XML Template (2014) [9.10.2014–9:15am] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/STDJ/Vol00000/140171/APPFile/SG-STDJ140171.3d
(STD)
[1–3] [PREPRINTER stage]
Int J STD AIDS OnlineFirst, published on October 13, 2014 as doi:10.1177/0956462414553013
Case report
A rare case of immune reconstitution inflammatory syndrome presenting as secondary syphilis
International Journal of STD & AIDS 0(0) 1–3 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414553013 std.sagepub.com
Asma Khatri1,2 and Marion J Skalweit1,3
Summary Immune reconstitution syndrome has rarely been reported in the context of syphilis infection. We report a patient with AIDS (CD4 42 cells/mm3, viral load 344,000 cp/ml), treated previously for secondary syphilis and started on an integrase inhibitor-based single-tablet antiretroviral treatment regimen. After four weeks of antiretroviral treatment, he presented with non-tender, non-blanching erythematous nodules on his chest, an elevated rapid plasma reagin (1:1024) and immune reconstitution (CD4 154 cells/mm3, HIV-RNA 130 cp/ml). A detailed workup to exclude opportunistic infections including secondary and neurosyphilis was performed. The patient was continued on antiretroviral treatment and treated empirically for neurosyphilis given cerebrospinal lymphocytosis and dermatopathology suggesting treponemal antigendriven B-cell hyperplasia. We favour a diagnosis of immune reconstitution in association with prior syphilis infection attributable to rapid and potent immune restoration afforded by integrase inhibitors.
Keywords Human immunodeficiency virus, AIDS, immune reconstitution syndrome, IRIS, syphilis, HIV integrase inhibitors Date received: 30 July 2014; accepted: 1 September 2014
Introduction Immune reconstitution inflammatory syndrome (IRIS) occurs in HIVþ patients who begin antiretroviral therapy (ART). IRIS is a response to an undiagnosed or quiescent opportunistic infection (OI) and is often selflimited, improving with continuation of ART alone. IRIS is most associated with OIs involving Mycobacterium avium, Mycobacterium tuberculosis and Cryptococcus neoformans. Here, we report an unusual presentation of a man with presumptive secondary syphilis and IRIS.
Case report A 43-year-old man who has sex with men (MSM) presented in February 2014 to our outpatient clinic to establish HIV primary care. He was HIVþ since 1994, previously on ART including nucleoside reverse-transcriptase inhibitors, non-nucleoside reverse-transcriptase inhibitors and HIV protease inhibitors but was not adherent. He suffered numerous OIs: two episodes of Pneumocystis jiroveci pneumonia in 2002; M. avium bacteremia in 2003; M. avium, Klebsiella pnemoniae and Hemophilus influenzae
pneumonia in 2010; and secondary syphilis (2005, 2012) treated with benzathine penicillin G, 2 million units IM qweek 3 doses. At presentation to our clinic, he had been off ART for one year but continued his OI prophylaxis (dapsone daily, azithromycin weekly). His CD4 count was 42 cells/mm3 (5%), HIVRNA 344,000 cp/ml and rapid plasma reagin (RPR) 1:16. No prior HIV genotype was available, and genotype testing off ART revealed a fully susceptible virus; to improve adherence, once daily tenofovir/emtricitabine/cobicistat/elvitegravir-(StribildTM)1 was initiated. Four weeks later, he presented with non-blanching, non-tender erythematous papules limited to the chest 1 Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA 2 Department of Medicine, Case Medical Center, Cleveland, OH, USA 3 Case Western Reserve University School of Medicine, Cleveland, OH, USA
Corresponding author: Marion J Skalweit, Infectious Diseases Section, Department of Veterans Affairs Medical Center, Louis Stokes Cleveland, 111(W), 10701 East Blvd., Cleveland, OH 44106, USA. Email: [email protected]
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(STD)
[1–3] [PREPRINTER stage]
2
International Journal of STD & AIDS 0(0)
Figure 1. (a) Non-tender, non-blanching erythematous papules limited to the chest at initial presentation and (b) Papules after two weeks of IV penicillin therapy.
(Figure 1(a)). Patient denied travel, animal exposures or sexual encounters including oral, vaginal or anal intercourse in the past six months. Review of systems and examination revealed no findings other than rash. Blood count showed mild pancytopenia. Liver and renal laboratory values and urinalysis were normal. RPR was 1:1024. CD4 was 154 cells/mm3 (6%), and HIV-RNA was 130 cp/ml. C-reactive protein was 1.1 mg/dl (range 0–1). Cerebrospinal fluid (CSF) analysis revealed 54 RBCs and 26 WBCs (86% lymphocytes) with normal protein and glucose. Blood and CSF fungal and bacterial antigens, bacterial, mycobacterial and viral cultures and polymerase chain reaction (PCR) studies for herpes simplex 1&2 were negative. CSF venereal disease research laboratory was negative. Cutaneous biopsy showed dense dermal lymphoplasmacytic and histiocytic inflammation. Treponema pallidum immunostain was negative for organisms, but given the poor immunostain sensitivity, a diagnosis of syphilis could not be excluded. Furthermore, dermatologic assessment suggested IRIS versus secondary syphilis-driven B-cell hyperplasia, less likely B-cell lymphoma.2 The patient was continued on his ART and was treated presumptively for neurosyphilis. Repeat RPR was 1:256, CD4 209 cells/mm3 (6%) and HIV RNA was
(STD)
[1–3] [PREPRINTER stage]
Int J STD AIDS OnlineFirst, published on October 13, 2014 as doi:10.1177/0956462414553013
Case report
A rare case of immune reconstitution inflammatory syndrome presenting as secondary syphilis
International Journal of STD & AIDS 0(0) 1–3 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414553013 std.sagepub.com
Asma Khatri1,2 and Marion J Skalweit1,3
Summary Immune reconstitution syndrome has rarely been reported in the context of syphilis infection. We report a patient with AIDS (CD4 42 cells/mm3, viral load 344,000 cp/ml), treated previously for secondary syphilis and started on an integrase inhibitor-based single-tablet antiretroviral treatment regimen. After four weeks of antiretroviral treatment, he presented with non-tender, non-blanching erythematous nodules on his chest, an elevated rapid plasma reagin (1:1024) and immune reconstitution (CD4 154 cells/mm3, HIV-RNA 130 cp/ml). A detailed workup to exclude opportunistic infections including secondary and neurosyphilis was performed. The patient was continued on antiretroviral treatment and treated empirically for neurosyphilis given cerebrospinal lymphocytosis and dermatopathology suggesting treponemal antigendriven B-cell hyperplasia. We favour a diagnosis of immune reconstitution in association with prior syphilis infection attributable to rapid and potent immune restoration afforded by integrase inhibitors.
Keywords Human immunodeficiency virus, AIDS, immune reconstitution syndrome, IRIS, syphilis, HIV integrase inhibitors Date received: 30 July 2014; accepted: 1 September 2014
Introduction Immune reconstitution inflammatory syndrome (IRIS) occurs in HIVþ patients who begin antiretroviral therapy (ART). IRIS is a response to an undiagnosed or quiescent opportunistic infection (OI) and is often selflimited, improving with continuation of ART alone. IRIS is most associated with OIs involving Mycobacterium avium, Mycobacterium tuberculosis and Cryptococcus neoformans. Here, we report an unusual presentation of a man with presumptive secondary syphilis and IRIS.
Case report A 43-year-old man who has sex with men (MSM) presented in February 2014 to our outpatient clinic to establish HIV primary care. He was HIVþ since 1994, previously on ART including nucleoside reverse-transcriptase inhibitors, non-nucleoside reverse-transcriptase inhibitors and HIV protease inhibitors but was not adherent. He suffered numerous OIs: two episodes of Pneumocystis jiroveci pneumonia in 2002; M. avium bacteremia in 2003; M. avium, Klebsiella pnemoniae and Hemophilus influenzae
pneumonia in 2010; and secondary syphilis (2005, 2012) treated with benzathine penicillin G, 2 million units IM qweek 3 doses. At presentation to our clinic, he had been off ART for one year but continued his OI prophylaxis (dapsone daily, azithromycin weekly). His CD4 count was 42 cells/mm3 (5%), HIVRNA 344,000 cp/ml and rapid plasma reagin (RPR) 1:16. No prior HIV genotype was available, and genotype testing off ART revealed a fully susceptible virus; to improve adherence, once daily tenofovir/emtricitabine/cobicistat/elvitegravir-(StribildTM)1 was initiated. Four weeks later, he presented with non-blanching, non-tender erythematous papules limited to the chest 1 Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA 2 Department of Medicine, Case Medical Center, Cleveland, OH, USA 3 Case Western Reserve University School of Medicine, Cleveland, OH, USA
Corresponding author: Marion J Skalweit, Infectious Diseases Section, Department of Veterans Affairs Medical Center, Louis Stokes Cleveland, 111(W), 10701 East Blvd., Cleveland, OH 44106, USA. Email: [email protected]
Downloaded from std.sagepub.com at UCSF LIBRARY & CKM on January 28, 2015
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(STD)
[1–3] [PREPRINTER stage]
2
International Journal of STD & AIDS 0(0)
Figure 1. (a) Non-tender, non-blanching erythematous papules limited to the chest at initial presentation and (b) Papules after two weeks of IV penicillin therapy.
(Figure 1(a)). Patient denied travel, animal exposures or sexual encounters including oral, vaginal or anal intercourse in the past six months. Review of systems and examination revealed no findings other than rash. Blood count showed mild pancytopenia. Liver and renal laboratory values and urinalysis were normal. RPR was 1:1024. CD4 was 154 cells/mm3 (6%), and HIV-RNA was 130 cp/ml. C-reactive protein was 1.1 mg/dl (range 0–1). Cerebrospinal fluid (CSF) analysis revealed 54 RBCs and 26 WBCs (86% lymphocytes) with normal protein and glucose. Blood and CSF fungal and bacterial antigens, bacterial, mycobacterial and viral cultures and polymerase chain reaction (PCR) studies for herpes simplex 1&2 were negative. CSF venereal disease research laboratory was negative. Cutaneous biopsy showed dense dermal lymphoplasmacytic and histiocytic inflammation. Treponema pallidum immunostain was negative for organisms, but given the poor immunostain sensitivity, a diagnosis of syphilis could not be excluded. Furthermore, dermatologic assessment suggested IRIS versus secondary syphilis-driven B-cell hyperplasia, less likely B-cell lymphoma.2 The patient was continued on his ART and was treated presumptively for neurosyphilis. Repeat RPR was 1:256, CD4 209 cells/mm3 (6%) and HIV RNA was
