Diagnosing Degos

Degos disease (malignant atrophic papulosis) is a rare progressive, small and medium size arterial occluding disease, leading to tissue infarction initially involving the skin and later the gastrointestinal, ocular and central nervous systems.

The disease is characterized by papules that develop porcelain-white centres and telangiectatic borders. This is the clue to the underlying disease which can affect the gastrointestinal tract and central nervous system and may lead to death.

The skin biopsy places the pathologist at the centre of the diagnostic evaluation. (See biopsy plates below and under Images

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.

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

In the skin, DD 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 DD, 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 DD. Other systems can also be involved; approximately 20% of cases of systemic DD 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.

Synonyms and related keywords

DD, malignant atrophic papulosis, papulosis atrophicans maligna, Kohlmeier-Degos-Delort-Tricot syndrome, Kohlmeier-Degos syndrome, Köhlmeier-Degos’ disease, Online Mendelian Inheritance in Man 602248, OMIM 602248, papuleuse maligne atrophiante, lethal cutaneous and gastrointestinal arteriolar thrombosis, fatal cutaneointestinal syndrome, thromboangiitis cutaneointestinalis disseminata, dermatite papulosquameuse atrophiante, MAP

Pathophysiology

The etiology and the pathophysiology of DD are unknown. Some have classified DD 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.

Some authorities suggest that DD involves a primary endothelial cell defect with secondary thrombosis, leading to infarctive changes. No evidence exists for antibodies to components of endothelial cells. Medications and toxic chemicals do not appear to induce DD.

The actual physical damage to blood vessels involves, at least in part, impaired fibrinolytic activity and alterations in platelet function. Classifying DD 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 DD with only cutaneous lesions , no paramyxovirus was identified by polymerase chain reaction (PCR).

Lab Studies

  • No specific laboratory test can be used to aid in diagnosing DD. In fact, most laboratory test results are normal, with the exception of the manifestation of anemia secondary to intestinal bleeding.
  • In 1 patient, laboratory examinations disclosed persistent elevations of the thrombin-antithrombin III (TAT) complex, plasmin-alpha 2 plasmin inhibitor complex (PIC), and cytotoxic T-cell subset (CD8 + CD11 – ), illustrating the coagulative, fibrinolytic, and immunologic implications of DD.
  • In a series of 3 patients with DD, prolonged euglobulin lysis time, increased plasminogen activator (PA) levels, and increased plasminogen activator inhibitor (PAI) activities were detected before and after a venous occlusion test, indicating an inhibition of fibrinolysis.
  • In a series of 3 patients with DD, electron microscopy demonstrated an increased number of Weibel-Palade bodies and a raised staining of von Willebrand factor in endothelial cells in 1 patient.
  • In a series of 3 patients, test results for coagulation and circulating anticoagulant were in the reference range.
  • In a series of 3 patients, the results of platelet adhesion showed decreased adhesion in 1 patient and increased adhesion in another patient. Platelet aggregation study results were in the reference range in 2 patients, and the results showed hyperactive spontaneous and induced aggregation in 1 patient.
  • Amounts of protein in the cerebrospinal fluid (CSF) and amounts of platelet aggregation have been reported as sharply increased in progressive stages of the disease. For example, laboratory results showed a gradual increase of CSF proteins (from 156 mg/dL to 602 mg/dL) and an extremely increased amount of platelet aggregation.
  • In DD, viruslike inclusions are frequently present in the endothelial cells and fibroblasts. C3 deposits and the presence of intracytoplasmic cylinders are also frequently present in the histiocytes.

Imaging Studies

  • MRI of the brain can show multiple cerebral infarctions accompanied by small hemorrhagic areas and gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement of the dura. They can also reveal intracerebral bleeding, subdural hemorrhage, and cord infarcts.
  • A cerebral angiogram may reveal narrowing and occlusion of small intracranial arteries. Specifically, a cerebral angiogram can depict stenosis, ectasia, and aneurysms involving the peripheral branch of arteries.
    EEG tests have shown generalized nonspecific slowing.
  • In some patients, electromyograms (EMGs) demonstrate axonal and demyelinating polyneuropathy.
  • With angiograms, stenoses can be observed in the celiac artery and the small arteries in the kidney.
  • In some patients, chest radiographs have depicted extensive calcification of the pericardium. Although pleural involvement and pericardial involvement have been reported in DD, constrictive pericarditis is most unusual, and radiographically demonstrable calcification of the pericardium has not been previously reported.

Other Tests

  • Endoscopy of the gastrointestinal tract (ie, stomach, esophagus, duodenum, colon, rectum) can show infarcted lesions or ulcers.
  • Laparoscopy of the intestine can show similar type lesions that manifest with white plaques with red borders on the serosal surface of the bowel and the peritoneum.

Histologic Findings

Early papules in DD are skin colored and can demonstrate a superficial and deep perivascular, periadnexal, and perineural chronic inflammatory cell infiltrate associated with interstitial mucin deposition. The overlying epidermis can show a mild vacuolar interface reaction, and, at this early stage, the histologic appearances can resemble tumid lupus erythematosus.

Fully developed papules can be raised with umbilicated porcelain white centers and a surrounding erythematous rim. Usually, wedge-shaped degeneration of collagen is present. A prominent interface reaction with squamatization of the dermoepidermal junction, melanin incontinence, epidermal atrophy, and a developing zone of papillary dermal sclerosis that resembles the early stages of lichen sclerosus et atrophicus in miniature can also be observed at histologic examination. These interface reactions are usually confined to the central portion of a punch biopsy specimen, corresponding to the central, porcelain white area seen clinically.

Histopathologic examination of the skin biopsy specimen can also show hyperkeratosis, epidermal atrophy, dermoepidermal separation, edema, and necrosis in the papillary dermis. Fibrinoid necrosis and thrombosis can be seen in the papillary dermis and in the vessels below the lesions. Others have noted that skin biopsy specimens show hyperkeratosis, atrophy of the epidermis, and necrobiosis of the collagen layer. Well-developed lesions with epidermal atrophy and hyperkeratosis overlying a wedge-shaped area of cutaneous ischemia extending into the deep dermis have also been observed. Superficial and deep perivascular lymphocytic infiltrate can be present at the edge of ischemic areas. Marked endothelial swelling and occasional platelet-fibrin thrombi can be present. The epidermis may show infarctive changes or scattered necrotic keratinocytes. Abundant acid mucopolysaccharides can be present in the dermis giving the appearance of a dermal mucinosis.

Direct immunofluorescence (DIF) yields conflicting findings with perivascular fibrin and complement in variable instances. An autopsy examination confirmed the clinical diagnosis of the syndrome by the finding of thromboangiitis of the Burger type, with bland infarcts of the small intestine and perforation of the jejunum. Microaneurysms of the bulbar conjunctival vessels have been described. Changes in the kidney manifest with thickening of the afferent glomerular arterioles and the capillary basement membrane.

Biopsy Plates

The lesion commonly has a wedge shape.The lesion commonly has a wedge shape. The epidermis is atrophic or even ulcerated.The epidermis is atrophic or even ulcerated. There is a mild dermal perivascular lymphocytic infiltrate.There is a mild dermal perivascular lymphocytic infiltrate. The vessels can appear swollen.The vessels can appear swollen. Sometimes intravascular fibrin thrombi can be seen.Sometimes intravascular fibrin thrombi can be seen.

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Last updated 24th March 2011. Originally added 26th July 2010.
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