August 2025
INTRODUCTION —
Atrophic papulosis (also known as Köhlmeier-Degos disease or Degos disease) is a rare and potentially fatal nonvasculitic vasculopathy characterized by occlusion of small- and medium-sized arteries and veins. The disorder may affect only the skin or multiple organ systems. The exact pathogenesis is unknown.
Atrophic papulosis occurs in both adults and children. Many patients demonstrate only the pathognomonic skin findings (porcelain-white papules with erythematous telangiectatic borders (picture 1A-D)) and never progress to systemic disease. The gastrointestinal tract and central nervous system are the most common sites of extracutaneous disease.
The clinical features, histopathology, and prognosis of atrophic papulosis will be reviewed here. The diagnosis and management of this condition are reviewed separately. (See "Atrophic papulosis (Köhlmeier-Degos disease): Diagnosis and management".)
TERMINOLOGY —
The terms "benign atrophic papulosis" and "malignant atrophic papulosis" can be used to refer to skin-only presentations and extracutaneous presentations of atrophic papulosis, respectively.
Köhlmeier-Degos disease and Degos disease are alternative names for atrophic papulosis derived from two clinicians who played critical roles in the discovery of this disorder. In 1941, Walter Köhlmeier, a pathologist in Vienna, reported the first case of a systemic disease with features consistent with atrophic papulosis [1]. Köhlmeier attributed the condition to an unusual form of thromboangiitis obliterans (Buerger disease). (See "Thromboangiitis obliterans (Buerger disease)".)
Robert Degos, a dermatologist in France, recognized the uniqueness of the diagnosis and in February 1942 reported what "seems to be an as yet undescribed dermatosis" to a meeting of the French Society of Dermatology [2]. In 1948, Degos proposed the name "malignant atrophic papulosis" to emphasize the fatal prognosis.
Atrophic papulosis is distinct from Dowling-Degos disease, a rare genetic disorder characterized by cutaneous hyperpigmentation. (See "Congenital and inherited hyperpigmentation disorders", section on 'Dowling-Degos disease'.)
CLASSIFICATION —
Atrophic papulosis is a nonvasculitic vasculopathy, lacking the destruction of the internal elastic lamina in arteries and arterioles that is an essential finding in vasculitis [3]. (See "Evaluation of adults with cutaneous lesions of vasculitis".)
The strong type 1 interferon signature detected in active atrophic papulosis lesions suggests the possibility that the disease is an interferonopathy (at least in familial variants of the disease) [4]. Alternatively, atrophic papulosis might represent a phenocopy of the interferonopathies (ie, immune defects caused by somatic mutation rather than inherited inborn errors of immunity) [5]. (See 'Pathogenesis' below and "Autoinflammatory diseases mediated by interferon production and signaling (interferonopathies)".)
PATHOGENESIS —
Limited data preclude definitive conclusions on the etiology and pathophysiology of atrophic papulosis. However, several factors have been proposed as potential contributors, primarily based on findings in individual patients.
●Genetic predisposition – Some familial clustering has been reported, with first-degree relatives more frequently affected, suggesting the possibility of autosomal dominant inheritance [6-8]. In addition, a heterozygous de novo gain-of-function variant in the interferon alpha/beta receptor subunit 1 gene (IFNAR1; MIM #107450) has been reported in a child with atrophic papulosis [9].
●Endothelial injury, interferon, and complement – Endothelial cells are the main target of injury in atrophic papulosis. Endothelial dysfunction may impair vasodilation, promote platelet aggregation, and facilitate thrombus formation [10].
Interferon-alpha-mediated deposition of C5b-9 (the membranolytic attack complex) in the vasculature is postulated to play a role in microvascular injury in atrophic papulosis [4]. Findings supportive of high interferon-alpha expression (ie, high expression of human myxovirus resistance protein A [MxA]) and prominent deposition of complement terminal C5b-9 complex (also known as the membrane attack complex) have been detected in affected tissues from patients with atrophic papulosis [4,11,12]. There is also a case report describing the development of typical atrophic papulosis skin lesions and aseptic leptomeningitis after treatment with type 1 interferon [13].
Some authors have drawn parallels between the pathogenesis of atrophic papulosis and coronavirus disease 2019 (COVID-19) [14]. The complement activation seen in atrophic papulosis (C5b-9 deposition) is present in adults with COVID-19 and appears to play a significant role in organ failure among adults with severe COVID-19 infection [15].
●Other immune dysfunction – Other forms of immune dysregulation are supported by the presence of increased levels of interleukin (IL) 6, tumor necrosis factor (TNF)-alpha, and anticardiolipin antibodies in patients with atrophic papulosis [16]. These may in turn contribute to increased activity of plasminogen activator inhibitor 1 (PAI1), decreased serum plasminogen levels, and increased thrombin-antithrombin III and alpha-2 antiplasmin inhibitor complexes, leading to thrombosis at the site of the damaged endothelium [17,18].
Certain factors suggest that autoantibody production is not a driving factor for atrophic papulosis. These include the absence of antibody deposition in atrophic papulosis lesions and the lack of benefit from therapies such as plasmapheresis, rituximab, or cyclophosphamide [3].
Immunodeficiency does not appear to predispose to atrophic papulosis, with no reports of co-occurrence with primary immunodeficiency disorders. However, an occurrence of nonprogressive atrophic papulosis in a patient with human immunodeficiency virus (HIV) has been reported [19]. There is also a report of an increase in characteristic skin lesions after kidney transplantation and immunosuppressive treatment in a patient with benign familial atrophic papulosis [20].
●Infection – Electron microscopic findings of paramyxovirus-like inclusion bodies in endothelial cells have been reported in atrophic papulosis [6,21]. Ribonucleic acid (RNA) transcripts have been identified for parvovirus B19 in a few patients [4].
●Thrombophilia – Thrombophilia might increase the risk of arterial and venous thrombosis in atrophic papulosis [22]. In an early report of three patients with atrophic papulosis, elevated levels of fibrinogen were found in two patients (one with skin-limited atrophic papulosis and the other with systemic involvement) [23]. Patchy perivascular fibrinogen deposition in the upper dermis was detected in the patient with skin-only disease.
EPIDEMIOLOGY —
Atrophic papulosis is a rare disorder with limited epidemiologic data. However, the diagnosis may be underrecognized due to the asymptomatic nature of skin-limited disease.
●Age – Atrophic papulosis appears to develop most often during adulthood, but the disease may also occur in children. In a prospective cohort study that assessed 39 patients with atrophic papulosis (ages 5 to 60 years) who were followed for at least five years, the average age of disease onset (onset of skin lesions) was approximately 35 years [17]. In a retrospective study that included 19 pediatric patients with atrophic papulosis, the median age of onset among the pediatric patients was 5 years [24]. Few cases have been reported in newborns [25,26].
●Sex – Some studies suggest an overall female predominance but with extracutaneous involvement occurring at a similar or greater frequency in males [17,24,27]. In a retrospective review of 65 published reports of patients with atrophic papulosis associated with gastrointestinal involvement, among the 63 patients for whom sex was reported, 46 percent were female and 54 percent were male [28].
In children, atrophic papulosis appears to occur more often in males than in females, and extracutaneous involvement appears to be more common than in adults [24]. (See 'Disease course' below.)
CLINICAL MANIFESTATIONS
Disease course — Although the hallmark of atrophic papulosis is the presence of pathognomonic skin lesions (picture 1B and picture 1A, 1C-D), the disease can affect multiple organ systems. The skin, gastrointestinal system, and central nervous system are the most common sites of involvement [27,29,30]. Patients may have multiorgan involvement [17].
Skin involvement is often (but not always) the initial sign of atrophic papulosis, and patients who subsequently develop systemic involvement often do so within the first few years after skin lesions appear.
●In a prospective cohort study of adults and children in whom skin findings were the initial manifestation of atrophic papulosis, 11 of 38 patients followed for at least five years (29 percent) had documentation of systemic involvement [17]. The median time to development of systemic manifestations after the appearance of skin lesions was one year (range zero to seven years).
●In a systematic review of published reports that identified 357 patients with atrophic papulosis, 228 had systemic involvement [30]. Cutaneous involvement preceding, following, occurring simultaneously, or not occurring was documented in 44, 14, 9, and 3 percent of the patients with systemic involvement. The average time to onset of systemic disease after skin disease was approximately 2 years (range 0 to 28 years).
●In a study that assessed registry data from 77 adults and 19 children diagnosed with atrophic papulosis, central nervous system, gastrointestinal, and cardiac involvement were more common among pediatric patients than adult patients (79 versus 53 percent) [24]. The time to onset of systemic involvement in pediatric patients ranged broadly from almost 3 years prior to skin involvement to 20 years after skin involvement.
Based on the systematic review findings described above, internal involvement without the eventual development of skin lesions appears to be infrequent [30].
Of note, the frequency of systemic manifestations may be overestimated. Many cases of asymptomatic, skin-limited involvement may go unrecognized, and systemic cases might be more likely to be published than skin-limited cases. (See "Systematic review and meta-analysis", section on 'Publication and reporting bias'.)
Manifestations
Skin — The pathognomic skin lesions are porcelain-white papules with erythematous telangiectatic borders (picture 1A and picture 1B-D). The distinctive telangiectatic border represents one of the most specific features of the skin lesions [14]. Hyperpigmentation may be present at the periphery of the skin lesions in patients with moderately to darkly pigmented skin [31,32].
The skin lesions first appear as erythematous papules and subsequently evolve to exhibit pathognomonic features. The lesions are usually nonpruritic and painless.
The number of lesions can range from a few lesions to hundreds. The trunk and extremities are the most common sites of involvement. Rarely, lesions occur on the palms, soles, or head.
Gastrointestinal tract — The intestines are considered the most frequently affected internal organs in atrophic papulosis [28]. Atrophic papulosis lesions have also been detected in other abdominal sites, such as the surface of the liver and peritoneum [33].
●Symptoms and complications – The most common symptom is abdominal pain that may be severe. Other symptoms can include loss of appetite, nausea, emesis, diarrhea, constipation, gastrointestinal bleeding, and/or weight loss [28].
Organ perforation can occur, and intestinal perforation is a leading cause of death from atrophic papulosis [29]. We consider patients with laparoscopic lesions characteristic of atrophic papulosis at high risk of perforation, even in the absence of abdominal pain, as the duration of pain before perforation can be brief. (See "Atrophic papulosis (Köhlmeier-Degos disease): Diagnosis and management", section on 'Laparoscopy'.)
The small intestine is the most common site of perforation. In a review of published reports that identified a total of 58 perforations in 32 patients with atrophic papulosis, 74 percent of perforations occurred in the small intestine [28]. Colonic, gastric, esophageal, and undocumented site perforations accounted for 19, 5, 1, and 10 percent of perforations, respectively. Intestinal perforation can recur in patients who survive this complication and in whom the disease is not successfully treated.
●Radiologic findings – Peritoneal enhancement and nodular omentum have been detected on abdominal computed tomography (CT) but are not specific for atrophic papulosis [34,35]. CT of the abdomen may also demonstrate sites of perforation in late disease.
Central nervous system — Central nervous system involvement is a common manifestation of systemic disease [27,29]. In one series, central nervous system involvement was present in 22 of 41 adults and 12 of 15 pediatric patients with evidence of systemic atrophic papulosis [24].
●Symptoms and complications – Central nervous system involvement often presents with headaches that can be severe. Examples of other manifestations include seizure disorders, occlusive or hemorrhagic strokes, cognitive impairment, central visual disturbances, and cranial nerve palsies [36,37].
●Radiologic findings – Radiologic findings are nonspecific. Magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) features may include [36,37]:
•Cortical, subcortical, and deep white matter infarcts
•Venous sinus thrombosis
•Stenosis or obstruction of the small and middle subarachnoid and extraparenchymal arteries
•Leptomeningeal and dural enhancement
•Subdural hematomas or hygromas
•Spinal cord lesions
●Cerebrospinal fluid – The cerebrospinal fluid usually reveals pleocytosis and an elevated protein level [38].
Other sites — Other recognized sites of involvement include the eyes, pleura, pericardium, urogenital system, and peripheral nervous system.
●Eyes – Avascular patches on the conjunctiva, including the bulbar conjunctiva, are the most common ocular manifestation [39]. The episclera, sclera, choroid, retina, and optic nerve can also become involved. Clinically, eye and central nervous system involvement can result in ophthalmoplegia (diplopia), visual field defects, ptosis, papilledema, and optic nerve atrophy [40,41].
●Pleura and pericardium – Pleural or pericardial effusions are common manifestations of cardiopulmonary involvement [42-44]. A unique constrictive fibrosing encasement of the pericardium and pleura has been described [14,42,44]. Fibrinous plaques can occur in the pleura, with fibrinoid necrotic change in the underlying arterioles [23].
●Urogenital system – Bladder wall lesions appear similar to those in bowel serosa and, in our experience, may present with microscopic or gross hematuria. Renal failure has also been reported [45].
●Peripheral nervous system – There are infrequent reports of peripheral nervous system findings such as polyradiculopathy and neuropathy [36].
HISTOPATHOLOGY
●Skin – Active lesions demonstrate a unique and stereotypical neointimal proliferative arteriopathy that can also involve the microvasculature, with relative sparing of the venous circulation [46,47]. In addition, there is significant extravascular connective tissue matrix deposition, specifically hyaluronic acid and collagen deposition.
•Early findings – The earliest erythematous papules demonstrate an endotheliopathy, often with an angiocentric lymphocytic infiltrate. Interstitial mucin is present, suggestive of enhanced hyaluronic acid production by dermal fibroblasts. Subtle endothelial cell injury can be observed along with mural fibrin deposition. This early stage of the disease has been compared with the pathology of the tumid variant of discoid lupus [14].
•Subsequent findings – Eventually, endothelial cell sloughing and thrombosis in the arteriolar lumen leads to loss of perfusion of the watershed area in the adjacent tissues. The blocked vessels do not seem to elicit either a lymphocytic infiltrate or neoangiogenesis. The vessel walls begin demonstrating a thickened and hyalinized appearance.
The depressed porcelain center of the skin lesions corresponds histologically to a hypovascular or avascular sclerosis process with an overlying hyperkeratotic scale. Intimal expansion ultimately leads to the stereotypical neointimal proliferative arteriopathy that is a hallmark of atrophic papulosis in the skin [14].
Late skin lesions acquire a morphologic resemblance to guttate variants of lichen sclerosus et atrophicus, with atrophic epidermal findings and subepidermal fibrosis with vascular drop out [14]. The findings are often described as wedge-shaped areas with epidermal atrophy and dermal sclerosis with loss of adnexal structures.
●Serosa – Biopsy of serosal lesions reveals an obliterative intimal arteriopathy with acellular deposits of mucin and collagen along with perivascular sclerosis. There is no significant evidence of inflammation or the destruction of the internal elastic lamina diagnostic of vasculitis.
In gastrointestinal lesions, the thrombotic microvascular changes characteristically observed in the capillaries and venules of affected skin are not present in the lamina propria. The vascular pathology involves only arterioles and is accompanied by extravascular sclerosis in the subserosal fat [28]. Immunofluorescence studies have shown C5b-9 deposition and myxovirus resistance protein A (MxA) staining reflective of an interferon-alpha gene expression signature in blood vessels of the involved tissue [28]. (See 'Pathogenesis' above.)
●Brain – The carotid and vertebrobasilar arteries often develop small fibrous subendothelial plaques, and there can be abundant fibrosis of the meninges with collagen accumulation in the cortical sulci and the subarachnoid spaces [38].
●Kidney – In a patient with renal involvement, the large- and medium-sized arteries in the kidneys showed sclerotic changes with no necrosis [23]. Special stains showed predominantly sclerotic and focal thrombotic changes at the periphery of fibrohyalinized regions [23]. Similar findings were reported in an adolescent who presented with acute kidney failure [45].
ASSOCIATED DISORDERS —
Atrophic papulosis-like lesions have been reported in patients with some rheumatic disorders [48]. Examples include patients with overlapping features of skin lesions of atrophic papulosis and either systemic lupus erythematosus or systemic sclerosis [49-52] and patients with dermatomyositis and atrophic papulosis-like systemic involvement [53-56].
PROGNOSIS —
Prior to the recognition of effective treatment options, many patients with systemic atrophic papulosis died within two to three years following the onset of extracutaneous manifestations [30].
Eculizumab and treprostinil are proposed to be life-saving interventions for patients with gastrointestinal involvement based on observations of rapid clinical improvement following the initiation of these therapies. (See "Atrophic papulosis (Köhlmeier-Degos disease): Diagnosis and management", section on 'Management'.)
Mortality in skin-limited versus systemic disease — In contrast to the generally favorable prognosis of skin-limited atrophic papulosis, systemic disease can lead to life-threatening complications when unsuccessfully treated [17,24,27].
●In a cohort of 38 patients with atrophic papulosis followed for 5 to 12 years between 2000 and 2012, 8 of 11 patients with systemic involvement died compared with none with skin-only involvement [17]. The mean survival time from the time of development of systemic disease was 0.9 years based on data available from nine patients. The cumulative five-year survival rate among patients with systemic disease was 54.5 percent.
●In a cohort study of patient data collected between 2000 and 2021 that included 19 patients with onset of atrophic papulosis during childhood (age 0 to 17 years), 15 had systemic involvement [24]. Six patients died, all of whom had systemic involvement. Among those who died, the median survival time from the development of systemic involvement to death was 15 months (range 1.7 months to 6 years).
Causes of death — Complications related to gastrointestinal or central nervous system involvement appear to be major contributors to death from atrophic papulosis [27]. (See 'Gastrointestinal tract' above and 'Central nervous system' above.)
●In a systematic review of published reports that identified 357 patients with atrophic papulosis, of the 129 patients for whom fatal outcomes were reported, the most common causes of death were gastrointestinal bleeding (23 percent), cachexia (19 percent), cardiac and/or pulmonary failure (16 percent), sepsis (13 percent), and cerebral infarction (7 percent) [30].
●In a review of published reports of atrophic papulosis with gastrointestinal involvement, of the 32 patients with documented gastrointestinal perforation, only five were alive at the time of case publication [28]. Sepsis or severe peritonitis was the cause of death in 19 patients.
●In a retrospective cohort study that documented six deaths in patients with pediatric-onset atrophic papulosis, three died of central nervous system complications, two died of gastrointestinal complications, and the cause of death was unknown for one patient [24].
●In a series of 15 patients with atrophic papulosis, including 10 with various neurologic manifestations, followed for 2 to 27 years (median 13 years), five patients had fatal hemorrhagic or ischemic strokes [57].
Pregnancy outcomes — Few cases of atrophic papulosis in pregnancy have been reported. Outcomes have included uncomplicated pregnancies and healthy infants, the development of skin lesions in a three-month-old infant without subsequent evidence for systemic involvement, and a full-term but lower birthweight infant [58-60]. In one patient with an uncomplicated pregnancy and healthy infant, pathologic examination of the placenta showed no abnormalities [60].
SUMMARY AND RECOMMENDATIONS
●Disease overview – Atrophic papulosis (also known as Köhlmeier-Degos disease) is a rare nonvasculitic vasculopathy that classically presents with characteristic skin lesions with or without associated systemic involvement. The exact pathogenesis is unknown. (See 'Terminology' above and 'Classification' above and 'Pathogenesis' above.)
●Epidemiology – Atrophic papulosis most frequently occurs in adults but may occur in infants and children. Compared with adults, systemic involvement may be more frequent in children. Systemic involvement may also be more common in males than in females. (See 'Epidemiology' above.)
●Clinical manifestations
•Skin – The characteristic skin lesions of atrophic papulosis are porcelain-white papules with an erythematous telangiectatic border (picture 1A-D). Many patients who present with skin-only involvement do not progress to systemic disease. (See 'Skin' above.)
•Systemic involvement – Systemic involvement most often follows the appearance of skin lesions. Less frequently, it may precede, occur concurrently, or occur independently of skin disease. The gastrointestinal system and central nervous system are the most common sites of systemic disease. Examples of other potential sites of involvement include the eyes, pleura, pericardium, and urogenital system. (See 'Gastrointestinal tract' above and 'Central nervous system' above and 'Other sites' above.)
●Prognosis – Atrophic papulosis is a potentially fatal disorder. However, mortality secondary to atrophic papulosis appears limited to patients with systemic disease. Death most often results from complications related to gastrointestinal or central nervous system disease. (See 'Prognosis' above.)
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