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Degos disease: Considerations for reclassification
This month’s selected commentary
Degos disease: Considerations for reclassification Warren R. Heymann, MD Based on the dialogue ‘‘Degos disease’’ between Noah Scheinfeld, MD, and Stuart Brown, MD Dialogues in Dermatology, a monthly audio program from the American Academy of Dermatology, contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editor-inChief Warren R. Heymann, MD, are provided after each discussion as a topic summary and are provided here as a special service to readers of the Journal of the American Academy of Dermatology. ( J Am Acad Dermatol 2009;61:505-6.)
T
he recognition of a rose-colored papule that becomes umbilicated, healing with a porcelain white center with surrounding erythema and telangiectasias, allows the astute dermatologist to diagnose Degos disease (DD; also known as malignant atrophic papulosis) virtually instantaneously. That is the easy part. Attempting to ascertain the nature of this potentially fatal illness, determining its prognosis, and devising a therapeutic regimen for the patient is a daunting task. According to Lester and Rapini,1 DD ‘‘is a vasoocclusive disease of unknown cause involving small and medium-sized arteries affecting the skin, gastrointestinal tract, central nervous system (CNS), and less often other organ systems; it is quite rare, with about 200 cases reported in the literature. The mean age of onset is 35 years, men affected outnumber women 1.3 to 3 to 1, and familial cases suggesting autosomal dominant inheritance have been reported.’’ When systemic involvement occurs, it characteristically presents within months to years following the dermatologic manifestations. According to Wilson et al,2 the most common causes of death are sepsis from peritonitis (61%), CNS bleeding (18%), and pleural or pericardial involvement (16%). The authors note, however, that up to 15% of patients appear to have a benign course unaccompanied by any systemic disease. They reported the case of a 16-year-old female with characteristic lesions and an unremarkable workup for autoimmune or coagulation disorders who remained well with the administration of aspirin. She was followed up for 16 months. The authors reviewed the literature regarding the concept of benign cutaneous DD, The statements and opinions expressed in this commentary are those of the Editor-in-Chief of Dialogues in Dermatology.
identifying 34 patients (30 adults and 4 children) who had at least 1 year of follow-up. The average age was 37.6 years; however, this variant was more common in women by a 3 to 1 ratio. No laboratory studies allowed a prediction of a benign versus a malignant course. Because of the relatively short term followup, it is difficult to state emphatically that some patients may not have ultimately developed systemic disease, because this may happen up to 10 years after the development of cutaneous lesions.2 Histologically, lesions from patients with benign disease or those with systemic involvement are indistinguishable. According to Mydlarski et al,3 ‘‘Characteristic histologic findings include a wedgeshaped area of collagen degeneration, an interface reaction of squamatization of the dermal-epidermal junction, a developing zone of papillary dermal sclerosis, melanin incontinence, and epidermal atrophy. Early lesions have a perivascular, periadnexal, and perineural inflammatory infiltrate with initerstitial mucin deposition. Swelling and proliferation of endothelial cells and thrombosis may be seen beneath the zone of necrobiosis.’’ The etiology of DD is undetermined. The three main theories of the pathogenesis of DD include viral, autoimmune, or coagulation abnormalities. Degos-like lesions may occur in patients with antiphospholipid antibodies. In addition, increased circulating levels of fibrinogen and cryoprofibrin and increased platelet aggregation and adhesiveness have been reported.4 High et al5 presented four patients: one with classical DD, two with cutaneous lesions of DD but with laboratory evidence suggestive of lupus erythematosus (one of whom also had IgG antiphospholipid antibodies), and one with DD lesions and cutaneous features of dermatomyositis. The authors 505
506 Dialogues in Dermatology
J AM ACAD DERMATOL SEPTEMBER 2009
concluded that DD disease may not be a specific entity, but rather a ‘‘reaction pattern’’ as a common end point to a host of vascular insults, many of which are yet to be determined. Guhl et al6 presented a patient with Wegener granulomatosis who developed DD lesions during a flare of his disease. Dyrsen et al7 reported the case of a 38-year-old man who developed abdominal pain, followed by respiratory failure, localized DD-like lesions, and severe proximal polyneuropathy. His disorder was temporally associated with parvovirus B19 viremia; viral RNA transcripts were localized to the vascular endothelium. The patient showed significant improvement with the administration of intravenous immunoglobulin (IVIG).7 Unfortunately, despite anecdotal reports, there are no known routinely effective treatments for DD. Considerations for first-line treatments include heparin, coumadin, aspirin, and dipyridamole; secondline therapies include phenformin, ethylestrenol, nicotine patches, lansoprazole ( for gastrointestinal ulceration), and cyclosporine; third-line treatments include azathioprine, cyclophosphamide, tacrolimus, IVIG, and ultraviolet B light phototherapy.8 What should the clinician do when the patient presents with DD lesions? A history and physical examination focusing on gastrointestinal, neurologic, and cardiac disease, performing a skin biopsy, checking a complete blood count, autoimmune profile (ie, antinuclear antibodies and antineutrophilic cytoplasmic antibodies), coagulation studies (ie, anticardiolipin antibodies, protein C, protein S, factor V Leiden, antithrombin III, and homocysteine levels), and a parvovirus B19 titer are all appropriate. Although it is also essential to explain to the patient that it is not possible to prognosticate, cautious optimism should be provided, noting that patients who do not display systemic manifestations within a few years are likely to have benign disease. Shakespeare’s Juliet asked Romeo: What’s in a name? That which we call a rose By any other name would smell as sweet. —Romeo and Juliet (II, ii, 1-2). In dermatology, precise nomenclature is crucial because labels lead to diagnostic and/or therapeutic considerations. Perhaps we are approaching the time when we will be able to reclassify DD. Although there may be overlapping features of the subsets of any proposed subclassification, when more data is accrued, such stratification could help in prognostication or therapeutic intervention. After the previously described workup, patients could be
classified as having: (1) classical DD with systemic manifestations, further subclassified with either autoimmune DD (if there are associated clinical and/or laboratory features of either connective tissue disease or vasculitis), coagulopathy-associated DD, and virally-induced DD; or (2) benign cutaneous DD (assuming normal studies and a lack of systemic manifestations after 3 years). Until more research unravels the mysteries of this vasculopathy, any such categorization must be considered preliminary in the attempt to ultimately help guide clinicians in managing this potentially devastating disease. REFERENCES 1. Lester LU, Rapini RP. Dermatologic manifestations of colonic disorders. Curr Opin Gastroenterol 2009;25:66-73. 2. Wilson J, Walling HW, Stone MS. Benign cutaneous Degos disease in a 16-year-old girl. Pediatr Dermatol 2007;24:18-24. 3. Mydlarski PR, Barber DF, Robertson LH. Painless pink papules with central porcelain-white scars. CMAJ 2008;179:1171-3. 4. Weinstein S, Piette W. Cutaneous manifestations of antiphospholipid antibody syndrome. Hematol Oncol Clin North Am 2008;22:67-77. 5. High WA, Aranda J, Patel SB, Cockerell CJ, Costner MI. Is Degos’ disease a clinical and histological end point rather than a specific disease? J Am Acad Dermatol 2004;50:895-9. 6. Guhl G, Diaz-Ley B, Delgado Y, Daude´n E, Fraga J, Garcı´a-Diez A. Wegener’s granulomatosis: an new entity in the growing differential diagnosis of Degos’ disease. Clin Exp Dermatol 2008 Nov 24 [Epub ahead of print]. 7. Dyrsen ME, Iwenofu OH, Nuovo G, Magro CM. Parvovirus B19-associated catastrophic endothelialitis with Degos-like presentation. J Cutan Pathol 2008;35(suppl 1):20-5. 8. Scheinfeld N. Malignant atrophic papulosis (Degos disease). In: Lebwohl M, Heymann W, Berth-Jones J, Coulson I, Treatment of skin disease, 2nd ed. London: Mosby; 2005.
Additional topics from the August 2009 issue of the Dialogues in Dermatology: 1. Treatment of hyperhidrosis With Kevin C. Smith, MD, interviewed by Joel Barkoff, MD 2. Nail tips and tricks With Phoebe Rich, MD, interviewed by Stuart Brown, MD Dialogues in Dermatology is published monthly by the American Academy of Dermatology in both audio cassette and CD formats. Corporate and editorial offices: 930 E Woodfield Dr, Schaumburg, IL 60173-4729. 2009 subscription rates: $150 for individuals in the United States, Canada, and Mexico; $200 international. ª 2009 by the American Academy of Dermatology, Inc. Subscriptions are available by calling toll-free: (866) 503-7546 or faxing (847) 240-1859. Additional information is available in the Marketplace section of www.aad.org.
Degos disease: Considerations for reclassification Warren R. Heymann, MD Based on the dialogue ‘‘Degos disease’’ between Noah Scheinfeld, MD, and Stuart Brown, MD Dialogues in Dermatology, a monthly audio program from the American Academy of Dermatology, contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editor-inChief Warren R. Heymann, MD, are provided after each discussion as a topic summary and are provided here as a special service to readers of the Journal of the American Academy of Dermatology. ( J Am Acad Dermatol 2009;61:505-6.)
T
he recognition of a rose-colored papule that becomes umbilicated, healing with a porcelain white center with surrounding erythema and telangiectasias, allows the astute dermatologist to diagnose Degos disease (DD; also known as malignant atrophic papulosis) virtually instantaneously. That is the easy part. Attempting to ascertain the nature of this potentially fatal illness, determining its prognosis, and devising a therapeutic regimen for the patient is a daunting task. According to Lester and Rapini,1 DD ‘‘is a vasoocclusive disease of unknown cause involving small and medium-sized arteries affecting the skin, gastrointestinal tract, central nervous system (CNS), and less often other organ systems; it is quite rare, with about 200 cases reported in the literature. The mean age of onset is 35 years, men affected outnumber women 1.3 to 3 to 1, and familial cases suggesting autosomal dominant inheritance have been reported.’’ When systemic involvement occurs, it characteristically presents within months to years following the dermatologic manifestations. According to Wilson et al,2 the most common causes of death are sepsis from peritonitis (61%), CNS bleeding (18%), and pleural or pericardial involvement (16%). The authors note, however, that up to 15% of patients appear to have a benign course unaccompanied by any systemic disease. They reported the case of a 16-year-old female with characteristic lesions and an unremarkable workup for autoimmune or coagulation disorders who remained well with the administration of aspirin. She was followed up for 16 months. The authors reviewed the literature regarding the concept of benign cutaneous DD, The statements and opinions expressed in this commentary are those of the Editor-in-Chief of Dialogues in Dermatology.
identifying 34 patients (30 adults and 4 children) who had at least 1 year of follow-up. The average age was 37.6 years; however, this variant was more common in women by a 3 to 1 ratio. No laboratory studies allowed a prediction of a benign versus a malignant course. Because of the relatively short term followup, it is difficult to state emphatically that some patients may not have ultimately developed systemic disease, because this may happen up to 10 years after the development of cutaneous lesions.2 Histologically, lesions from patients with benign disease or those with systemic involvement are indistinguishable. According to Mydlarski et al,3 ‘‘Characteristic histologic findings include a wedgeshaped area of collagen degeneration, an interface reaction of squamatization of the dermal-epidermal junction, a developing zone of papillary dermal sclerosis, melanin incontinence, and epidermal atrophy. Early lesions have a perivascular, periadnexal, and perineural inflammatory infiltrate with initerstitial mucin deposition. Swelling and proliferation of endothelial cells and thrombosis may be seen beneath the zone of necrobiosis.’’ The etiology of DD is undetermined. The three main theories of the pathogenesis of DD include viral, autoimmune, or coagulation abnormalities. Degos-like lesions may occur in patients with antiphospholipid antibodies. In addition, increased circulating levels of fibrinogen and cryoprofibrin and increased platelet aggregation and adhesiveness have been reported.4 High et al5 presented four patients: one with classical DD, two with cutaneous lesions of DD but with laboratory evidence suggestive of lupus erythematosus (one of whom also had IgG antiphospholipid antibodies), and one with DD lesions and cutaneous features of dermatomyositis. The authors 505
506 Dialogues in Dermatology
J AM ACAD DERMATOL SEPTEMBER 2009
concluded that DD disease may not be a specific entity, but rather a ‘‘reaction pattern’’ as a common end point to a host of vascular insults, many of which are yet to be determined. Guhl et al6 presented a patient with Wegener granulomatosis who developed DD lesions during a flare of his disease. Dyrsen et al7 reported the case of a 38-year-old man who developed abdominal pain, followed by respiratory failure, localized DD-like lesions, and severe proximal polyneuropathy. His disorder was temporally associated with parvovirus B19 viremia; viral RNA transcripts were localized to the vascular endothelium. The patient showed significant improvement with the administration of intravenous immunoglobulin (IVIG).7 Unfortunately, despite anecdotal reports, there are no known routinely effective treatments for DD. Considerations for first-line treatments include heparin, coumadin, aspirin, and dipyridamole; secondline therapies include phenformin, ethylestrenol, nicotine patches, lansoprazole ( for gastrointestinal ulceration), and cyclosporine; third-line treatments include azathioprine, cyclophosphamide, tacrolimus, IVIG, and ultraviolet B light phototherapy.8 What should the clinician do when the patient presents with DD lesions? A history and physical examination focusing on gastrointestinal, neurologic, and cardiac disease, performing a skin biopsy, checking a complete blood count, autoimmune profile (ie, antinuclear antibodies and antineutrophilic cytoplasmic antibodies), coagulation studies (ie, anticardiolipin antibodies, protein C, protein S, factor V Leiden, antithrombin III, and homocysteine levels), and a parvovirus B19 titer are all appropriate. Although it is also essential to explain to the patient that it is not possible to prognosticate, cautious optimism should be provided, noting that patients who do not display systemic manifestations within a few years are likely to have benign disease. Shakespeare’s Juliet asked Romeo: What’s in a name? That which we call a rose By any other name would smell as sweet. —Romeo and Juliet (II, ii, 1-2). In dermatology, precise nomenclature is crucial because labels lead to diagnostic and/or therapeutic considerations. Perhaps we are approaching the time when we will be able to reclassify DD. Although there may be overlapping features of the subsets of any proposed subclassification, when more data is accrued, such stratification could help in prognostication or therapeutic intervention. After the previously described workup, patients could be
classified as having: (1) classical DD with systemic manifestations, further subclassified with either autoimmune DD (if there are associated clinical and/or laboratory features of either connective tissue disease or vasculitis), coagulopathy-associated DD, and virally-induced DD; or (2) benign cutaneous DD (assuming normal studies and a lack of systemic manifestations after 3 years). Until more research unravels the mysteries of this vasculopathy, any such categorization must be considered preliminary in the attempt to ultimately help guide clinicians in managing this potentially devastating disease. REFERENCES 1. Lester LU, Rapini RP. Dermatologic manifestations of colonic disorders. Curr Opin Gastroenterol 2009;25:66-73. 2. Wilson J, Walling HW, Stone MS. Benign cutaneous Degos disease in a 16-year-old girl. Pediatr Dermatol 2007;24:18-24. 3. Mydlarski PR, Barber DF, Robertson LH. Painless pink papules with central porcelain-white scars. CMAJ 2008;179:1171-3. 4. Weinstein S, Piette W. Cutaneous manifestations of antiphospholipid antibody syndrome. Hematol Oncol Clin North Am 2008;22:67-77. 5. High WA, Aranda J, Patel SB, Cockerell CJ, Costner MI. Is Degos’ disease a clinical and histological end point rather than a specific disease? J Am Acad Dermatol 2004;50:895-9. 6. Guhl G, Diaz-Ley B, Delgado Y, Daude´n E, Fraga J, Garcı´a-Diez A. Wegener’s granulomatosis: an new entity in the growing differential diagnosis of Degos’ disease. Clin Exp Dermatol 2008 Nov 24 [Epub ahead of print]. 7. Dyrsen ME, Iwenofu OH, Nuovo G, Magro CM. Parvovirus B19-associated catastrophic endothelialitis with Degos-like presentation. J Cutan Pathol 2008;35(suppl 1):20-5. 8. Scheinfeld N. Malignant atrophic papulosis (Degos disease). In: Lebwohl M, Heymann W, Berth-Jones J, Coulson I, Treatment of skin disease, 2nd ed. London: Mosby; 2005.
Additional topics from the August 2009 issue of the Dialogues in Dermatology: 1. Treatment of hyperhidrosis With Kevin C. Smith, MD, interviewed by Joel Barkoff, MD 2. Nail tips and tricks With Phoebe Rich, MD, interviewed by Stuart Brown, MD Dialogues in Dermatology is published monthly by the American Academy of Dermatology in both audio cassette and CD formats. Corporate and editorial offices: 930 E Woodfield Dr, Schaumburg, IL 60173-4729. 2009 subscription rates: $150 for individuals in the United States, Canada, and Mexico; $200 international. ª 2009 by the American Academy of Dermatology, Inc. Subscriptions are available by calling toll-free: (866) 503-7546 or faxing (847) 240-1859. Additional information is available in the Marketplace section of www.aad.org.