. 171-6). Yet, a full-blown leukocytoclastic neutrophilic vasculitis is never found in patients with malignant atrophic papulosis. This entity should therefore not be classified as vasculitis. Numerous secondary, epidermal changes can be found: hyperkeratosis, interface dermatitis, scattered necrotic keratinocytes, and atrophy. An associated sclerosing panniculitis was reported in one patient.19 Results of direct immunofluorescence studies have been inconsistent. Electron microscopy occasionally revealed tubuloreticular aggregates within endothelial cells of uncertain significance.

Because some of those histopathologic findings, such as mucinous infiltration of the dermis, interface dermatitis, and perivascular lymphocytic dermal infiltrate, are shared by lupus erythematosus and dermatomyositis, Degos disease is considered by some authors as a possible variant of lupus erythematosus.20

Other Laboratory Tests and Special Tests

There is no diagnostic or prognostic marker of the disease. A search for antinuclear antibodies, lupus anticoagulant, and anticardiolipin antibodies should be performed in each patient. An extensive exploration of hemostasis will sometimes reveal abnormalities. When the disease starts with a sudden onset, a parvovirus B19 infection should be suspected and circulating viral DNA should be searched by PCR.18

Clinical evaluation can confirm secondary Degos disease if signs suggestive of connective tissue disease or antiphospholipid syndrome are present. If clinical evaluation reveals signs of intestinal or cerebral involvement (pain, diarrhea, hemiparesis, blurred vision, paresthesia), imaging studies including cerebral magnetic resonance imaging and/or endoscopic evaluation/laparoscopy are mandatory.

The diagnosis is usually established clinically, because of the distinctive skin lesion. A confirmatory biopsy should always be performed.

(Box 171-1)

Complications

Death related to an ischemic cerebral or gastrointestinal event is the major complication of Degos disease. Gastrointestinal hemorrhage, perforation, and peritonitis are the most frequent complications of the disease and are the major ominous events. Neurologic complications, including hemiparesis, aphasia, multiple cranial nerve involvement, monoplegia, sensory disturbances, and seizures, are less common. Rarely, progressive neurologic involvement can lead to death, especially in children. Exceptionally, death can result from respiratory failure or myocardial infarction.

Although absence of visceral involvement 2 years after diagnosis portends a better prognosis, systemic involvement can occur up to many years after initial cutaneous lesions and thus it is impossible to predict the outcome. Lethality is above 50% if patients present with extracutaneous involvement, and most of these patients die within 2–3 years mainly because of severe intestinal involvement. Familial Degos disease bears a better prognosis.4

Due to the rarity of Degos disease, there are no controlled clinical trials, but only anecdotal reports. Yet, in some aspects, Degos disease resembles livedoid vasculopathy, and, therefore, some treatments reported to be efficient in patients with the former entity are worth trying.

Secondary Degos disease occurring in patients with known connective tissue disease should involve, in our opinion, the introduction of antiplatelet agents in addition to the standard treatments otherwise required by those patients.

Patients with classic Degos disease should be screened for all known preventable cardiovascular risk factors. Patients should cease smoking, and their lipid levels should be screened and lowered, if necessary, using statins.

First-line treatment of patients with Degos disease should include platelet aggregation inhibitors (aspirin, clopidogrel, dipyridamole) (Box 171-2). A substantial number of patients responded to aspirin and dipyridamole.6,7,12 A number of anecdotal treatments, including antibiotics, chloroquine, immunosuppressive agents, phenylbutazone, and fibrinolytics, have been reported with variable success. Systemic steroids have been reported to exacerbate the disease and should not be prescribed.21 Heparin and other anticoagulation strategies such as antivitamin K (warfarin, fluindione) have variable success rates. Yet, by analogy to livedoid vasculopathy, low-molecular-weight heparin as well as the newer anticoagulants might warrant a trial in the acutely ill patient not responding to antiplatelet agents.22 Intravenous immunoglobulins should be considered in patients not responding to other treatments or in the acutely ill.18,23

The author thanks Jean-Hilaire Saurat for his work on this chapter in previous editions.