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Last updated: 8/7/2023
Years published: 1994, 1999, 2000, 2003, 2010, 2023
NORD gratefully acknowledges Katherine Bockholt and Elizabeth Caradonna, NORD Editorial Interns from the University of Notre Dame, Lee Shapiro, MD, Albany Medical College, and Patrick Whelan, MD, PhD, David Geffen School of Medicine, UCLA, for assistance in the preparation of this report.
Degos disease is an extremely rare disorder, with only about 200 reported cases worldwide. In affected individuals, arteries of smaller diameter become blocked (occlusive arteriopathy), subsequently restricting the flow of blood to affected areas. Degos disease usually presents with characteristic skin lesions (porcelain-white macules) that may persist for several weeks or even years. Degos disease can occur at any age, with onset of symptoms typically between the age of 20 and 50. In most individuals, the symptoms of Degos disease are limited to the skin, termed benign cutaneous Degos disease. This form of the disease has an excellent prognosis.
Other individuals will develop additional symptoms that affect multiple organ systems, in which the disease is then termed systemic Degos disease. Systemic Degos disease can develop suddenly or several years following the development of the benign cutaneous type. Degos disease has a potentially life-threatening prognosis: a 50% risk of death within 2-3 years of symptom emergence. In addition to dermal atrophy, systemic Degos disease is most frequently characterized by lesions in the small intestine, and, less often, other portions of the gastrointestinal tract. Some of these lesions may ultimately perforate. Major symptoms prior to perforation include abdominal pain, diarrhea and/or weight loss. This systemic form of Degos disease can lead to other disabling and potentially life-threatening complications if the central nervous system, heart, or lung are involved.
Researchers caution that statistics concerning Degos disease may be inaccurate. Because of its rarity, many affected individuals go undiagnosed. Furthermore, medical reports disproportionately discuss the more serious, systemic form of the disease. It is important to note that about two-thirds of all patients only develop non-life-threatening skin lesions. In addition, recent advances in drug therapy have dramatically improved the potential for recovery of even those severely afflicted by the systemic form of the disease. Most cases reported in the literature were published when no effective treatment option was available. Affected individuals should talk to their physicians and medical team about their specific case and associated symptoms.
In most people, the initial sign of Degos disease is the development of skin lesions which evolve to a very distinct appearance (see below). Affected individuals develop small, elevated bumps or spots (papules) of varying shapes, typically appearing on the trunk, upper arms and upper legs. At onset, only a few lesions may be present, but over time, the skin often continues to develop lesions, so that ultimately hundreds may appear. The palms of the hands, soles of the feet and face are usually not affected so that lesions may not be apparent to others. Over a period of weeks to months, the lesions typically transition from reddish or pink bumps to flat or depressed porcelain-white lesions with a red rim.
In some people, blood vessels of other organ systems are also affected (systemic Degos disease), resulting in serious and potentially life-threatening complications. Individuals who develop systemic Degos disease will not necessarily (and usually does not) develop all the symptoms discussed below.
The most common internal organ affected by systemic Degos disease is the gastrointestinal (GI) tract. Gastrointestinal involvement may present anywhere from a few weeks to a few years after the skin lesions develop. In extremely rare cases, gastrointestinal involvement may precede the development of skin lesions.
Due to the occlusion (blockage) of blood vessels and restricted blood flow present in Degos disease, lesions can form in the small intestines, resulting in abdominal pain, cramping, nausea, vomiting, diarrhea, bloating, constipation, internal bleeding (hemorrhage) and the passing of blood with bowel movements or vomiting blood. Some affected individuals may experience weakness, fatigue and weight loss from malabsorption of nutrients in the small intestine. The intestinal lesions can tear or rupture (perforate), causing the contents of the intestines to leak into the abdominal cavity (intestinal fistula). This results in inflammation of the membranes lining the abdominal cavity (peritonitis), which is a life-threatening complication and the most common cause of death in Degos patients.
Some individuals with systemic Degos disease experience involvement of the central nervous system (CNS). Symptoms of CNS involvement vary depending upon the specific areas affected but may include headaches, dizziness (vertigo), seizures, paralysis (palsy) of cranial nerves, weakness of one side of the body (hemiparesis), ischemic strokes and damage to small areas of cells in the brain due to blocked arteries (cerebral infarcts). Nonspecific neurological symptoms such as memory loss, difficulty communicating (aphasia), pain insensitivity and altered sensations may also occur. CNS involvement Degos disease nearly always indicates severe disease and poor prognosis.
In rare cases, additional organ systems that may become involved include the eyes, heart, lungs and bladder. When the eyes are affected, individuals may develop double vision (diplopia), drooping of the eyelids (ptosis), clouding of the lenses of the eyes (cataracts), atrophy of the optic nerve, swelling of the optic nerve (papilledema), partial loss of the field of vision (visual-field defects) and blindness caused by lack of blood flow to the eyes (amaurosis fugax).
When the heart is affected, individuals may develop weakness, shortness of breath upon exertion and chest pain. In some cases, inflammation of the sac-like membrane surrounding the heart (pericardium) may occur. This may develop into permanent thickening, resulting in scarring and contracture of the pericardium (constrictive pericarditis).
Inflammation of the membranes lining the lungs (pleuritis) and fluid collection around the lungs (pleural effusion) has also been reported. Respiratory failure can eventually occur.
Degos disease is caused by multiplication of the cells lining small arteries, resulting in the narrowing or blocking of affected vessels termed arterial occlusion. Areas of severely damaged tissue (necrosis) may appear in locations where these affected arteries restrict blood flow, known as occlusive arteriopathy. The symptoms and severity of Degos disease depend upon the location of the blocked arteries and necrotic lesions (characterized by cell death in tissues).
The underlying cause of this cellular multiplication remains unknown, though many theories have been proposed. These possibilities include viral infection, vasculitis (inflammation of the blood vessels), abnormal blood clotting (coagulopathy or a primary disorder of endothelial cells that line the blood vessels) or autoimmunity (whereby the bodyโs immune system mistakenly attacks healthy tissue).
Some cases of Degos disease are believed to be genetic and inherited and follow an autosomal dominant inheritance pattern. Other cases lack any perceived genetic cause. Interestingly, cases of Degos disease with a genetic component are usually limited to the skin (benign cutaneous Degos disease), thus typically giving a better prognosis. In one case a specific variant in a gene was identified which resulted in over-activity of the interferon receptor at cell surfaces.
The work of Dr. Cynthia Mago has provided evidence that Degos disease is, at least in part, a C5b-9 / interferon-ษ- mediated endothelial disease. Both C5b-9 and interferon-ษ (IFN-ษ) were found to have extensive expression in affected cutaneous (skin) tissues. Affected individuals have excessive deposits of C5b-9, the membranolytic attack complex, which can result in cell death in areas of attachment of the complex. IFN-ษ is an innate immune cytokine that manages viral replication rate and shapes immunological responses in the downstream C5b-9 response. It may be an important mechanism in fibrotic changes which can lead to occlusion of small blood vessels.
Further research is required to determine the true underlying cause of the disease.
Since its recognition as a distinct clinical entity by Dr. Degos in 1942, well more than 200 cases of Degos disease have been reported in the medical literature; however, the exact incidence of the disorder is unknown. Many researchers believe that Degos disease is under-diagnosed, making it difficult to determine its true frequency in the general population. Degos disease can affect individuals of any age, with one case reporting an onset as early as 8 months old; however, symptoms most frequently appear between the ages of 20-50. Males have been affected more often than females, with a male predominance of 3:1. One study found that females developed the benign cutaneous form of Degos disease more often than males.
Identification of the characteristic skin lesions is typically the first step in the diagnosis of Degos disease. Mature lesions have white centers and pink/red borders due to dilated blood vessels, and are primarily located on the chest, back and upper extremities. Biopsy of affected tissue reveals necrosis (tissue cell death due to lack of blood supply) and blockage of small arterioles. This microscopic examination of affected skin tissue reveals a wedge-shaped area of necrotic tissue, a distinctive change that is characteristic of Degos disease. No specific laboratory test can be used to aid in the diagnosis of Degos disease. Most lab tests return normal results, though anemia may manifest in certain individuals with the systemic form of the disease. Imaging (i.e., MRI, EEG, and EMG) may be used to identify affected areas of the brain and body with systemic Degos disease. Gastrointestinal lesions of Degos, when present, involve the outer (serosal) surface of the bowel, especially the small bowel. As with skin lesions, bowel lesions have a highly characteristic appearance and are best visualized by performance of laparoscopy (endoscopy and colonoscopy are much less sensitive methods to detect these lesions).
Treatment
Degos Disease should be suspected in any individual with the highly typical skin lesions and diagnosis should be confirmed by skin biopsy and review of the slides by an experienced dermatopathologist. The diagnosis by itself may provoke a great deal of anxiety. This is best addressed by rapid evaluation to exclude evidence of systemic disease. If evidence of systemic disease is detected, evaluation by an expert in Degos Disease is advised as treatment for systemic disease is in a rapid state of evolution. But we are well past the circumstance, described in so many papers in the literature, when diagnosis of systemic disease meant no effective intervention existed.
Many articles in medical literature suggest that anti-platelet therapy is warranted even in those with skin-only disease. Evidence of the benefit of this therapy is sparse. All individuals with skin-only disease should be educated as to signs that could signal development of systemic disease. Baseline laparoscopy is the most effective means of establishing or ruling out the presence of gastrointestinal Degos. There are currently no guidelines as to how often this should be repeated in subsequent years, but it certainly should be considered whenever persistent new gastrointestinal symptoms develop. Baseline chest x-ray, echocardiogram, EKG, ophthalmologic examination and brain MRI are also recommended.
The use of inhibitors of activation of C5, a complement component, has been lifesaving in multiple individuals with gastrointestinal Degos. Due to the extreme rarity of the disease, no double-blind placebo-controlled study of this therapy has been performed. However, when outcomes are compared to historical โcontrolsโ, the many articles in which death is the only outcome of those with gastrointestinal Degos, the change is remarkable (Sattler et al, 2022). The addition of treprostinil, a prostacyclin analogue, has been reported to provide more prolonged effect as compared to use of complement inhibition alone (Shapiro et al). Currently, anti-inteferon therapy is under study for those with Degos involving the central nervous system.
All too often individuals with systemic Degos are diagnosed only after catastrophic complications have occurred. Treatment always requires recognition of the disease, and the earlier recognition occurs, the more effective treatment interventions are likely to be in preventing irreversible organ damage or death.
Unfortunately, the approaches mentioned above involve the โoff-labelโ use of the medications described. This means they have not been approved by the U.S. Food and Drug Administration (FDA) specifically to treat Degos disease. These agents may be difficult or impossible to access. Delay involved in obtaining approval for drug administration can only negatively impact treatment outcomes. Intensive advocacy is often necessary. Every effort is being made to publish reports of drug efficacy in the medical literature so that access can become easier.
Some researchers have advocated for the use of intravenous immunoglobulin (IVIG) as a treatment for affected individuals. IVIG is a treatment technique in which plasma proteins from blood donors are administered via a drip directly into the patientโs bloodstream. This method can be used to treat autoimmune, infectious and idiopathic diseases. More research is necessary to determine the long-term safety and efficacy of such therapies in individuals with Degos disease, as results of this attempted treatment have been inconsistent.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Hollar C, Williford PL. Degos Disease. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:102.
JOURNAL ARTICLES
Pukhalskaya T, Stiegler J, Scott G, Richardson CT, Smoller B. Degos Disease (Malignant Atrophic Papulosis) With Granular IgM on Direct Immunofluorescence. Cureus. 2021;13(1):e12677. Published 2021 Jan 13. doi:10.7759/cureus.12677
Moran EJ, Lapin WB, Calame D, et al. Degos disease: A radiological-pathological correlation of the neuroradiological aspects of the disease. Ann Diagn Pathol. 2020;47:151545. doi:10.1016/j.anndiagpath.2020.151545
Tummidi, S, Nagendran P, Gedela S. et al. Degos disease: a case report and review of the literature. J Med Case Reports. 2020;14. https://doi.org/10.1186/s13256-020-02514-6
Saracino D, DโArmiento FP, Conforti R, et al. Dramatic neurological debut in a case of Kรถhlmeier-Degos disease. Neurol Sci. 2019;40(10):2201-2203. doi:10.1007/s10072-019-03952-x
Huang YC, Wang JD, Lee FY, Fu LS. Pediatric malignant atrophic papulosis. Pediatrics. 2018;141(Suppl 5):S481-S484. doi:10.1542/peds.2016-4206
Wang SC, Patel H, Shapiro LS, et al. KohlmeierโDegos disease with constrictive pericarditis and atrial fibrillation. J Echocardiogr. 2018;16: 192โ193. https://doi.org/10.1007/s12574-018-0386-4
Shapiro LS, Toledo-Garcia AE, Farrell JF. Effective treatment of malignant atrophic papulosis (Kรถhlmeier-Degos disease) with treprostinilโearly experience. Orphanet J Rare Dis. 2013;8:52. Published 2013 Apr 4. doi:10.1186/1750-1172-8-52
Magro C, Poe J, Kim C, Shapiro L, Nuovo G, Crow M and Crow Y. Degos Disease. American Journal of Clinical Pathology 2011; 135(4): pp.599-610.
Scheinfeld N. Malignant atrophic papulosis. Clin Exp Dermatol. 2007;32:483-487.
Zhu KJ, Zhou Q, Lin AH, Lu Zm, Cheng H. The use of intravenous immunoglobulin in cutaneous and recurrent perforating intestinal Degos disease (malignant atrophic papulosis). Br J Dermatol. 2007;57:206-207.
Zamiri M, Jarrett P, Snow J. Benign cutaneous Degos disease. Int J Dermatol. 2005;44:654-656.
Scheinfeld N. Degos disease is probably a distinct entity: a review of clinical and laboratory evidence. J Am Acad Dermatol. 2005;52:375-376.
Amato C, Ferri R, Elia M, et al. Nervous system involvement in Degos disease. AJNR Am J Neuroradiol. 2005;26:646-649.
Kocheril SV, Blaivas M, Appleton BE, McCune WJ, Ike RW. Degosโ disease mimicking vasculitis. Arthritis Rheum. 2004;51:498-500.
Kanekura T, Uchino Y, Kanzaki T. A case of malignant atrophic papulosis successfully treated with nicotine patches. Br J Dermatol. 2003;149:660-662.
Torrelo A, Sevilla J, Mediero IG, Candelas D, Zambrano A. Malignant atrophic papulosis in an infant. Br J Dermatol. 2002;146:916-918.
Harvell JD, Williford PL, White WL. Benign cutaneous Degosโ disease. A case report with emphasis on histopathology as papules chronologically evolve. Am J Dermatopathol. 2001;23:116-123.
Farrel AM, Moss J, Costello C, et al. Benign cutaneous Degosโ disease. Br J Dermatol. 1998;139:708-712.
INTERNET
Rice AS, Zedek D. Malignant Atrophic Papulosis. [Updated 2022 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544329/ Accessed August 7, 2023.
Scheinfeld N. Degos Disease (Kohlmeier Disease, Degos-Kohlmeier Disease, Malignant Atrophic Papulosis, Benign Atrophic Papulosis, Malignant atrophic papulosis, benign atrophic papulosis, Malignant atrophic papulosis). Dermatology Advisor. 2019. www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/degos-disease-kohlmeier-disease-degos-kohlmeier-disease-malignant-atrophic-papulosis-benign-atrophic-papulosis-malignant-atrophic-papulosis/ Accessed August 7, 2023.
Malignant Atrophic Papulosis. Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/6249/malignant-atrophic-papulosis Accessed August 7, 2023.
Scheinfeld N. Commentary on Degos Disease A C5b-9/Interferon-ฮฑ-Mediated Endotheliopathy Syndrome by Magro et al: A reconsideration of Degos Disease as hematologic or endothelial genetic disease. Dermatology Online Journal 2011; 17(8). https://escholarship.org/uc/item/09r396d1 Accessed August 7, 2023.
OโHarris M. Degos Disease. Medscape. Dec 10, 2019. Available at: https://www.emedicine.com/derm/topic931.htm Accessed August 7, 2023.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:602248; Last Update: 09/17/2012. Available at: https://www.omim.org/entry/602248 Accessed August 7, 2023.
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