Atrophic papulosis (Köhlmeier-Degos disease): Diagnosis and management

INTRODUCTION — 

Atrophic papulosis (also known as Köhlmeier-Degos disease or Degos disease) is a rare and potentially life-threatening nonvasculitic vasculopathy. The disorder can affect only the skin (also known as benign atrophic papulosis) or multiple organ systems (also known as malignant atrophic papulosis) (picture 1A-D). The gastrointestinal tract and central nervous system are the most frequent sites of systemic involvement. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Terminology'.)

Although skin-limited involvement is not associated with increased mortality, death related to systemic involvement is common. Early recognition of atrophic papulosis helps to identify patients who may benefit from treatment. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Prognosis'.)

The diagnosis and management of atrophic papulosis will be reviewed here. The epidemiology, clinical manifestations, and prognosis of this disorder are reviewed separately.

●(See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis".)

DIAGNOSIS — 

A diagnosis of atrophic papulosis is usually first suspected after the detection of characteristic skin lesions (porcelain-white papules with erythematous telangiectatic borders (picture 1D and picture 1A-C)). In individuals with darkly pigmented skin, the central porcelain white region can demonstrate hyperpigmentation in the rim [1]. Diagnosis is often delayed due to the nonpruritic and painless nature of the lesions. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Skin'.)

General approach — Cutaneous involvement usually occurs before or in conjunction with systemic involvement. In these patients, the diagnosis can be confirmed based on the presence of characteristic skin lesions (with or without evidence of systemic involvement), consistent skin biopsy findings, and the exclusion of other disorders. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Clinical manifestations' and 'Skin biopsy' below.)

Patients with cutaneous findings consistent with atrophic papulosis should be evaluated for extracutaneous involvement. (See 'Additional evaluation' below.)

Occasionally, the pathognomonic skin lesions are absent. In their absence, a diagnosis of systemic disease may reasonably be made based on the detection of characteristic serosal lesions on laparoscopy, provided other disorders are excluded.

Skin biopsy — All patients with atrophic papulosis-like skin lesions should undergo a skin biopsy to confirm the diagnosis. A 4 mm punch biopsy extending into the subcutaneous fat is usually sufficient. Alternatives include a larger punch biopsy or a small wedge biopsy. The preferred site for a lesional biopsy is the border of the central porcelain-white area and the telangiectatic rim (picture 1A). (See "Skin biopsy techniques", section on 'Punch biopsy'.)

The supportive histopathologic findings are reviewed separately. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Histopathology'.)

ADDITIONAL EVALUATION — 

Prompt assessment for manifestations of systemic disease may help identify patients who may benefit from treatment prior to life-threatening complications.

Our approach — Our initial assessment typically includes a review of systems, physical examination, laparoscopy, and select laboratory tests.

If the findings suggest systemic involvement, further evaluation will be indicated. (See 'Patients with positive laparoscopy' below and 'Patients with neurologic symptoms' below.)

Review of systems — The review of systems should include particular attention to the gastrointestinal, central nervous, respiratory, and renal systems. Key symptoms we inquire about include:

●Abdominal pain

●Headache

●Visual changes

●Focal neurologic symptoms (weakness, altered sensation)

●Pulmonary complaints (eg, dyspnea, chest pain)

●Hematuria

Physical examination — We perform a careful physical examination.

●Slit lamp examination of the eyes for findings such as conjunctival atrophic plaques, telangiectatic vessels, papilledema, and optic atrophy

●Full skin examination for characteristic lesions

●Pulmonary examination for pleural effusion

●Abdominal examination for tenderness

Laboratory and radiologic tests — Laboratory testing and a chest radiograph are performed to detect findings suggestive of extracutaneous involvement. Our initial approach typically includes:

●Complete blood count

●Comprehensive metabolic panel

●Erythrocyte sedimentation rate (if abnormal in early atrophic papulosis, may suggest other diagnoses)

●Stool test for occult blood

●Urinalysis to assess for signs of kidney dysfunction (blood, protein/creatinine ratio) and/or bladder involvement

●Chest radiographs (posteroanterior and lateral) to assess for pleural effusion

Laparoscopy — Laparoscopy is the gold standard for early diagnosis of systemic disease. However, experts disagree on whether laparoscopy should be performed in all patients with newly diagnosed cutaneous atrophic papulosis or only in patients with concomitant abdominal pain or symptoms.

●Our approach – Our practice is to refer all patients with clinical and histopathologic findings consistent with skin lesions of atrophic papulosis for laparoscopy because of our preference to treat gastrointestinal involvement as early as feasible. This includes patients without abdominal pain or symptoms. Bowel lesions can be asymptomatic at the time of visualization. Children in particular may benefit from early laparoscopy, since they are often diagnosed in a later stage of disease compared with adults. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Gastrointestinal tract' and 'Gastrointestinal involvement' below.)

Laparoscopy is less invasive than laparotomy and is the preferred diagnostic modality. (See "Abdominal access techniques used in laparoscopic surgery".)

●Supportive findings – Laparoscopy findings that support a diagnosis of atrophic papulosis include characteristic flat; irregularly bordered; porcelain white, off-white, or yellow plaques on the serosa of the intestines, peritoneum, or other abdominal organs. Other findings may include areas of edema, ischemia, or shallow ulceration on the serosa. In most cases, a serosal biopsy is not needed and should probably be avoided. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Gastrointestinal tract'.)

Patients with positive laparoscopy — Our suspicion for additional sites of extracutaneous involvement increases when laparoscopy identifies findings consistent with atrophic papulosis. In this scenario or when other signs or symptoms raise suspicion for extraintestinal involvement, we perform additional tests to assess for other sites of internal disease.

In addition to our routine initial laboratory tests (see 'Laboratory and radiologic tests' above), we obtain:

●Brain magnetic resonance imaging (MRI) to assess for neurologic abnormalities

●Baseline electrocardiogram and echocardiogram to assess for pericardial thickening or effusion

Patients with negative laparoscopy — When laparoscopy is negative and the review of symptoms, physical examination, and routine laboratory tests do not detect abnormalities suggestive of systemic disease, we assume the patient has skin-limited disease. However, these patients require close clinical follow-up to detect findings suggestive of progression to systemic disease. (See 'Patient counseling and follow-up' below.)

Patients with neurologic symptoms — We refer patients with neurologic symptoms to a neurologist for further evaluation. We typically obtain MRI of the brain as a preliminary study for patients with symptoms of headache. A spine MRI may also be appropriate in patients with symptoms suggestive of spinal involvement. Other tests, such as lumbar puncture for cerebrospinal fluid analysis (cytology, protein, glucose, and infection-related studies if indicated), should be performed in patients with an abnormal brain MRI and/or angiography, provided contraindications to lumbar puncture have been excluded. (See "Lumbar puncture: Technique, contraindications, and complications in adults", section on 'Contraindications and precautions for high-risk patients'.)

Role of other tests — Abdominal radiologic imaging and endoscopy may show abnormalities in patients with gastrointestinal involvement, but the findings are nonspecific and have limited utility for diagnosis.

●Endoscopy – Endoscopy is generally reserved for cases in which it is needed to evaluate for other causes of abdominal symptoms. Upper and lower endoscopy studies are often normal in atrophic papulosis and are considered inferior to laparoscopy for diagnosis [2]. In advanced gastrointestinal disease, endoscopy may show ulceration or patchy erythema. Rarely, colonoscopy will demonstrate luminal strictures [3].

DIFFERENTIAL DIAGNOSIS — 

A diagnosis of atrophic papulosis requires the exclusion of other disorders that may mimic this disease.

Because early skin lesions of atrophic papulosis are nondescript inflammatory papules, it can be difficult to clinically distinguish them from other inflammatory skin disorders. Histopathologic confirmation can also be difficult at this stage. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Skin'.)

The differential diagnosis for established cutaneous lesions includes other disorders that may present with depigmented and/or atrophic macules on the skin. Examples include:

●Atrophic blanche in livedoid vasculopathy – Livedoid vasculopathy is a thrombo-occlusive cutaneous vasculopathy that commonly presents with atrophie blanche, a skin finding characterized by white or hypopigmented atrophic plaques surrounded by hyperpigmentation and telangiectasias (picture 2). Livedoid vasculopathy typically involves the lower legs. Additional skin findings include livedoid skin changes and ulceration.

A skin biopsy demonstrating intraluminal thrombosis, endothelial proliferation, and subintimal hyaline degeneration supports the diagnosis. Livedoid vasculopathy can occur independently or in association with antiphospholipid syndrome, systemic lupus erythematosus, or other rheumatic diseases. (See "Livedoid vasculopathy".)

●Extragenital lichen sclerosus – Extragenital lichen sclerosus is a chronic inflammatory skin disorder that can present with white or hypopigmented, atrophic papules or plaques with a wrinkled appearance (picture 3A-B). Telangiectasia, follicular keratotic plugs, or hemorrhagic bullae may also be present. Common sites for involvement include the neck, trunk, and extremities. Lichen sclerosus may also involve the genital areas.

The diagnosis can often be made based on the clinical appearance. Skin biopsy findings can confirm the diagnosis when needed. (See "Extragenital lichen sclerosus: Clinical features and diagnosis".)

●Vitiligo – Vitiligo is an acquired disorder of pigmentation characterized by the development of depigmented macules or patches on the skin (picture 4A-B). Clinical signs of inflammation are generally absent. Vitiligo can affect any body site. Features of cutaneous atrophy are absent. (See "Vitiligo: Pathogenesis, clinical features, and diagnosis", section on 'Clinical features'.)

●Idiopathic guttate hypomelanosis – Idiopathic guttate hypomelanosis is a common disorder that presents with small depigmented macules on the skin (picture 5A-B). These asymptomatic skin lesions commonly occur on sun-exposed areas, such as the legs and forearms. The condition primarily occurs in middle-aged or older adults.

●Molluscum contagiosum – Molluscum contagiosum is a skin-limited viral infection that presents with small, skin-colored, umbilicated papules (picture 6A-B). A white core may be visible in the center of molluscum lesions. (See "Molluscum contagiosum".)

●Primary angiitis of the central nervous system – Findings of primary angiitis of the central nervous system may be confused with atrophic papulosis in patients without characteristic atrophic papulosis skin lesions. Both disorders can present with headache and can subsequently demonstrate subdural hygromas, leptomeningeal enhancement on MRI, normal magnetic resonance angiography (MRA), infarcts, hemiparesis, and angiographic irregularity in the circle of Willis [4]. (See "Primary angiitis of the central nervous system in adults" and "Childhood primary angiitis of the central nervous system: Angiography-negative subtype".)

Atrophic papulosis-like lesions have been reported in patients with rheumatic disorders, such as systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Associated disorders'.)

A broader differential diagnosis for acquired hypopigmented skin lesions is reviewed separately. (See "Acquired hypopigmentation disorders other than vitiligo".)

MANAGEMENT — 

The management of atrophic papulosis is evolving and there is no established standard of care. Treatment efficacy data are primarily limited to case reports and small case series.

Our approach is described here. Other approaches may be reasonable.

Goals — Atrophic papulosis is a potentially life-threatening disorder. Early recognition of systemic involvement is considered important to identify patients who may benefit from treatment. The major goals of treatment are to limit further tissue damage, preserve organ function, and reduce morbidity and mortality. (See 'Systemic disease' below.)

Treatment of skin-limited disease is optional. When treatment is implemented for skin-limited disease, the primary goal is to improve skin lesions. No drug has been proven to reliably diminish or eliminate the risk of progression to systemic disease. (See 'Skin-limited disease' below.)

Response assessment — The response of systemic involvement to therapy is generally assessed through clinical findings, such as improvement in symptoms of abdominal pain or improvement in patient status (eg, improved stability of a critically ill patient). Improvement in laparoscopic or radiologic evidence of disease has also been reported [5].

Physical examination is sufficient for assessing the response of skin disease.

Meningococcal vaccine — All patients diagnosed with atrophic papulosis must receive meningococcal vaccination if they are not up to date with the primary dose and boosters (table 1). Meningococcal vaccination is indicated for treatment with complement inhibitors such as eculizumab, a major treatment option for systemic involvement in atrophic papulosis. The terminal complement pathway is essential for protection against Neisseria infections. (See "Meningococcal vaccination in children and adults", section on 'Target groups' and 'Combination eculizumab and treprostinil' below.)

Skin-limited disease

Our approach — We do not typically treat skin-only involvement. It is unclear whether treatment of skin-limited disease has any impact on the risk of progression to systemic disease, and efficacy data for treatments for skin-limited disease are limited.

Skin lesions are asymptomatic for most patients; when necessary, we manage pruritus with antipruritic agents. (See "Pruritus: Therapies for localized pruritus".)

For patients who desire treatment to improve skin lesions, a trial of antiplatelet therapy, such as aspirin, can be reasonable. However, the risks of treatment should be carefully considered. (See 'Antiplatelet and anticoagulant drugs' below.)

Antiplatelet and anticoagulant drugs — Because thrombosis is a pathologic feature in involved tissues, antiplatelet agents and anticoagulants have been used for treatment. However, the efficacy of these interventions has not been assessed in randomized trials, and the best approach to treatment is unclear. (See "Platelet biology and mechanism of anti-platelet drugs", section on 'Anti-platelet drugs'.)

Limited data suggest that aspirin may be a reasonable initial choice for patients who will proceed with therapy.

●In a 2020 systematic review of the literature, antiplatelet therapies were the most commonly employed treatment. Among the 26 reports of patients who received antiplatelet agents only (typically aspirin alone or in combination with dipyridamole) for skin-limited disease, 11 (42 percent) had documentation of complete resolution and 4 (15 percent) had partial resolution [6]. Aspirin (from 81 to 325 mg per day) was used in all patients who achieved a complete response to antiplatelet monotherapy. Complete and partial responses to nonantiplatelet anticoagulant monotherapy (the second most common regimen) occurred in one out of six (17 percent) and two out of six patients (33 percent), respectively.

Adverse effects of aspirin are reviewed in detail separately. (See "Nonselective NSAIDs: Overview of adverse effects".)

Other therapies — Data on other therapies for skin involvement are limited. Isolated reports describe both improvement and treatment failure with systemic glucocorticoid or vasodilator therapy [6].

Although improvement in skin lesions has been reported in some patients treated with eculizumab or treprostinil for systemic involvement, these therapies are not typically utilized for skin-limited disease [5,7]. (See 'Systemic disease' below.)

Patient counseling and follow-up — We counsel patients presenting with skin-limited disease about the possibility of subsequent development of systemic disease. We encourage prompt clinical follow-up for gastrointestinal, neurologic, ocular, or other symptoms without an immediately identifiable alternative cause. In addition, we advise patients to inform health care providers of their diagnosis of atrophic papulosis. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Disease course'.)

Close clinical follow-up (physical examination and review of systems) to assess for signs or symptoms of progression to systemic disease is warranted, regardless of whether treatment is initiated. We typically follow these patients every three months for the first year and then at least twice yearly thereafter. The need for further testing is based on the findings of the clinical assessment. The risk for systemic involvement seems to decrease over time. (See "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Disease course'.)

Systemic disease

Gastrointestinal involvement — Eculizumab (a C5 inhibitor) and treprostinil (a prostacyclin analog) are the mainstays of therapy for gastrointestinal involvement. (See 'Combination eculizumab and treprostinil' below.)

Combination eculizumab and treprostinil — We aim to start all patients with laparoscopic evidence of gastrointestinal involvement on eculizumab promptly, even in the absence of symptoms. Whenever feasible, we add treprostinil therapy. In our experience, treatment of gastrointestinal lesions with eculizumab before perforation seems to be associated with prolonged symptom-free survival in patients without other sites of systemic involvement.

Ravulizumab may be an alternative to eculizumab that requires less frequent dosing. (See 'Other C5 inhibitors' below.)

Our preference for combination therapy is based on case reports that describe rapid symptom improvement after the initiation of eculizumab and improvement in persistent or recurrent symptoms after the addition of treprostinil. (See 'Eculizumab' below and 'Treprostinil' below.)

The high cost of eculizumab may inhibit access in some settings. In the United States, intensive advocacy is often required to obtain therapy. Alternative C5 treatment strategies (eg, ravulizumab and crovalimab) may provide less expensive alternatives.

Eculizumab — Eculizumab is a monoclonal antibody that blocks the terminal complement pathway by binding to C5. Eculizumab appears to prevent C5b-9 membrane attack complex-mediated endothelial injury.

●Administration and precautions – Eculizumab is administered through intravenous infusion. Dosing for atrophic papulosis is not standardized.

Our approach resembles the regimen used for neuromyelitis optica spectrum disorder, with a slightly higher initiating dose.

Adults receive:

•1200 mg initial dose on day 0

•900 mg on days 7, 14, and 21

•1200 mg on day 28 and every two weeks thereafter

Pediatric dosing is weight based.

Eculizumab increases the risk of infection with Neisseria meningitidis. Thus, the meningococcal vaccine (primary or booster doses) should be administered immediately to patients who are not up-to-date with this vaccine (table 1). Patients should also receive prophylactic antibiotic therapy. In the United States, treatment with eculizumab requires participation in a Risk Evaluation and Mitigation Strategy (REMS) program due to the risks of Neisseria infection. (See 'Meningococcal vaccine' above and "Meningococcal vaccination in children and adults" and "Treatment and prevention of meningococcal infection", section on 'Patients receiving C5 inhibitors'.)

●Efficacy – Efficacy data for eculizumab for gastrointestinal involvement are limited to observations of individual patients. Rapid resolution of abdominal pain (eg, within the first few days to two weeks of treatment) has occurred after the initiation of eculizumab [5,8,9]. In our experience, in some patients with repeated perforations, initiation of eculizumab infusions has been associated with rapid stabilization and cessation of new perforations.

The frequent delay in the diagnosis of atrophic papulosis until the occurrence of life-threatening complications or treatment delays related to accessibility of eculizumab might contribute to treatment failures [10,11].

In patients who improve, clinical experience suggests that continued treatment may be necessary to maintain stability. Symptom recurrence or disease progression despite continued treatment with eculizumab without treprostinil has also been reported [5,9,10].

Treprostinil — Treprostinil is a prostacyclin analog used for the treatment of pulmonary hypertension that induces vasodilation and inhibits platelet aggregation. It is postulated that treprostinil may improve abdominal symptoms and reduce risk of further intestinal perforation by enhancing blood flow to affected tissue. In children with idiopathic pulmonary hypertension, treprostinil appears to boost the density of endothelial progenitor cells in the arterioles [12].

●Administration and precautions – Treprostinil is typically given in conjunction with eculizumab, as the drug has not been associated with benefit when used as monotherapy.

Treprostinil can be given subcutaneously through an infusion pump, orally, or intravenously. We prefer subcutaneous administration for patients with active gastrointestinal symptoms because of concern about variable absorption of oral treprostinil. Oral treatment is an alternative for patients with serosal lesions on laparoscopy but no active gastrointestinal symptoms. Intravenous treprostinil can be given to acutely ill or postsurgical hospitalized patients.

The initiation of treprostinil can be challenging; therefore, we typically manage treprostinil therapy in conjunction with a pulmonary hypertension specialist familiar with this drug. A reasonable initial subcutaneous or intravenous dose for adults is 1.25 ng/kg/minute by continuous infusion, as tolerated.

To reduce risk of adverse effects, the dose is gradually titrated up to a therapeutic level. Dose increases should not exceed 1.25 ng/kg/minute per week over the first four weeks. Subsequently, the dose can be increased by 2.5 ng/kg/minute each week up to a maximum of 40 ng/kg/minute.

Examples of common adverse effects include headaches, infusion site pain, loose stools, nausea, vomiting, and flushing.

●Efficacy – There are individual reports of patients with insufficient responses to eculizumab or progression following an initial response to eculizumab who have improved after the addition of treprostinil therapy [5,9]. Prolonged remission of gastrointestinal symptoms in association with combination therapy with subcutaneous or oral treprostinil and eculizumab has occurred in individual patients [5].

As an example, an adolescent patient with gastrointestinal involvement who had progression of symptoms after an initial response to eculizumab had resolution of abdominal pain, neurologic symptoms, and serosal lesions after the addition of treprostinil [5]. The patient also had improvement in brain MRI findings and gradual improvement in skin lesions.

Other therapies for systemic involvement — Multiple other therapies have been utilized in individual patients with systemic involvement with varying outcomes.

Eculizumab and treprostinil for nongastrointestinal involvement — The best approach to treating central nervous system involvement and other sites of extracutaneous involvement is unknown. There are isolated case reports of improvement in nongastrointestinal manifestations during treatment with eculizumab and treprostinil.

●Central nervous system – Compared with gastrointestinal involvement, eculizumab appears less effective for central nervous system involvement with reports of progression during eculizumab treatment. Potential explanations for this observation include different mechanisms of disease in the central nervous system or very limited cerebrospinal fluid penetration of eculizumab. In one patient, improvement in central nervous system symptoms and MRI findings occurred after the addition of treprostinil to eculizumab treatment [5].

●Other sites – In a case series, one patient treated with eculizumab and treprostinil had sustained improvement in pleural and pericardial effusions during treatment with eculizumab and treprostinil [13]. However, another patient had progression of pleural and pericardial involvement during treatment with eculizumab and oral treprostinil [13].

Antiplatelet and anticoagulant drugs — Antiplatelet and anticoagulant agents, such as aspirin, pentoxifylline, clopidogrel, ticlopidine, and heparin, have been used as primary or adjunctive therapies in patients with systemic involvement [6,14].

In a systematic review of published reports, 7 of 35 patients with systemic involvement (20 percent) given antiplatelet agent monotherapy had documentation of complete resolution, and 11 of 35 patients (31 percent) had documentation of partial resolution [6]. Among seven patients given anticoagulants as monotherapy, none had a complete response, and three of seven patients (43 percent) had documentation of partial resolution. The sites of systemic involvement were not specified.

Other C5 inhibitors — A shared mechanism of action suggests that other biologic C5 inhibitors may be alternatives for atrophic papulosis. However, there are no published reports of treatment with these agents.

●Ravulizumab and crovalimab – Ravulizumab is a C5 inhibitor that differs from eculizumab only in the substitution of four amino acids but has a fourfold longer half-life and achieves steady-state concentration more quickly. Consequently, ravulizumab may allow for less frequent intravenous dosing (eg, dosing every eight weeks in contrast to the every-two-week schedule for eculizumab).

Crovalimab is another anti-C5 monoclonal drug with an extended dosing interval (every four weeks) [15]. Efficacy of crovalimab for atrophic papulosis is uncertain.

●Avacopan and nomacopan – Avacopan and the investigational drug nomacopan are small molecule C5a receptor antagonists. These drugs have not been studied in atrophic papulosis, and based on mechanism of action, appear unlikely to reproduce the benefits of drugs like eculizumab, which block cleavage of the intact C5 substrate.

Other — Systemic glucocorticoids such as prednisone or methylprednisolone are sometimes used to suppress inflammation in atrophic papulosis. However, the efficacy of these agents varies. In a systematic review of published reports, 1 of 26 patients (4 percent) with systemic involvement treated with systemic glucocorticoid monotherapy had documentation of a complete response [6]. Partial responses were documented in seven patients (26 percent).

Various other therapies have been reported to improve atrophic papulosis in individual patients. Improvement with immunomodulatory therapies, such intravenous immune globulin [16,17] and cyclophosphamide [18], have been reported. A combination of rituximab and cyclophosphamide appeared beneficial in a patient with coincident atrophic papulosis and dermatomyositis [19]. There are also isolated reports of at least partial improvement with antibiotic, vasodilator, dextran, angiotensin-converting enzyme (ACE) inhibitor, and diuretic therapy [6].

Considerations for children — Treatment of atrophic papulosis in children is challenging, particularly given the higher incidence of central nervous system involvement in children compared with adults [20].

Other therapies with reports of benefit in children include baricitinib, anifrolumab, and bevacizumab. A child with atrophic papulosis with central nervous system involvement associated with an interferon receptor gene variant had improvement during treatment with baricitinib, and subsequently anifrolumab, after progression of the disease [21]. Signs of improvement occurred in a critically ill child treated with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), though the child ultimately died [22]. A lack of response to bevacizumab, natalizumab (a monoclonal antibody against the very late antigen-4 protein), or infliximab has been reported in other critically ill children with central nervous system involvement [4,22].

PATIENT AND CLINICIAN SUPPORT — 

The Malignant Atrophic Papulosis Support Network is a helpful resource for disease information, social support, and expert clinician resources.

SUMMARY AND RECOMMENDATIONS

●Disease overview – Atrophic papulosis (also known as Köhlmeier-Degos disease or Degos disease) is a rare, potentially fatal nonvasculitic vasculopathy that can involve only the skin or multiple organ systems. The characteristic skin lesions are porcelain-white papules with an erythematous telangiectatic border or hyperpigmented rim. (See 'Diagnosis' above and "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis", section on 'Skin'.)

The gastrointestinal and central nervous system are the most common sites of systemic involvement. Death most often results from complications related to gastrointestinal or neurologic involvement. (See 'Introduction' above and "Atrophic papulosis (Köhlmeier-Degos disease): Clinical manifestations, histopathology, and prognosis".)

●Diagnosis – Early recognition of atrophic papulosis is considered important to recognize patients who may benefit from treatment for active systemic disease. Often, the diagnosis can be made based on the recognition of pathognomonic skin lesions, consistent histopathologic findings, and the exclusion of other disorders. (See 'Diagnosis' above and 'Differential diagnosis' above.)

●Additional evaluation – Patients diagnosed with cutaneous lesions of atrophic papulosis require further evaluation to assess for systemic involvement. Our initial assessment usually consists of a review of systems, physical examination, and select laboratory tests. We also refer all patients for laparoscopy to assess for internal involvement. (See 'Additional evaluation' above.)

●Management – Although a wide variety of therapies have been utilized for atrophic papulosis, definitive treatment guidelines have not been established because efficacy data are limited.

•Patients with skin-limited disease – We do not treat skin-limited disease (skin disease without laparoscopic or other evidence of systemic involvement) in most patients. It is unclear whether treatment of skin-limited disease reduces risk for progression to systemic disease. Thus, the risks of treatment should be considered carefully. (See 'Skin-limited disease' above.)

For patients who desire a trial of treatment of skin-limited disease, we suggest initial treatment with aspirin rather than other therapies (Grade 2C). Improvement in skin lesions has been reported in patients treated with aspirin alone or in combination with other therapies. (See 'Antiplatelet and anticoagulant drugs' above.)

Patients with skin-limited disease require close clinical follow-up to assess for signs or symptoms of progression to systemic disease. (See 'Patient counseling and follow-up' above.)

•Patients with systemic involvement – The major goals of treatment of systemic involvement in atrophic papulosis are to limit further tissue damage, preserve organ function, and reduce morbidity and mortality. (See 'Systemic disease' above.)

For patients with laparoscopy findings supportive of gastrointestinal involvement, we suggest combination treatment with eculizumab and treprostinil rather than other therapies (Grade 2C). Rapid improvement has been observed after the initiation of eculizumab, and the addition of treprostinil has seemed to improve response in some patients. (See 'Gastrointestinal involvement' above.)