Concurrence of erythema elevatum diutinum and HIV infection: A case report and literature review
2019; Elsevier BV; Volume: 5; Issue: 12 Linguagem: Inglês
10.1016/j.jdcr.2019.10.011
ISSN2352-5126
AutoresSamuel W. Logan, Richard D. Sontheimer,
Tópico(s)Skin Diseases and Diabetes
ResumoA 55-year-old man with a history of HIV, first diagnosed in 2002, presented to our clinic in the spring of 2019 for evaluation of painful nodules on his feet and ankles bilaterally that were present for 7 months. Before the appearance of these lesions, he was untreated for his HIV for 10 months because of lack of follow-up with medical care. At the onset of symptoms, his CD4 count was 287 cells/μL. He resumed treatment for his HIV with bictegravir, emtricitabine, and tenofovir alafenamide combined tablet. At the time of our visit, his CD4 had increased to 452; however, he reported the lesions remained unchanged. On examination, violaceous, moderately firm, easily movable papules and nodules were present on his feet bilaterally with the largest over his left heel (Fig 1). A punch biopsy was performed, which showed mixed inflammatory perivascular infiltrate with neutrophilic predominance and fibrinoid material within vessel walls and surrounding fibrotic dermis (Fig 2). Based on these findings, erythema elevatum diutinum (EED) was diagnosed. Treatment with oral dapsone is planned.Fig 2Punch biopsy of EED lesion in adult male with history of HIV infection shows moderately dense dermal perivascular infiltrate composed primarily of neutrophils, nuclear dust, and macrophages with lymphocytes and eosinophils to a lesser degree. Fibrinoid material present in some vessels. Fibrotic surrounding dermis. (Hematoxylin-eosin stain; original magnification: ×20.)Photograph courtesy of Scott Florell, MD.View Large Image Figure ViewerDownload Hi-res image Download (PPT) EED is a rare chronic cutaneous small-vessel leukocytoclastic vasculitis that presents initially as soft, nonfixed red/violaceous or brown papules and nodules that later become firm because of fibrosis. The lesions are distributed most frequently on extensor surfaces of the hands, arms, and legs.1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar,2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar Involvement of the feet and plantar surface (as with our patient) is considered unusual and may represent as few as 4.2% of EED cases.2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar Its presentation may mimic that of Kaposi sarcoma, bacillary angiomatosis, granuloma annulare, and Sweet syndrome among others, and as such, histologic correlation is necessary for diagnosis.1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar Histologically, early lesions may resemble small vessel leukocytoclastic vasculitis from other causes with perivascular inflammation and leukocytoclastic debris within the papillary and mid dermis. As lesions progress to late stage, there is greater involvement of histiocytes and dermal spindle cells leading to fibrosis of lesions that may resemble sclerosing hemangioma.1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar The pathophysiology of this condition is likely caused by immune complex deposition in small vessels leading to an inflammatory cascade.1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar,2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar Dapsone is currently the treatment of choice; however, other therapies have been used including colchicine, intralesional and topical steroids, chloroquine, and surgical intervention.3Cardis M.A. Sowash M.G. Mosojane K.I. Kovarik C. HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.Dermatol Online J. 2018; 24Google Scholar In their review of the 86 cases published between 1977 and 2012, Momen et al1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar found EED to be associated with many other disease processes including HIV (n = 19/86 [22%]), IgA gammopathy, bacterial infection, and inflammatory bowel disease among others.1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar More recently, Doktor et al,2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar in their 2019 review of 133 cases of EED between 1990 and 2014, found 21 cases associated with HIV. Here we review the above case as well as the 32 electronically indexed cases of HIV-associated EED with reported CD4 counts that were published between 1986 and 2018. A search of PubMed, Google Scholar, and the University of Vermont's Online Library search system literature in June 2019 found 32 reported cases of the concurrence of EED and HIV infection with published CD4 counts (Table I). The remainder of this report focuses on an analysis addressing clinical issues relating to a possible association between these 2 clinical phenomena.Table IReview of published cases of EED occurring in association with HIV infectionSexAgeCD4 (cells/μL)This ReportM55287Cardis et al, 20183Cardis M.A. Sowash M.G. Mosojane K.I. Kovarik C. HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.Dermatol Online J. 2018; 24Google ScholarM24536Shi et al, 20184Shi K.Y. Vandergriff T. Late-stage nodular erythema elevatum diutinum mimicking sclerotic fibroma.J Cutan Pathol. 2018; 45: 94-96Google ScholarF60UnreportedVictoria-Martinez et al, 20165Victoria-Martinez A.N.A.M. Cubells-Sanchez L. Martinez-Leborans L. Sanchez-Carazo J.L. A man with HIV and papules and nodules on the knees.Clev Clin J Med. 2016; 83: 641Google ScholarM39528Jose et al, 20166Jose S.K. Marfatia Y.S. Erythema elevatum diutinum in acquired immune deficiency syndrome: can it be an immune reconstitution inflammatory syndrome?.Indian J Sex Transmit Dis. 2016; 37: 81Google ScholarM47204Rao et al, 20147Rao G.R. Joshi R. Prasad A.K.P. Amareswar A. Sandhya S. Sridevi M. Nodular erythema elevatum diutinum mimicking Kaposi's sarcoma in a human immunodeficiency virus infected patient.Indian J Dermatol. 2014; 59: 592Crossref PubMed Scopus (5) Google ScholarF52164Al Abadie et al, 20128Al Abadie M. Tariq A. Frankiewicz J. Treatment of erythema elevatum diutinum (EED) in HIV-positive Afro-Caribbean patient.J Am Acad Dermatol. 2012; 66: AB134Google ScholarM4870Maksimovic et al, 20109Maksimovic L. Duriez P. Lascaux-Cametz A.S. et al.Erythema elevatum diutinum associated with pyoderma gangrenosum in an HIV-positive patient.Ann de dermatologie de venereologie. 2010; 137: 386-390Google ScholarM53384Braun-Falco et al, 200710Braun-Falco M. Hofmann H. An HIV-positive man with slowly enlarging nodules on the extremities.Clin Infect Dis. 2007; 44: 976Google ScholarM23185Kim et al, 200311Kim H. Erythema elevatum diutinum in an HIV-positive patient.J Drugs Dermatol. 2003; 2: 411-412Google ScholarM53618Martín et al, 200112Martín J.I. Dronda F. Chaves F. Erythema elevatum diutinum, a clinical entity to be considered in patients infected with HIV-1.Clin Exp Dermatol. 2001; 26: 725-726Crossref PubMed Scopus (17) Google ScholarM27114Fakheri et al, 200113Fakheri A. Gupta S.M. White S.M. Don P.C. Weinberg J.M. Erythema elevatum diutinum in a patient with human immunodeficiency virus.Cutis. 2001; 68 (55): 41-42Google ScholarM51150Muratori et al, 199914Muratori S. Carrera C. Gorani A. Alessi E. Erythema elevatum diutinum and HIV infection: a report of five cases.Br J Dermatol. 1999; 141: 335-338Crossref PubMed Scopus (53) Google Scholar∗Case series.F29114M20332F44305M41742M34378Suarez et al, 199815Suarez J. Miguelez M. Villalba R. Nodular erythema elevatum diutinum in an HIV-1 infected woman: response to dapsone and antiretroviral therapy.Br J Dermatol. 1998; 138: 717-718Crossref PubMed Scopus (24) Google ScholarF37158Revenga et al, 199716Revenga F. Vera A. Munoz A. Liana F. Alejo M. Rodriguez-Peralto J. Erythema elevatum diutinum and AIDS: are they related?.Clin Exp Dermatol. 1997; 22: 250-251Crossref PubMed Scopus (17) Google ScholarM33102Dronda et al, 199617Dronda F. González-López A. Lecona M. Barros C. Erythema elevatum diutinum in human immunodeficiency virus-infected patients–report of a case and review of the literature.Clin Exp Dermatol. 1996; 21: 222-225Crossref PubMed Scopus (41) Google ScholarM32128C. Bachmeyer et al, 199618Bachmeyer C. Aractingi S. Erythema elevatum diutinum with HIV-2 infection.Lancet. 1996; 347: 1041-1042Abstract PubMed Scopus (12) Google ScholarM58112LeBoit et al, 199319LeBoit P. Cockerell C. Nodular lesions of erythema elevatum diutinum in patients infected with the human immunodeficiency virus.J Am Acad Dermatol. 1993; 28: 919-922Abstract Full Text PDF PubMed Scopus (55) Google Scholar∗Case series.M27168M37UnreportedM24146M32UnreportedRequena et al, 199120Requena L. Sanchez-Yus E. Martin L. et al.Erythema Elevatum Diutinum in a patient with acquired immunodeficiency syndrome: another clinical simulator of Kaposi's Sarcoma.Arch Dermatol. 1991; 127: 1819-1822Crossref PubMed Scopus (50) Google ScholarM33314Momen et al, 20141Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar and Doktor et al, 20192Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar†Review of 7 cases with unreported CD4 count.6M, 1F36.8 (Mean)Unreported∗ Case series.† Review of 7 cases with unreported CD4 count. Open table in a new tab The age of patients in Table I ranged between 20 and 60 with a mean of 38.51. Non-HIV–associated EED most commonly presents between the fourth and sixth decade of life.1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar However, there may be an earlier age of onset in patients with HIV,3Cardis M.A. Sowash M.G. Mosojane K.I. Kovarik C. HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.Dermatol Online J. 2018; 24Google Scholar a finding that fits with the data in Table I. A male sex predominance was noted with 81.8% (27 of 33) of patients in Table I. Men make up 55.6% of all cases of EED2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar; however, the findings of this review are consistent with prior findings of HIV-associated EED.1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar, 2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar, 3Cardis M.A. Sowash M.G. Mosojane K.I. Kovarik C. HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.Dermatol Online J. 2018; 24Google Scholar This finding may reflect male/female population disparities with HIV as opposed to a true tendency toward men with HIV. Many reports associated EED in the setting of HIV with a CD4 count of less than 200.3Cardis M.A. Sowash M.G. Mosojane K.I. Kovarik C. HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.Dermatol Online J. 2018; 24Google Scholar,13Fakheri A. Gupta S.M. White S.M. Don P.C. Weinberg J.M. Erythema elevatum diutinum in a patient with human immunodeficiency virus.Cutis. 2001; 68 (55): 41-42Google Scholar,20Requena L. Sanchez-Yus E. Martin L. et al.Erythema Elevatum Diutinum in a patient with acquired immunodeficiency syndrome: another clinical simulator of Kaposi's Sarcoma.Arch Dermatol. 1991; 127: 1819-1822Crossref PubMed Scopus (50) Google Scholar However, our review of the reported data and our case does not support this finding. The mean CD4 count of EED cases in Table I (in which CD4 counts were reported) was 266.41, 50% (11 of 22) of cases being associated with CD4 counts higher than 200. This finding is complicated by the fact that only 66.7% (22 of 33) HIV-associated EED cases reported CD4 counts. These findings indicate that more data are needed from a more cases before a clinically significant association between CD4 counts and EED can be established. We encourage further reports on EED in the setting of HIV that include CD4 counts whenever possible. Until more such data are available, it may be more appropriate to consider a CD4 count of less than 300 to be a risk factor for EED in patients with HIV. Dapsone was the most common treatment in 75.6% (24 of 33) of the EED/HIV cases in Table II. Of these, 70.8% (17 of 24) were able to achieve complete or partial remission with the remainder either experiencing adverse events, failing to respond, or having unknown results. Of note, one patient achieved complete remission with combination topical dapsone and intralesional corticosteroids following oral corticosteroids.5Victoria-Martinez A.N.A.M. Cubells-Sanchez L. Martinez-Leborans L. Sanchez-Carazo J.L. A man with HIV and papules and nodules on the knees.Clev Clin J Med. 2016; 83: 641Google Scholar Topical therapy may represent a treatment option following nonhypersensitivity adverse effects to oral dapsone.Table IIReview of treatment outcomes of HIV-associated EEDTreatmentComplete remissionPartial remissionAdverse eventFailedUnknownTotalDapsone1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar, 2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar, 3Cardis M.A. Sowash M.G. Mosojane K.I. Kovarik C. HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.Dermatol Online J. 2018; 24Google Scholar,5Victoria-Martinez A.N.A.M. Cubells-Sanchez L. Martinez-Leborans L. Sanchez-Carazo J.L. A man with HIV and papules and nodules on the knees.Clev Clin J Med. 2016; 83: 641Google Scholar, 6Jose S.K. Marfatia Y.S. Erythema elevatum diutinum in acquired immune deficiency syndrome: can it be an immune reconstitution inflammatory syndrome?.Indian J Sex Transmit Dis. 2016; 37: 81Google Scholar, 7Rao G.R. Joshi R. Prasad A.K.P. Amareswar A. Sandhya S. Sridevi M. Nodular erythema elevatum diutinum mimicking Kaposi's sarcoma in a human immunodeficiency virus infected patient.Indian J Dermatol. 2014; 59: 592Crossref PubMed Scopus (5) Google Scholar, 8Al Abadie M. Tariq A. Frankiewicz J. Treatment of erythema elevatum diutinum (EED) in HIV-positive Afro-Caribbean patient.J Am Acad Dermatol. 2012; 66: AB134Google Scholar, 9Maksimovic L. Duriez P. Lascaux-Cametz A.S. et al.Erythema elevatum diutinum associated with pyoderma gangrenosum in an HIV-positive patient.Ann de dermatologie de venereologie. 2010; 137: 386-390Google Scholar, 10Braun-Falco M. Hofmann H. An HIV-positive man with slowly enlarging nodules on the extremities.Clin Infect Dis. 2007; 44: 976Google Scholar,12Martín J.I. Dronda F. Chaves F. Erythema elevatum diutinum, a clinical entity to be considered in patients infected with HIV-1.Clin Exp Dermatol. 2001; 26: 725-726Crossref PubMed Scopus (17) Google Scholar, 13Fakheri A. Gupta S.M. White S.M. Don P.C. Weinberg J.M. Erythema elevatum diutinum in a patient with human immunodeficiency virus.Cutis. 2001; 68 (55): 41-42Google Scholar, 14Muratori S. Carrera C. Gorani A. Alessi E. Erythema elevatum diutinum and HIV infection: a report of five cases.Br J Dermatol. 1999; 141: 335-338Crossref PubMed Scopus (53) Google Scholar, 15Suarez J. Miguelez M. Villalba R. Nodular erythema elevatum diutinum in an HIV-1 infected woman: response to dapsone and antiretroviral therapy.Br J Dermatol. 1998; 138: 717-718Crossref PubMed Scopus (24) Google Scholar, 16Revenga F. Vera A. Munoz A. Liana F. Alejo M. Rodriguez-Peralto J. Erythema elevatum diutinum and AIDS: are they related?.Clin Exp Dermatol. 1997; 22: 250-251Crossref PubMed Scopus (17) Google Scholar, 17Dronda F. González-López A. Lecona M. Barros C. Erythema elevatum diutinum in human immunodeficiency virus-infected patients–report of a case and review of the literature.Clin Exp Dermatol. 1996; 21: 222-225Crossref PubMed Scopus (41) Google Scholar, 18Bachmeyer C. Aractingi S. Erythema elevatum diutinum with HIV-2 infection.Lancet. 1996; 347: 1041-1042Abstract PubMed Scopus (12) Google Scholar, 19LeBoit P. Cockerell C. Nodular lesions of erythema elevatum diutinum in patients infected with the human immunodeficiency virus.J Am Acad Dermatol. 1993; 28: 919-922Abstract Full Text PDF PubMed Scopus (55) Google Scholar, 20Requena L. Sanchez-Yus E. Martin L. et al.Erythema Elevatum Diutinum in a patient with acquired immunodeficiency syndrome: another clinical simulator of Kaposi's Sarcoma.Arch Dermatol. 1991; 127: 1819-1822Crossref PubMed Scopus (50) Google Scholar10544225Surgical excision14Muratori S. Carrera C. Gorani A. Alessi E. Erythema elevatum diutinum and HIV infection: a report of five cases.Br J Dermatol. 1999; 141: 335-338Crossref PubMed Scopus (53) Google Scholar,19LeBoit P. Cockerell C. Nodular lesions of erythema elevatum diutinum in patients infected with the human immunodeficiency virus.J Am Acad Dermatol. 1993; 28: 919-922Abstract Full Text PDF PubMed Scopus (55) Google Scholar300216Colchicine1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar,2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar,8Al Abadie M. Tariq A. Frankiewicz J. Treatment of erythema elevatum diutinum (EED) in HIV-positive Afro-Caribbean patient.J Am Acad Dermatol. 2012; 66: AB134Google Scholar120003Corticosteroids (systemic, intralesional, and topical)2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar,5Victoria-Martinez A.N.A.M. Cubells-Sanchez L. Martinez-Leborans L. Sanchez-Carazo J.L. A man with HIV and papules and nodules on the knees.Clev Clin J Med. 2016; 83: 641Google Scholar,12Martín J.I. Dronda F. Chaves F. Erythema elevatum diutinum, a clinical entity to be considered in patients infected with HIV-1.Clin Exp Dermatol. 2001; 26: 725-726Crossref PubMed Scopus (17) Google Scholar110204Antibiotics1Momen S. Jorizzo J. Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment.J Eur Acad Dermatol Venereol. 2014; 28: 1594-1602Crossref PubMed Scopus (67) Google Scholar,2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar,10Braun-Falco M. Hofmann H. An HIV-positive man with slowly enlarging nodules on the extremities.Clin Infect Dis. 2007; 44: 976Google Scholar,14Muratori S. Carrera C. Gorani A. Alessi E. Erythema elevatum diutinum and HIV infection: a report of five cases.Br J Dermatol. 1999; 141: 335-338Crossref PubMed Scopus (53) Google Scholar310509Pegylated interferon10Braun-Falco M. Hofmann H. An HIV-positive man with slowly enlarging nodules on the extremities.Clin Infect Dis. 2007; 44: 976Google Scholar000101Soft tissue radiotherapy10Braun-Falco M. Hofmann H. An HIV-positive man with slowly enlarging nodules on the extremities.Clin Infect Dis. 2007; 44: 976Google Scholar010001 Open table in a new tab Other reported treatments included colchicine, corticosteroids (oral, topical, and intralesional), surgical excision and antibiotics (fusidic acid, erythromycin, tetracycline, clarithromycin, and penicillin), pegylated interferon, and soft tissue radiotherapy. Three cases utilized colchicine as treatment, all of which achieved partial or complete remission. Corticosteroids in any preparation, when successful, were used in combination with other treatments. Surgical excision was performed in 18.2% (6 of 33) cases, with 50% (3 of 6) achieving complete resolution, although one of these patients was also treated with dapsone.14Muratori S. Carrera C. Gorani A. Alessi E. Erythema elevatum diutinum and HIV infection: a report of five cases.Br J Dermatol. 1999; 141: 335-338Crossref PubMed Scopus (53) Google Scholar Surgical excision may be appropriate in the setting of late-stage, fibrotic lesions.19LeBoit P. Cockerell C. Nodular lesions of erythema elevatum diutinum in patients infected with the human immunodeficiency virus.J Am Acad Dermatol. 1993; 28: 919-922Abstract Full Text PDF PubMed Scopus (55) Google Scholar However, of the 10 late-stage lesions treated with dapsone with known response, 5 completely or partially resolved, 3 discontinued dapsone because of adverse events, and 2 did not respond to treatment.3Cardis M.A. Sowash M.G. Mosojane K.I. Kovarik C. HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.Dermatol Online J. 2018; 24Google Scholar,5Victoria-Martinez A.N.A.M. Cubells-Sanchez L. Martinez-Leborans L. Sanchez-Carazo J.L. A man with HIV and papules and nodules on the knees.Clev Clin J Med. 2016; 83: 641Google Scholar, 6Jose S.K. Marfatia Y.S. Erythema elevatum diutinum in acquired immune deficiency syndrome: can it be an immune reconstitution inflammatory syndrome?.Indian J Sex Transmit Dis. 2016; 37: 81Google Scholar, 7Rao G.R. Joshi R. Prasad A.K.P. Amareswar A. Sandhya S. Sridevi M. Nodular erythema elevatum diutinum mimicking Kaposi's sarcoma in a human immunodeficiency virus infected patient.Indian J Dermatol. 2014; 59: 592Crossref PubMed Scopus (5) Google Scholar,9Maksimovic L. Duriez P. Lascaux-Cametz A.S. et al.Erythema elevatum diutinum associated with pyoderma gangrenosum in an HIV-positive patient.Ann de dermatologie de venereologie. 2010; 137: 386-390Google Scholar,10Braun-Falco M. Hofmann H. An HIV-positive man with slowly enlarging nodules on the extremities.Clin Infect Dis. 2007; 44: 976Google Scholar,14Muratori S. Carrera C. Gorani A. Alessi E. Erythema elevatum diutinum and HIV infection: a report of five cases.Br J Dermatol. 1999; 141: 335-338Crossref PubMed Scopus (53) Google Scholar,16Revenga F. Vera A. Munoz A. Liana F. Alejo M. Rodriguez-Peralto J. Erythema elevatum diutinum and AIDS: are they related?.Clin Exp Dermatol. 1997; 22: 250-251Crossref PubMed Scopus (17) Google Scholar,19LeBoit P. Cockerell C. Nodular lesions of erythema elevatum diutinum in patients infected with the human immunodeficiency virus.J Am Acad Dermatol. 1993; 28: 919-922Abstract Full Text PDF PubMed Scopus (55) Google Scholar,20Requena L. Sanchez-Yus E. Martin L. et al.Erythema Elevatum Diutinum in a patient with acquired immunodeficiency syndrome: another clinical simulator of Kaposi's Sarcoma.Arch Dermatol. 1991; 127: 1819-1822Crossref PubMed Scopus (50) Google Scholar This finding may indicate that surgical excision (or other therapy) is more appropriate after treatment failure with dapsone. Although use of dapsone was efficacious, it is limited by adverse events. Topical dapsone, colchicine, and surgical excision may warrant further study as rescue therapy following dapsone or even monotherapy. Doktor et al,2Doktor V. Hadi A. Hadi A. Phelps R. Goodheart H. Erythema elevatum diutinum: a case report and review of literature.Int J Dermatol. 2019; 58: 408-415Crossref PubMed Scopus (30) Google Scholar in their 2019 review of reported cases of EED, found 15.8% (21 of 133) of cases of HIV-associated EED. With the additional cases detailed in this report added to that number, HIV-associated EED may represent as much as 22.8% (33 of 145) of published cases. The prominence of HIV-associated EED in the literature is striking; however, it is possible that this is overreported compared with isolated EED, EED with mild presentation, or factors that may incline practitioners to not publish cases. EED in the setting of HIV may represent an immune reconstitution inflammatory syndrome6Jose S.K. Marfatia Y.S. Erythema elevatum diutinum in acquired immune deficiency syndrome: can it be an immune reconstitution inflammatory syndrome?.Indian J Sex Transmit Dis. 2016; 37: 81Google Scholar in which symptoms of infectious or inflammatory conditions worsen after initiation of antiretroviral therapy. In many reports in this review (including this report), patients were either untreated3Cardis M.A. Sowash M.G. Mosojane K.I. Kovarik C. HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.Dermatol Online J. 2018; 24Google Scholar,5Victoria-Martinez A.N.A.M. Cubells-Sanchez L. Martinez-Leborans L. Sanchez-Carazo J.L. A man with HIV and papules and nodules on the knees.Clev Clin J Med. 2016; 83: 641Google Scholar,15Suarez J. Miguelez M. Villalba R. Nodular erythema elevatum diutinum in an HIV-1 infected woman: response to dapsone and antiretroviral therapy.Br J Dermatol. 1998; 138: 717-718Crossref PubMed Scopus (24) Google Scholar or on unchanged maintenance treatment at onset of EED symptoms. This finding does not represent a clear pattern of increased prominence of symptoms related to starting antiretroviral therapy. Many reports did not discuss the course of therapy for HIV, making it difficult to fully support or refute immune reconstitution inflammatory syndrome as a component of this condition. The association between HIV and EED remains to be confidently characterized. When compared with all cases of EED, EED occurring in HIV might have a greater male predominance and a younger age of onset. Accordingly, patients presenting with EED, particularly younger male patients, may warrant screening for HIV as a possible comorbidity. Based on our analysis of the published literature, a CD4 count of less than 300 may represent a more appropriate risk factor for the development of EED in HIV patients than the prior suggestion of CD4 less than 200. However, the validity of this suggestion is limited by the small number of cases (22 of 33). Dapsone was the most commonly used treatment option for EED in HIV patients and completely or partially treated both early and late stage lesions. Other therapies, including topical dapsone, colchicine, topical clobetasol/fusidic acid combination therapy, and surgical excision may warrant consideration as alternate treatment options. Further reports of EED occurring in the context of HIV infection could better refine the relationship between HIV infection and this rare form of chronic cutaneous small-vessel leukocytoclastic vasculitis.
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