Malignant Atrophic Papulosis

Updated: Apr 10, 2019
Author: L Campbell Levy, MD; Chief Editor: BS Anand, MD 

Overview

Background

Kohlmeier described a case of malignant atrophic papulosis (MAP) as a form of thromboangiitis obliterans in 1941.[1] It was recognized as a distinct clinical entity by Degos in 1942, hence the name.[2] Since that time, two distinct clinical patterns have been recognized. A malignant variant affects multiple organ systems and results in death (most commonly from intestinal perforation) within a 2-year period. A benign form that is limited to the skin has a prolonged survival and low morbidity. A rare familial form has been described, which also has a benign prognosis.

Pathophysiology

Malignant atrophic papulosis is a multisystem disorder involving small-caliber blood vessels. The disease is characterized by narrowing and occlusion of the vascular lumen by intimal proliferation and thrombosis, which leads to ischemia and infarction of the involved organ systems. Malignant atrophic papulosis is different from other vasculitides in that inflammation is not a prominent component of the disease. Malignant atrophic papulosis may involve the gastrointestinal and genitourinary tracts, central and peripheral nervous systems, skin, heart, lungs, eyes, pancreas, adrenals, and kidneys. The disease involves the skin alone in 37% of cases. The gastrointestinal tract is involved in about 50% of cases, and neurologic involvement occurs in approximately 20% of patients.[3]

Etiology

The etiology of malignant atrophic papulosis is unknown.[4] Autoimmune, hypersensitivity, viral, and genetic factors leading to endothelial dysfunction, small vessel vasculitis, or a coagulopathy have all been implicated. None has been confirmed or is supported by strong evidence. It has also been theorized that malignant atrophic papulosis may not be a distinct disease but rather several processes that converge to produce characteristic clinical and histologic findings.

Epidemiology

International data

Malignant atrophic papulosis is a rare disease, with approximately 200 cases reported to date.[5] This makes early diagnosis challenging.[6]

Most of the cases are sporadic, although a benign familial variant has been described. There have been approximately 30 reports involving 10 families. Only 4 of the 30 cases (13%) had systemic involvement.

Race-, sex-, and age-related demographics

Most cases of malignant atrophic papulosis reported from Europe and North America have been in white individuals. The disease has also been reported from Japan, India, and Africa.

Malignant atrophic papulosis affects both sexes. A slight male predominance has been reported but has not been substantiated.

The disease predominantly affects young adults, but cases have been described in infants and children.[7, 8, 5] Moss et al reported the case of a 6-month-old infant who was admitted to the emergency department with bilateral subdural fluid collections and skin ulcers that resembled cigarette burns.[7] Due to the infant's presentation, child abuse was suspected; however, during the child's admission, his neurologic condition continued to deteriorate, with progressive cerebral infarctions, and his skin ulcers revealed failure to heal. Histology confirmed the diagnosis of Degos disease. The child received palliative care and died 8 weeks after presentation.[7]

Prognosis

Patients with multisystem involvement have a poor prognosis, with a mean survival of approximately 2 years. Patients with the benign, cutaneous-limited variant have a much better outcome with a prolonged survival.

Mortality/morbidity

The morbidity and mortality of malignant atrophic papulosis depend upon the extent of disease involvement. The benign cutaneous variant occurs in approximately 4%-15% of cases. Most patients with the cutaneous-limited variant, who were monitored for over a decade, have not suffered significant morbidity. With systemic disease, the reported mean survival is approximately 2 years, but there is a wide variation, from less than 1 year to more than 12 years.

The main causes of morbidity and mortality are bowel infarction, bowel perforation, CNS infarction and hemorrhage, and pleuropericardial disease.[9, 10] The benign and malignant variants are clinically indistinguishable initially but become distinct once systemic complications arise. Lack of systemic involvement at 2 years after diagnosis portends a better prognosis.

Complications

Complications of malignant atrophic papulosis include the following:

  • Gastrointestinal bleeding

  • Intestinal perforation and peritonitis

  • Bowel ischemia

  • Cerebral infarcts

  • Spinal cord infarcts

  • Subdural/intracerebral hemorrhage

  • Neuropathy

  • Pericarditis

  • Pleuritis

 

Presentation

History

Most patients have cutaneous involvement, and it is these manifestations that prompt patients to seek clinical evaluation. Patients usually describe multiple small papular skin lesions. Typically, the lesions involve primarily the trunk and limbs; they are rarely painful, tender, or pruritic. The lesions appear in crops with a new group of lesions developing intermittently. Palms, soles, face, scalp, and genitalia tend to be spared, but exceptions have been noted. Specifically, multiple cases of painful genital ulceration have been reported.

Gastrointestinal manifestations most often appear several weeks, months, or even years after a cutaneous eruption, although there are infrequent reports of gastrointestinal symptoms preceding the skin lesions. The gastrointestinal manifestations are most often nonspecific and include abdominal pain, abdominal distention, nausea, vomiting, diarrhea, or constipation. Patients with extensive involvement of the gastrointestinal tract also may experience weakness, fatigue, weight loss, or symptoms of malabsorption. In late stages of malignant atrophic papulosis, gastrointestinal hemorrhage, bowel infarction, fistulae, and perforation may be observed.

Neurologic involvement is also common. As with the gastrointestinal symptoms, neurologic symptoms are usually nonspecific. Involvement of both central and peripheral nervous systems can occur and can cause paresthesias of the face and extremities, headaches, dizziness, seizures, hemiplegia, aphasia, paraplegia, and gaze palsy.

Symptoms from involvement of other organ systems are rare. Chest pain and dyspnea may occur with involvement of the lungs, pleura, pericardium, and myocardium. Involvement of the eyes can result in diplopia, blurred vision, and visual field defects.

Physical Examination

The recognition of the skin lesions is critical to an accurate diagnosis. The early lesions are pinkish papules that appear in bouts, are about 2-5 mm in size, and occur on the trunk and extremities while usually sparing the face, palms, soles, and scalp. Within a few days, these papules become umbilicated, with depressed centers. At presentation, most of the papules have reached the atrophic stage and appear as porcelain-white lesions covered with a fine scale and surrounded by a 1- to 2-mm erythematous border. Individual lesions usually remain stable, without a tendency to spread or coalesce with neighboring lesions. However, a spectrum of presentations has been posited, including the evolution of red, painful, subcutaneous red nodules to the typical atrophic papule.

Lesions comparable to those on the skin occasionally may be observed on the conjunctiva or on the genital and buccal mucosa. Lesions have also been observed on the vocal cords.

Patients with widespread systemic disease may exhibit signs of neurologic involvement such as hemiparesis, cranial nerve abnormalities, and paresthesias. Ocular abnormalities (eg, ptosis, optic neuritis, subcapsular cataracts) may occur; papilledema also may be found.

 

DDx

Diagnostic Considerations

Diagnostic considerations include the following:

  • Thromboangiitis obliterans

  • Antiphospholipid antibody syndrome

  • Lymphomatoid papulosis

  • Arthropod bite

  • Atrophie blanche

  • Tumid lupus

Differential Diagnoses

Workup
 

Workup

Laboratory Studies

There are no laboratory results that are pathognomonic of malignant atrophic papulosis. Complete blood cell (CBC) count, serum chemistries, erythrocyte sedimentation rate (ESR), and C-reactive protein findings are usually within the reference ranges. Results of serum immunoglobulins, complement assays, antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and other serologies are usually unremarkable as well. Coagulation studies are generally normal. However, protein S deficiency, antiphospholipid antibodies, and altered platelet function have been identified in isolated cases of malignant atrophic papulosis, resulting in abnormalities of various coagulation parameters.

Imaging Studies

In patients with neurologic involvement, computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain may show ischemic infarcts, intracerebral bleeding, subdural hemorrhage, cord infarcts, and diffuse homogeneous dural enhancement. A cerebral angiogram may reveal narrowing and occlusion of the small intracranial arteries. Generalized nonspecific slowing on EEG and axonal and demyelinating polyneuropathy on electromyogram (EMG) also have been found in selected patients.

In patients with abdominal discomfort and cutaneous malignant atrophic papulosis, plain radiographs, CT scan of the abdomen, or small bowel follow through may show intra-abdominal perforation, abscesses, or fistulae indicating systemic involvement.

Other Tests

Gastrointestinal involvement may be observed on endoscopy, even in asymptomatic patients. Lesions similar to those on the skin are most often observed in the small bowel but can also be seen in the stomach, esophagus, duodenum, colon, and rectum.

Laparoscopy may show typical lesions consisting of white spots with hyperemic borders on the serosal surface of the bowel and the peritoneum.

Malignant atrophic papulosis infrequently causes symptomatic involvement of other organs (eg, lungs, heart), which may require appropriate tests such as chest x-ray, electrocardiography (ECG), and echocardiogram.

Procedures

Skin biopsy usually is required for histologic diagnosis.

Histologic Findings

Biopsy samples of early lesions have shown nonspecific findings, including some perivascular and perineural inflammatory infiltrates. However, a typical mature lesion of the skin usually shows an atrophic hyperkeratotic epidermis overlying an inverted, cone-shaped area of necrosis in the dermis. The small-caliber blood vessels in the dermis show narrowing of the lumen by endothelial proliferation and, sometimes, partial or complete occlusion of the lumen by a thrombus.

Although lesions may show lymphocytic perivascular infiltrates, it is the relative paucity or complete absence of inflammatory cells at the periphery of affected vessels that distinguishes malignant atrophic papulosis from other vasculitides. Similar changes are observed in the small arteries and arterioles on histologic examination of other affected organs. Although prominent IgA deposits have been reported in isolated cases, direct immunofluorescence has yielded variable results.[11]

A relatively recent in vivo skin imaging technique may provide more detailed histologic findings in malignant atrophic papulosis. Reflectance confocal microscopy (RCM) appears to have not only image resolutions similar to that of conventional microscopy (about 1 μm) but also a depth of up to 200 μm and a close correlation between RCM findings and underlying histologic changes.[12]

 

Treatment

Approach Considerations

In severe cases, the patient may need to be admitted for a diagnostic evaluation to determine the extent of disease and to exclude other vasculitides such as systemic lupus erythematosus (SLE) or polyarteritis nodosa (PAN). Malignant atrophic papulosis should be considered in patients diagnosed with a nonspecific vasculitis that does not respond to immunosuppressive therapy.

Admit the patient to the hospital immediately if a complication such as gastrointestinal bleeding, perforation, or stroke is suspected. Transfer may be required for surgical intervention in those patients who develop peritonitis or intracranial bleeding. (Surgical treatment usually is required for patients who develop complications such as gastrointestinal bleeding, intestinal perforation, bowel infarction, or intracranial bleeding.)

Broad-spectrum antibiotics may be used in patients with intestinal perforation in the perioperative period. Discontinuation of prothrombotic medications (eg, oral contraceptives) should be considered.

Monitor patients with isolated cutaneous disease for the development of systemic disease.

Medical Care

Because most patients initially present with skin manifestations, they typically are seen by a dermatologist, at which time a diagnosis usually is made. The skin lesions are not painful, usually do not itch, and generally do not require treatment. Patients who have gastrointestinal or neurologic symptoms should undergo an appropriate workup to detect systemic disease, which is an important determinant of prognosis.

Many medications have been tried for treatment of malignant atrophic papulosis, without consistent success.[13] Degos suggested that anticoagulants might be effective, but others have shown them to be of no benefit. Isolated cases of benign cutaneous disease have responded to nicotine patches (5 mg/d transdermal patch) and pentoxifylline plus aspirin. Similarly, antiplatelet drugs, such as aspirin and dipyridamole, may reduce the number of new papules but have not shown any consistent benefit in systemic disease. Other drugs (eg, corticosteroids, immunosuppressants, sulfonamide, tetracycline, penicillin, interferon 2 alpha) have been shown to be ineffective in altering the course of the disease.

No special dietary or activity considerations are necessary.

Consider consultations with the following specialists:

  • Dermatologists

  • Gastroenterologists

  • Neurologists

  • General surgeons

  • Neurosurgeons

  • Rheumatologists

  • Ophthalmologists

 

Medication

Medication Summary

To date, no medications have proven beneficial in the treatment of malignant atrophic papulosis.