Malignant atrophic papulosis (Degos disease) with central nervous system involvement.

A 49-year-old man presented with a 2-year history of weakness and sensory disturbances in the bilateral lower extremities, vesicorectal dysfunction, and progressive gait disturbances. Brain MRI revealed multiple ischemic and hemorrhagic cortical/subcortical lesions with patchy enhancement involving the frontal and parietal lobes, suggesting the possibility of distal perforating arteries injury. Spine MRI revealed lesions of the cervical and thoracic spinal cord with associated enhancement. The diagnosis of malignant atrophic papulosis (Degos disease) with central nervous system involvement was prompted by the characteristic skin lesions.

Atrophic Papulosis.

BACKGROUND: Atrophic papulosis (AP) is a rare obliterating vasculopathy characterized by specific skin lesions. The etiology and the pathophysiology of the disease remain unclear. The treatment is still empirical, while the malignant form of the disease is associated with a poor prognosis. SUMMARY: The underlying pathogenesis of AP includes three mechanisms with vasculopathy, coagulopathy, and endothelial dysfunction. Benign and malignant forms of AP are described. The benign form is confined to the skin. The pathognomonic skin lesions evolve over time and are large papules with an atrophic porcelain-white center and an erythematous rim. However, systemic involvement can occur months or years after the initial skin features. In this latter case, the associated mortality is very high with a mortality rate of over 65% in some series. Gastrointestinal involvement and central nervous system infarctions are the most frequent causes of death. Treatment is empirical with the use of antiplatelet therapy, anticoagulants, steroids, intravenous immunoglobulins, and immunosuppressive agents. Recent evidence shows that eculizumab, a complement inhibitor, is the most effective therapy in malignant AP with gastrointestinal involvement of the disease and should be combined with treprostinil to prevent relapse.

Degos disease in a child presenting with acute renal failure.

Degos disease, also termed malignant atrophic papulosis, is a rare systemic vaso-occlusive disorder, seldom reported in the pediatric population. The pathognomonic skin lesion in Degos disease is a papule with an atrophic porcelain-white center with an erythematous, telangiectatic rim. The benign form of the disease remains limited to the skin, whereas, in others, it progresses to thrombotic vasculopathy in multiple organs including the gastrointestinal, cardiorespiratory, and central nervous systems, with a high mortality rate. We present a rare case of Degos disease in an adolescent female, presenting as acute renal failure secondary to thrombotic vasculopathy, with the characteristic skin lesion distinctively seen on dermoscopy.

Inflammation and thrombo-occlusive vessel signalling in benign atrophic papulosis (Köhlmeier-Degos disease).

BACKGROUND: Although the merely cutaneous, benign form of the extremely rare disease atrophic papulosis (Köhlmeier-Degos disease) may occasionally develop into the systemic, malignant form with time, it is unclear whether it exhibits any systemic characteristics. OBJECTIVE: To determine whether benign atrophic papulosis exhibits inflammatory and thrombo-occlusive signals and to classify it according to the Chapel-Hill classification of vasculitis. METHODS: In a monocentric, controlled study, levels of cytokines (IL-1ß, IL-6, IL-8, IFNγ, MCP-1, VEGF, TNFα, TGF-ß1), antiphospholipid antibodies (cardiolipin IgG/A/M, cardiolipin IgG, cardiolipin IgM, ß2-glycoprotein IgG/A/M, phosphatidyl choline, phosphatidyl serine, phosphatidyl inositol, phosphatidyl ethanolamine and sphingomyelin A), antibodies against proteinase-3 IgG and myeloperoxidase IgG, antinuclear antibodies and extractable nuclear antigen were assessed in blood samples of six benign atrophic papulosis patients and six age- and sex-matched healthy controls. RESULTS: IL-8 was only detectable in patients' serum. VEGF was reduced and cardiolipin IgG/A/M and ß2-glycoprotein antibodies were increased in the patients' group. ANA were only detected in three patients, and ENA were negative throughout. No differences were detected between the other investigated markers. CONCLUSIONS: This is the first study evaluating systemic inflammatory and thrombo-occlusive vessel signalling in benign atrophic papulosis and provides evidence of a non-antineutrophil cytoplasmatic antibodies immune-complex small vessel vasculitis according to the Chapel-Hill classification. These findings corroborate its systemic character despite the apparent missing involvement of systemic organs.

Exploring the pathophysiologic basis of constrictive pericarditis of Kohlmeier Degos disease: A case series and review of the literature.

Kohlmeier-Degos Disease is a unique thrombotic microvascular and arteriopathic vasculopathy that is highly selective in the organs it targets. It invariably involves the skin and can be a purely cutaneous process. It affects both the microvasculature and the arterial system ranging from a thrombogenic microangiopathy to a fibrointimal obliterative arteriopathy with an accompanying background of extravascular fibrosis. A potentially lethal complication of Kohlmeier-Degos disease is constrictive pericarditis and pleuritis. We present three male patients, ages 26 years, 46 years and 58 years of age with established cutaneous and gastrointestinal Kohlmeier-Degos disease who developed progressive pericarditis which in two necessitated a pericardiectomy. There are 6 other reported cases, 5 in men, with restrictive symptoms developing on average 6 years following the onset of skin disease and all with gastrointestinal involvement. Half of the patients died within one year following the diagnosis of cardiopulmonary restrictive disease. The restrictive symptoms developed within 12 months, 2 years and 11 years following the initial skin presentation. In one patient this complication developed despite receiving eculizumab, indicative that this extravascular fibrosing reaction was not complement mediated as opposed to the thrombotic microvascular component of the disease which is C5b-9 mediated. Two of the three patients had evidence of right ventricular dysfunction. Two of our patients died within 1 year of developing constrictive pericarditis due to progressive cardiopulmonary failure. A profibrogenic process resembling scleroderma was seen given the degree of smooth muscle actin staining along with a mirror image reduction in CD34 expression within the fibrotic pleura and pericardium. There was significant upregulation in type I interferon signaling in cases tested as revealed by the degree of staining for MXA, the surrogate type I interferon marker. We propose that excessive type I interferon signaling results in the influx of monocyte derived dendritic cells with subsequent transdifferentiation into potent collagen producing myofibroblasts. We believe that targeting and suppressing type I interferon signaling should be a cornerstone of early therapy in patients with Kohlmeier- Degos disease to prevent pleural and pericardial fibrosis.

Degos disease: A radiological-pathological correlation of the neuroradiological aspects of the disease.

Malignant atrophic papulosis (Degos disease) is an unusual thrombotic microangiopathy of uncertain etiology. The disease characteristically involves the skin and internal organs, with nervous system involvement more common in children. We present a case with diverse neurological manifestations including cranial nerve palsies, gait instability, and urinary incontinence. The patient also developed white papular lesions on her lower extremities and back. Magnetic resonance imaging (MRI) demonstrated progressive intracranial and spinal abnormalities. Despite treatment with numerous biologic agents, the patient had persistent clinical deterioration and expired one month after admission. We highlight the extensive neurologic manifestations of Degos disease correlated with neuroradiological imaging and pathological features. Nervous system involvement in Degos disease requires careful neurologic and dermatologic exam with central nervous system (CNS) magnetic resonance imaging to distinguish it from non-organic etiologies of similar symptoms.

Diffuse atrophic papules and plaques, intermittent abdominal pain, paresthesias, and cardiac abnormalities in a 55-year-old woman.

KEY TEACHING POINTS.

Laparoscopy shows superiority over endoscopy for early detection of malignant atrophic papulosis gastrointestinal complications: a case report and review of literature.

BACKGROUND: The malignant form of atrophic papulosis (Köhlmeier-Degos disease) is a rare thrombo-occlusive vasculopathy that can affect multiple organ systems. Patients typically present with distinctive skin lesions reflective of vascular drop out. The small bowel is the most common internal organ involved, resulting in considerable morbidity and mortality attributable to ischemic microperforations. Determination of the presence of gastrointestinal lesions is critical in distinguishing systemic from the benign, cutaneous only disease and in identifying candidates for treatment. CASE PRESENTATION: We describe an 18 year old male who first presented with cutaneous atrophic papulosis but became critically ill from small bowel microperforations. He had an almost immediate and dramatic response to treatment. Prior to his presentation with acute abdomen he had upper and lower endoscopy showing areas of nonspecific patchy erythema. At laparotomy, innumerable characteristic lesions with central pearly hue and erythematous border were seen. PubMed was used for a literature search using the keywords malignant atrophic papulosis, Degos disease, endoscopy, laparoscopy and laparotomy. This search yielded 200 articles which were further analyzed for diagnostic procedures and findings. Among the 200 articles we identified only 11 cases in which endoscopy was performed. Results of endoscopy and laparotomy in our patient with malignant atrophic papulosis were compared to those in the literature. Endoscopy of the gastrointestinal tract has shown gastritis and non-specific inflammation whereas laparoscopy shows white plaques with red borders on the serosal surface of the small bowel and the peritoneum. From personal communications with other physicians worldwide, we identified three additional unpublished cases in which endoscopy revealed only minimal changes while laparoscopy showed dramatic lesions. From our experience the endoscopic findings are often subtle and nonspecific, whereas laparascopy or laparotomy will reveal pathognomic lesions on the serosal surface of the intestine. CONCLUSION: Our report contrasts the endoscopic and laparoscopic findings in malignant atrophic papulosis which suggest laparoscopy is the more powerful means of detecting gastrointestinal involvement. Imaging studies may serve as a key indicator of systemic progression. Based on our experience, laparoscopy should be performed when there is a high index of suspicion for gastrointestinal malignant atrophic papulosis, even if endoscopic examination is non-diagnostic or normal.

Malignant and benign forms of atrophic papulosis (Köhlmeier-Degos disease): systemic involvement determines the prognosis.

BACKGROUND: Atrophic papulosis (Köhlmeier-Degos disease) is a rare disease of unknown aetiology. The cutaneous signs--papular skin lesions with central porcelain-white atrophy and surrounding telangiectatic rim--are almost pathognomonic. Extracutaneous, systemic involvement includes multiple limited infarcts of the gastrointestinal system, central nervous system and other organs. OBJECTIVES: To assess prospectively the demographics, epidemiological data and prognosis of patients with atrophic papulosis evaluated in a single centre. METHODS: A prospective, single-centre, cohort study at diagnosis was performed on a series of 39 patients with atrophic papulosis, first seen between 2000 and 2007 and evaluated up to 2012. RESULTS: The occurrence of cutaneous lesions defined the onset of disease in all cases. The mean age of onset was 35.4 ± 12.3 years and the male-to-female ratio was 1 : 1.4. In total, 9% of patients reported familial occurrence. Extracutaneous (systemic) signs were recorded in 29% of the patients, whereas the median time for development of systemic manifestations was 1 year (0.03-0.97 quantiles: 0-7 years) after the occurrence of cutaneous lesions. The prognosis was determined mainly by the presence of systemic involvement. 73% of the patients with systemic manifestations (73% developed intestinal perforation) died, while none of the patients with only cutaneous disease had a lethal outcome. The cumulative 5-year survival rate in patients with systemic disease was 54.5%. CONCLUSIONS: Atrophic papulosis, previously called malignant atrophic papulosis, should be classified into a malignant, systemic form and a benign, cutaneous one, the latter being more common. The probability of having a benign form of the disease at onset is approximately 70%, increasing to 97% after 7 years of monosymptomatic cutaneous course.

Degos' syndrome complicated by bowel perforation: focus on radiological findings.

We describe a 50-year-old man who first presented with multiple skin lesions which were characteristic of Degos' syndrome. The patient developed multiple episodes of abdominal pain. Some episodes resolved with conservative management, for others he underwent urgent operations for bowel perforations. The patient subsequently underwent extensive small bowel resection, but further systemic deterioration ensued and he died. The imaging findings of Degos' syndrome and the implications of pneumatosis intestinalis and pneumoperitoneum are discussed.

Malignant Atrophic Papulosis Presenting with Intestinal Perforation: A Case Report.

Malignant atrophic papulosis sometimes known as Degos' disease is an idiopathic, uncommon condition with fewer than 200 occurrences documented. It is a chronic thrombo-obliterative vasculopathy characterised by papular skin lesions with a core porcelain-white atrophy and a surrounding telangiectatic border. We report a 15-year-old male patient with a recurrent history of hollow viscus perforation, which was managed on all the occasions with exploratory laparotomy and primary perforation repair. Additionally, the patient had a five month history of numerous, non-itchy, atrophic papules with a core porcelain-like area and hyperkeratotic margins, characteristic of Degos' disease. The only basis for diagnosis is the distinctive skin lesions with biopsy. Along with systemic lupus erythematosus and other connective tissue diseases, tuberculosis must also be taken into account while assessing the clinical presentation of malignant atrophic papulosis. There is currently no known treatment for malignant atrophic papulosis that has been effective. Keywords: case reports; intestinal perforation; malignant atrophic papulosis; ulcer; vasculitis.

Neurological Involvement in Malignant Atrophic Papulosis: A Comprehensive Review of Literature.

Malignant atrophic papulosis (MAP), or systemic Degos disease, is an obliterative vasculopathy of unknown origin, characterized by erythematous papules found on the skin, central nervous system (Neuro-MAP) and gastrointestinal tract. Neurological involvement occurs in approximately 20% of systemic cases, is progressive and largely fatal. It can be described in two forms: 1) the parenchymal presenting with meningoencephalitis and meningomyelitis and 2) the neurovascular presenting with large cerebral infarcts, intracranial and subarachnoid hemorrhage, subdural hematoma and venous sinus thrombosis. Predilection to subdural hematoma or hygroma is characteristic for neurological involvement in MAP in comparison to other vasculpathies and vasculitides. Peripheral nervous system manifestations are less common and include polyradiculopathy, neuropathy, and myopathy. CSF analysis usually shows mild to moderate pleocytosis, increased protein content, and normal glucose. Brain MRI may reveal cortical, subcortical and deep white matter ischemic lesions with possible nodular, leptomeningeal, dural, or ependymal enhancement. Spinal cord MRI may reveal patchy lesions from the periphery to the center or cord atrophy in progressive course. Neurological involvement in MAP has a grave prognosis. The interval from onset of papulosis to death averages two years in patients with neurological involvement. There is no confirmed treatment for MAP but there are promising reports with eculizumab and treprostinil.