Malignant atrophic papulosis, otherwise known as Kohlmeier–Degos disease or Degos disease, is a rare disorder of thrombo-obliterative vasculopathy affecting the skin, gastrointestinal tract, and central nervous system. The characteristic papular skin lesions with central porcelain-white atrophy and a surrounding telangiectatic rim are considered pathognomonic. There are currently two forms of the disease described in the literature: a potentially life-threatening systemic form and a benign monosymptomatic cutaneous form. Thus, atrophic papulosis, rather than malignant atrophic papulosis, has been proposed as a more inclusive disease name. Subsequently, the disease would then get further subclassified into malignant systemic disease (malignant atrophic papulosis) and benign cutaneous disease (benign atrophic papulosis).
Despite having been first described in 1941 by Kohlmeier, the etiopathogenesis of atrophic papulosis remains elusive. There are theories of a genetic predisposition due to reports of atrophic papulosis among family members, including multiple generations. First-degree family members are more often affected, suggesting an autosomal dominant mode of inheritance.
Aside from a genetic predisposition, there are three main hypotheses suggested as the etiology of the disease: vasculitis, coagulopathy, and a primary dysfunction of the endothelial cells. These previously mentioned postulations are likely not mutually exclusive and occur in the setting of environmental factors creating the appropriate condition.
Atrophic papulosis usually first manifests between the second and fifth decades of life. There have also been single case reports of atrophic papulosis occurring in newborns. There is a slight female preponderance. However, there appears to be no sex-associated prognosis despite earlier suggestions in literature.
As previously mentioned, there are three proposed theories for the pathogenesis of atrophic papulosis: vasculitis, coagulopathy, and a primary dysfunction of the endothelial cells. Su et al. described a “lymphocyte-associated necrotic vasculitis” as the dominating cutaneous feature of the skin lesions. This led to some to postulate that this inflammation-driven process serves as the nidus for the disease. Magro et al. discovered prominent deposits of C5b-9 in the skin, gastrointestinal tract, and cerebral vasculature of some atrophic papulosis patients. Also, all of the patients with high C5b-9 deposition had high expressions of interferon-a, endothelial tubuloreticular inclusions, and an interferon gene signature in peripheral blood mononuclear cells.
Other authors have observed fibrinolytic dysfunction in select patients, with the main inciting event being a thrombus in the deep, reticular dermis. The resulting ischemia causes damage to the endothelial cells, leading to mucin deposition and mononuclear cell aggregation. Furthermore, increased activity of plasminogen activator inhibitor-1 decreased serum plasminogen levels, and persistent increases in thrombin-antithrombin III and plasmin-a-2 plasmin inhibitor complexes also support coagulopathy as a potential etiology.
Lastly, Tribble et al. suggested an abnormal swelling and proliferation of the vascular endothelium triggers cutaneous, gastrointestinal, and central nervous system thrombosis. This theory appears to be supported by findings on electron microscopy. Furthermore, a viral or bacterial infection could be the origin of these endothelial cell changes, a concept with support from the discovery of intracytoplasmic paramyxovirus-like inclusions on electron microscopy in skin lesions of atrophic papulosis patients. However, there has been no polymerase chain reaction evidence of paramyxovirus DNA in biopsy specimens.
On histopathology, lesions show a wedge-shaped area of the ischemic dermis with a sparse perivascular lymphohistiocytic infiltrates at the edge of the ischemic area. There is also an atrophic and slightly hyperkeratotic overlying epidermis. Within the dermis, edema and mucin deposition may be found in earlier lesions, whereas sclerosis is often present in later lesions. Early lesions may resemble lupus erythematosus, while later lesions resemble lichen simplex chronicus atrophicus. Vascular damage with thrombosis may occur at the base of the lesion.
Cutaneous lesions initially appear as small (2.0 to 5.0 mm) erythematous papules on the trunk or extremities. Over 2 to 4 weeks, the center of the lesion depresses, and lesions evolve into the pathognomonic large papules (0.5 to 1.0 cm) with an atrophic porcelain-white center and an erythematous, telangiectatic rim. The palms, soles, scalp, and face are rarely involved.
In those who develop extracutaneous involvement, the systemic disease can develop suddenly or many years after cutaneous manifestations. Patients may report upper or lower gastrointestinal tract bleeding, abdominal pain, numbness and tingling, vision changes, and respiratory or cardiac symptoms depending on the organs involved.
The basis of diagnosis is on finding the pathognomonic skin lesions on physical exam and can be supported histopathologically. There are no lab abnormalities or serum markers specific for atrophic papulosis identification. However, many patients present with defects in blood coagulation.
If organ symptomatology is suspected, the evaluation focuses on the organ involved. For instance, gastrointestinal involvement may require a fecal occult blood test, colonoscopy, esophagogastroduodenoscopy, or laparoscopy. Brain magnetic resonance imaging with contrast, heart ultrasonography, thorax computed tomography with contrast, ocular fundus examination, and kidney function tests are recommendations for the central nervous system, cardiac, respiratory, ocular, or renal involvement, respectively.
There is no proven treatment effective for atrophic papulosis. Anticoagulants and medications that facilitate blood perfusion, including acetylsalicylic acid, pentoxifylline, dipyridamole, ticlopidine, and heparin, have achieved partial regression of skin lesions in single cases. Thus, they are a reasonable first-line therapeutic approach in newly diagnosed patients. Eculizumab, which decreases C5b-9 membrane attack complex deposition, improved initial cutaneous and intestinal lesions but did not hinder the development or progression of systemic disease. Subcutaneous treprostinil was successful in a case of eculizumab-resistant malignant atrophic papulosis with intestinal and cerebral manifestations. Fibrinolytic and immunosuppressive therapy with cyclosporine A, azathioprine, cyclophosphamide, or corticosteroids have been unsuccessful.
Due to the severe and potentially life-threatening variant of the disease, annual follow-up is mandatory. Some authors even recommend following up biannually for the first seven years of disease and then annually thereafter. Monitoring should include skin examination, brain magnetic resonance tomography, gastroscopy, colonoscopy, chest x-ray, and an abdominal ultrasound to assess long-term prognosis.
A single-center cohort study of 39 patients determined the probability of having the benign cutaneous form of the disease was 70%. The likelihood of benign disease increased to 97% after a 7-year duration of skin-limited disease. No patients with cutaneous-limited disease had a lethal outcome. In contrast, the overall mortality in the systemic disease was 21%, with a mean survival time of 0 to 9 years. This finding differed from a 1989 literature review of 109 patients, which estimated overall mortality of 48.1% with a mean survival time of fewer than five years.
The high mortality rate of malignant atrophic papulosis is associated with the severe complications arising from systemic organ involvement. The most commonly involved organ systems are the gastrointestinal tract (73%), followed by the central nervous system (64%) and multiple organ systems (64%). The majority of fatalities are due to bowel perforation, cerebral artery thrombosis, or massive cerebral hemorrhage. Peritonitis, meningitis, encephalitis, radiculopathy, and myelitis are also significant causes of patient morbidity and mortality. Other serious complications include pleuritis, pericarditis, diplopia, and ophthalmoplegia.
It is essential to educate patients on the potential symptoms that can arise in serious systemic disease. Early detection of organ involvement may prevent the occurrence of severe complications and subsequent mortality.
Due to the high potential mortality of the malignant variant of atrophic papulosis, a collaborative approach is necessary for the management of these patients.
When physicians come across genetic skin disorders, the key is to refer them to a dermatologist for further workup. The disorder has associations with malignancies, and the referral should be without delay
Dermatologists must work in tandem with primary care physicians, gastroenterologists, pulmonologists, cardiologists, and ophthalmologists to provide patients with the appropriate screening and health care of patients with malignant atrophic papulosis.
While there is no definitive pharmaceutical treatment for atrophic papulosis, the medications used in management should have pharmacist input, both for dosing as well as medication reconciliation, to minimize potential adverse effects and drug-drug interactions. The pharmacists should report any concerns to the managing clinician or the nursing staff for action.
Nursing will see the patient at every visit and can monitor for medication compliance, note treatment progress or lack thereof, and provide counsel and education to the patient and family. Again, this information must be shared with the entire health care team.
As can be seen from the above atrophic papulosis requires an interprofessional team approach, including physicians, specialists, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level 5]
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