Degos Disease

Updated: Feb 07, 2017
  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

In 1941, in an article entitled "Multiple Hautrekrosen bei Thromboangiitis obliterans," Kohlmeier described a case of a disease that has now been termed malignant atrophic papulosis (MAP) or Degos disease (DD). Degos recognized it as a distinct clinical entity in 1942.

Research suggests that Degos disease is a genetic disease of complement or some other clotting factor or system. [1] This is supported by the fact that eculizumab, a C5 blocker, can effectively treat systemic Degos disease.

Broadly speaking, Degos disease is a vasculopathy or an endovasculitis. It is an occlusive arteriopathy involving small-caliber vessels. Specifically, it is a progressive, small- and medium-size arterial occluding disease, leading to tissue infarction and initially involving the skin. Degos disease occurs both in a limited benign, cutaneous form and in a potentially lethal multiorgan, systemic variant. [2]

In the skin, Degos disease initially manifests with erythematous, pink or red papules. These papules heal to leave scars with pathognomonic, central, porcelain white atrophic centers. These papules usually have a peripheral telangiectatic rim.

In the systemic variant of Degos disease, the gastrointestinal tract is affected in 50% of cases. Intestinal perforation is the most severe complication and the most common cause of death in systemic Degos disease. [3] Other systems can also be involved; approximately 20% of cases of systemic Degos disease involve the CNS. Systemic manifestations usually develop from weeks to years after the onset of skin lesions, or, in rare instances, they may precede the skin lesions.

Because of the broad overlap in clinical and histological findings, High et al [4] contended in 2004 that Degos disease may not be a specific entity but, rather, may represent a common end point to a variety of vascular insults, many of which have not been fully elucidated. In 2003, Ball et al [5] proposed that Degos disease is just a variant of lupus.

Unlike lupus, (1) Degos disease does not involve the face, (2) it does not respond to therapies such as corticosteroids that at least abate lupus, (3) it does not manifest with photosensitivity, (4) viral inclusions are present in some cells in patients with Degos disease, and (5) systemic Degos disease is universally fatal, usually within 1-2 years, whereas lupus (even if severe) takes years to be fatal. [6]

Wilson et al [7] reiterated that malignant atrophic papulosis/Degos disease has both a (1) limited, cutaneous type and a (2) systemic, fatal variant.

Guhl has noted a case of Wegener granulomatosis that manifested with multiple whitish papules, perhaps similar to those in Degos disease. [8]

New cases of Degos disease continue to be described, with no fully effective cure yet devised. [9, 10]

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Pathophysiology

The etiology and the pathophysiology of Degos disease are unknown. Some have classified Degos disease as a vasculitis, a mucinosis, or a thrombotic disorder. In most cases, no circulating immune complexes, antiendothelial cell antibodies, or anticardiolipin antibodies are isolated. Although, in some cases, antiphospholipid antibodies of uncertain significance are identified. A source of confusion exists in understanding atrophic papulosis. It is likely that the differences in blood vessels in each area of the body (eg, skin, brain, intestines) help explain the different phenotypes of disease.

Some authorities suggest that Degos disease involves a primary endothelial cell defect with secondary thrombosis, leading to infarctive changes. No evidence exists supporting specific antibody-mediated damage. Additionally, medications and toxic chemicals do not appear to induce Degos disease.

The actual physical damage to blood vessels involves, at least in part, impaired fibrinolytic activity and alterations in platelet function. Classifying Degos disease as a vasculitis may not be appropriate because inflammation of the vessel walls is minimal and because immune complexes have not been found in the vessel walls.

Three possible mechanisms for this pathology have been suggested: disturbance in immunity, viral infection, and abnormality in the clotting system of blood.

In familial cases, an autosomal dominant mode of inheritance has been suggested, but this is uncertain.

In molecular analysis of cases of Degos disease with only cutaneous lesions, no paramyxovirus was identified by polymerase chain reaction.

The effectiveness of eculizumab at treating Degos disease must transform our understanding of the disease. As eculizumab is a hematological drug that blocks complement component 5 (C5), Degos disease may, in fact, be a hematological/endothelial/clotting disease that involves C5 in some pathological cascade. Degos disease thus is not a disease of immunity and should not be considered as a vasculitis. A genetic defect that parallels that of paroxysmal nocturnal hemoglobinuria (PNH) would not be surprising. Scheinfeld has discussed this concept at length. [11]

Support for the idea that Degos disease is an genetic defect of the endothelial tissue (with or with out a viral trigger) comes from Passarini who noted that in a patient suffering from systemic Degos disease who received an organ transplant, who died, on autopsy did not have any Degos disease–like changes in the transplanted tissue. [12]

A report from Japan published in 2013 investigated the expression of stromal cell–derived factor (SDF)-1/CXCL12 in Degos disease. Bone marrow stromal and endothelial cells secrete SDF-1/CXCL12. SDF-1/CXCL12 activates megakaryocyte precursors. SDF-1/CXCL12 co-stimulates platelet activation. The study compared 2 patients with Degos disease, 1 patient with cryoglobulinemia, 1 patient with antiphospholipid syndrome, and 2 healthy controls. No staining was noted in the antiphospholipid syndrome, cryoglobulinemia, or control subjects. In the Degos disease patients, investigators saw intense SDF-1/CXCL12 staining infiltrating inflammatory cells. These cells were located in the perivascular, intravascular, and perineural tissue. This finding supports the theory that Degos disease is perhaps, in part, an endothelial disease. [13]

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Epidemiology

Frequency

Degos disease is rare. About 200 cases have been reported in the world literature.

Race

Some state that Degos disease generally occurs in white young adults. However, Degos disease is reported in blacks in Africa, Arabs in Jordan, [14] Asians in Japan, and elsewhere. Any racial link is uncertain.

Sex

In 1997, Katz et al [15] noted that the disorder usually occurs in young adults, and the male-to-female ratio is approximately 3:1.

Wilson et al [7] reviewed benign cutaneous malignant atrophic papulosis in 34 men and women (30 adults and 4 kids) and noted that benign malignant atrophic papulosis is more commonly reported in women, at a female-to-male ratio of 3:1.

Age

All ages are affected. The fatal systemic variant of Degos disease can occur in children. In 1999, Lankisch et al [16] described a 16-year-old white adolescent girl with acute abdominal pain due to visceral involvement of Degos disease that required extensive small-bowel resection. The skin manifestations had been present for 2 years before the correct diagnosis was made. She died as a result of CNS involvement from Degos disease.

Jalil et al [17] described a case in a 2-year-old child who presented with chronic abdominal pain of uncertain origin.

The benign cutaneous variant of Degos disease can occur in adults. Wilson et al [7] looked at 34 patients with benign cutaneous malignant atrophic papulosis and found their average age was 37.6 years. In 1998, Farrell et al [18] described a case of a 44-year-old woman with Degos disease and a lupus anticoagulant who, 4 years later, was alive and without systemic involvement. Electron microscopy of the white papules demonstrated interwoven tubular structures within the endothelial cells. This was consonant with reports in previous studies of Degos disease. Farrell et al [18] thought that aspirin (300 mg/d) kept her cutaneous Degos disease in check. In 1998, Requena et al [19] described a 58-year-old homosexual man with AIDS who developed typical cutaneous lesions of malignant atrophic papulosis, with no visceral involvement detected 2 years after the diagnosis of Degos disease.

Degos disease can occur in infants. Degos disease has been reported in a 7-month-old girl who showed spontaneous aggregation of platelets. A good clinical response in this patient was obtained by treatment with aspirin and dipyridamole. [20]

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Prognosis

Patients with only skin lesions may have a good prognosis. Gastrointestinal involvement may occur in as many as 60% of patients, and death in such cases is likely. About 15% of patients with Degos disease have long-term survival, with disease often limited to the skin and with no manifestations of fatal bowel or CNS involvement.

Systemic Degos disease is frequently fatal within 2-3 years from the onset of systemic involvement. The cause of death is usually intestinal perforation. However, the range of survival time from time of diagnosis varies from less than 1 year to more than 12 years. Other causes of death include bowel infarction, pleuropericardial pathology, [21] and neurologic infarction and hemorrhage.

Wilson et al [7] reviewed the 24 reported instances of malignant atrophic papulosis malignant/systemic type and benign/purely cutaneous type in pediatric patients. They found that 14 cases (58%) were fatal. Patients died an average of 3.6 years after the diagnosis of malignant atrophic papulosis.

In  one patient, in whom skin and abdominal symptoms occurred at the same time, death from bowel hemorrhage followed in 6 months.

In 1996, Subbiah et al [22] described the neurologic features of a series of 15 patients with Degos disease at the Mayo Clinic. Each patient had the white papules that are the hallmark of Degos disease (biopsy proven). Long-term follow-up revealed 6 patients were dead. Nine patients with skin lesions only were nearly asymptomatic. Immunosuppressive and antiplatelet agents did not halt disease progression. CNS infarcts and hemorrhages with intravascular thrombi and without evidence of vasculitis were notable findings at autopsy.

Notash et al [23] reported a 48-year-old Iranian man with lethal systemic Degos disease.

Two reports describe acute abdomen associated with Degos disease, one fatal. [24, 25]

When associated with gastrointestinal tract or central nervous system involvement, patients with Degos disease have a poor prognosis and a high mortality.

In patients with benign cutaneous Degos disease, immunosuppression (in 1 patient with cyclosporine) can cause Degos disease to evolve into systemic fatal disease.

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Patient Education

Because systemic Degos disease is fatal, patients and their families should be educated in this regard.

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