Letters to Editor Diseases. 5 th ed. Philadelphia: Churchill Livingstone; 2000. p. 2474‑90. 3. Kar HH. Incidence of secondary syphilis on a rise and need for a separate flow chart for its syndromic management. Indian J Sex Trans Dis 2004;25:22‑5. 4. Chapel TA. The variability of syphilitic chancres. Sex Transm Dis 1978;5:68‑70. 5. Koranne RV, Raju PJ. Atypical manifestation of early syphilis. Indian J Dermatol Venereol Leprol 1990;56:37‑9.
Dermatological manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome in era of highly active antiretroviral therapy Sir, Dermatological manifestations are seen at every stage of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS), and are often earliest and the only sign of HIV/AIDS. The advent of highly active antiretroviral therapy (HAART) has been largely beneficial to patients with HIV associated skin disease, but novel side effects of these drugs have emerged. [1,2] Thus, we had conducted cross sectional observational study to know the epidemiological profile of cutaneous manifestations of HIV in patients who were on HAART. This study was conducted in Dermatology Outpatient Department of SMIMER, Surat, from April 2010 to January 2011, with prior permission from institutional ethical committee. 150 HIV positive patients who were referred from antiretroviral therapy (ART) center and were on HAART were included in the study. Children below age of 18 years, pregnant women and patients with transient nevirapine induced rash were excluded from the study. Detailed history of selected patients was recorded in a predesigned proforma. Cases were thoroughly examined and investigated. Out of 150 cases, 107 (71.33%) were males and 43 (28.66%) were females. Majority of the patients
Access this article online Quick Response Code:
Website: www.ijstd.org
DOI: 10.4103/0253-7184.132410
were from age group of 31–40 years comprising 76 (50.66%) cases, followed by 41 (27.33%) in age group of 18–30 years, 25 (16.66%) in 41–50 years, and 8 (5.33%) cases were above the age of 51 years. Maximum number of cases observed were of adverse cutaneous drug eruption (ACDE) comprising 31 cases (20.66%), followed by herpes zoster (HZ) 22 (14.66%), dermatophytosis 19 (12.66%), papular and pruritic eruption (PPE) of HIV 18 (12.00%), herpes genitalis 15 (10%), pyoderma 12 (8%) and variable prevalence of other dermatosis. Broadly out of total patients, nearly 63.34% of patients were of infectious etiology, 20.66% were of drug reactions and 16.66% were of inflammatory conditions. This finding is corroborated with study done by Calista et al.[1] ACDE was the most common findings [Table 1] (20.66%) and was consistent with study done by Calista et al. [1] Their study also had reported 20% prevalence of ACDE in patients who were on HAART. Sharma et al. in their study have reported 44.4% ACDE in patients on HAART. [3] Out of 31; 29 patients had maculopapular rash, one patient had fixed drug reaction and one patient had Stevens–Johnson syndrome. In our study, 94 patients who were on nevirapine, 20 patients (21.27%) had experienced exanthematous rash. This finding was consistent with study done by Ward et al. [2] Sharma et al. reported nevirapine rash to the tune of 11.8%.[4] Second most common presentation was HZ (14.66%). This finding is corroborated with study done by Hengge et al.[5] Two patients had 2nd attack of HZ; two had multidermatomal HZ [Figure 1], three had HZ ophathalmicus (HZO). CD4+ count in two patients with 2nd attack of HZ was 226 cells/μmm and 436 cells/μmm. On other hand in patients with HZO median CD4+ count was 90 cells/μmm, suggesting advanced degree of immunosuppression. Dermatophytosis was next manifestation that had accounted for 12.66%, and is comparable to study done by Hengge et al. [5] Median CD4 count was
Indian Journal of Sexually Transmitted Diseases and AIDS 2014; Vol. 35, No. 1
73
Letters to Editor
Table 1: Cutaneous manifestation of HIV/AIDS Cutaneous manifestations ACDE HZ Dermatophytosis PPE Herpes genatalis Pyoderma Seborrheic dermatitis Herpes simplex (oral) Condylomata acuminata Molluscum contagiosum Onychomycosis Perineal herpes simplex Oral candidiasis Scabies Verruca vulgaris Mixed STD Pigmentation of nail
Our study on HAART (%) 20.66 14.66 12.66 12.00 10.00 08.00 04.66 04.00 03.33 02.66 02.66 02.00 02.00 02.00 02.00 01.33 01.33
Hengge et al. on HAART (%) (5) 03.50 04.01 13.20 25.50 12.30 13.50 17.60 ‑ 15.50 08.50 ‑ ‑ 20.20 02.30 14.10 ‑ ‑
Figure 1: Herpes zoster involving ophthalmic and maxillary division of trigeminal nerve
HIV=Human immunodeficiency virus; AIDS=Acquired immunodeficiency syndrome; HAART=Highly active antiretroviral therapy; ACDE=Adverse cutaneous drug eruption; HZ=Herpes zoster; PPE=Papular and pruritic eruption; STD=Sexually transmitted disease
230 cells/μmm; suggesting the early stage of HIV infection. PPE remains the most common noninfectious cutaneous manifestation in HIV. PPE and eosinophilic folliculitis may be the part of same spectrum of disease and this can complicate the interpretation of published studies. In our study we have restricted the use of terminology to PPE only and were accounted in 12% of cases which is comparable to study done by Calista et al.[1] Median CD4 count was 179 cells/μmm; this lower CD4+ count suggests the advanced stage of HIV disease. Herpes genitalis excluding the case of perineal herpes simplex; was present in 10.00% cases; is comparable to other studies. [5] Median CD4 count was 198 cells/μmm, suggestive of moderate degree of immunosuppression. All the three cases of perineal herpes simplex were presented with itching and burning sensation over scrotum without any typical history of vesicles formation and pain [Figure 2]. Thus this atypical presentation should be kept in mind to diagnose the case of perineal herpes simplex. Median CD4 count in perineal herpes simplex was 178 cells/μmm; lower than the cases of herpes genitalis.
Figure 2: Herpes simplex involving scrotum
corroborated with study done by Rodger and Leslie[6] and Maurer. [7] Most of the cases presented with furuncle with its typical presentation. Median CD4 count was 174 cells/μmm. It seems that there is reduction in opportunistic infections, infective dermatosis and malignancy after advent of HAART. HZ in particular is immune reconstitution inflammatory syndrome related and PPE remains on higher side. Variety of ACDE is an emerging challenge with more number of cases recently on ART. Sanjay S. Bosamiya, Jignesh B. Vaishnani, Anjum M. Momin
Department of Dermatology, Surat Municipal Institute of Medical Education and Research (SMIMER), Umarwada, Surat, Gujarat, India Address for correspondence: Dr. Sanjay S. Bosamiya, Department of Dermatology, Surat Municipal Institute of Medical
Bacterial infection was another common finding that had accounted for 8.00% cases; and this finding is 74
Education and Research, Umarwada, Surat ‑ 395 010 Gujarat, India. Email: [email protected]
Indian Journal of Sexually Transmitted Diseases and AIDS 2014; Vol. 35, No. 1
Letters to Editor
REFERENCES 1.
Calista D, Morri M, Stagno A, Boschini A. Changing morbidity of cutaneous diseases in patients with HIV after the introduction of highly active antiretroviral therapy including a protease inhibitor. Am J Clin Dermatol 2002;3:59‑62. 2. Ward HA, Russo GG, Shrum J. Cutaneous manifestations of antiretroviral therapy. J Am Acad Dermatol 2002;46: 284‑93. 3. Sharma A, Vora R, Modi M, Sharma A, Marfatia Y. Adverse effects of antiretroviral treatment. Indian J Dermatol Venereol Leprol 2008;74:234‑7. 4. Sharma A, Modi M, Sharma A, Marfatia YS. Cutaneous eruptions associated with nevirapine therapy in AIDS cases. Indian J Sex Transm Dis AIDS 2007;28:94‑6. 5. Hengge UR, Franz B, Goos M. Decline of infectious skin
Sinecatechins: A better prospect for treating anogenital warts Sir, Anogenital warts are the skin tumours caused by human papilloma virus (HPV) that may bother both the patients and their partners. Current treatment options are not satisfactory due to low efficacy and high recurrence rates. Although prophylactic vaccines have been recommended for adolescent women, more effective treatment modalities for anogenital warts are still needed. Topical Sinecatechins Ointment 15% is the first FDA approved botanical drug for treating anogenital warts.[1] Sinecatechins are a standardized extract of green tea leaves from Camellia sinensis, a species of the Theaceae family, containing polyphenols; particularly catechins (more than 85%). It contains eight different catechins and other green tea components. The main catechin in sinecatechins ointment his epigallocatechin gallate (EGCG), which has the highest biological activity.[2] Catechins exert multiple biologic activities by inhibiting a number of proteins, including enzymes involved in oxidative stress, blocking the kinases needed in tumour cell signalling and induction of apoptosis. These postulated mechanisms presumably contribute to the therapeutic effect of sinecatechins ointment. The proposed mechanisms of action of sinecatechins are:
Anti‑oxidant activity
The direct action of catechins is scavenging the reactive oxygen free radicals. Catechins may exert
manifestations in the era of highly active antiretroviral therapy. AIDS 2000;14:1069‑70. 6. Rodgers S, Leslie KS. Skin infections in HIV‑infected individuals in the era of HAART. Curr Opin Infect Dis 2011;24:124‑9.6. 7. Maurer TA. Dermatologic manifestations of HIV infection. Top HIV Med 2005;13:149‑54.7. Access this article online Quick Response Code:
Website: www.ijstd.org
DOI: 10.4103/0253-7184.132412
indirect antioxidant activity via inhibitory effects on transcription factors (e.g., nuclear factor‑κB [NF‑κB], activator protein‑1 [AP‑1]) and also inhibits the enzymes with activity that increases oxidative stress (e.g., lipoxygenases, cycloxygenases, and inducible nitric oxide). [3] EGCG also induces expression of endogenous antioxidant systems.
Anti‑proliferative activity
HPV E6 (early gene E6) degrades p53 (a tumour suppressor gene), inhibits the pro‑apoptotic protein BAK, activates telomerase and stabilizes Src‑family kinases. HPV E7 (early gene E7) inactivates Rb (a tumour suppressor gene). Conventionally, the Rb inhibits cell proliferation by binding to the E2F transcription factor (which controls the G1/S phase checkpoint of the cell cycle). Degradation of Rb by HPV E7 can result in uncontrolled cell division. A normal cell would react to this excessive cell division by p53‑dependent apoptosis; but the presence of HPV E6 prevents apoptosis by deactivation of p53 and BAK. The end result of their combined action (E6, E7) is cellular proliferation.[4] Catechins check the proliferation of cells by inhibiting kinases (receptor tyrosine kinases, telomerase) and promoting apoptosis.
Immuno‑stimulatory activity
HPV evades the immune system by reducing the expression of viral proteins in the immunogenic lower epithelial layers and decreased production of interferons. Catechins increase the activation of macrophages, lymphocytes, Langerhans cells and induction of cytokines (IL‑1β, TNF‑α, IFN‑γ), thereby eliciting cell‑mediated immunity against HPV. To conclude, not only has the sinecatechins had a wide spectrum of action but also the low recurrence
Indian Journal of Sexually Transmitted Diseases and AIDS 2014; Vol. 35, No. 1
75
Copyright of Indian Journal of Sexually Transmitted Diseases is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Dermatological manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome in era of highly active antiretroviral therapy Sir, Dermatological manifestations are seen at every stage of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS), and are often earliest and the only sign of HIV/AIDS. The advent of highly active antiretroviral therapy (HAART) has been largely beneficial to patients with HIV associated skin disease, but novel side effects of these drugs have emerged. [1,2] Thus, we had conducted cross sectional observational study to know the epidemiological profile of cutaneous manifestations of HIV in patients who were on HAART. This study was conducted in Dermatology Outpatient Department of SMIMER, Surat, from April 2010 to January 2011, with prior permission from institutional ethical committee. 150 HIV positive patients who were referred from antiretroviral therapy (ART) center and were on HAART were included in the study. Children below age of 18 years, pregnant women and patients with transient nevirapine induced rash were excluded from the study. Detailed history of selected patients was recorded in a predesigned proforma. Cases were thoroughly examined and investigated. Out of 150 cases, 107 (71.33%) were males and 43 (28.66%) were females. Majority of the patients
Access this article online Quick Response Code:
Website: www.ijstd.org
DOI: 10.4103/0253-7184.132410
were from age group of 31–40 years comprising 76 (50.66%) cases, followed by 41 (27.33%) in age group of 18–30 years, 25 (16.66%) in 41–50 years, and 8 (5.33%) cases were above the age of 51 years. Maximum number of cases observed were of adverse cutaneous drug eruption (ACDE) comprising 31 cases (20.66%), followed by herpes zoster (HZ) 22 (14.66%), dermatophytosis 19 (12.66%), papular and pruritic eruption (PPE) of HIV 18 (12.00%), herpes genitalis 15 (10%), pyoderma 12 (8%) and variable prevalence of other dermatosis. Broadly out of total patients, nearly 63.34% of patients were of infectious etiology, 20.66% were of drug reactions and 16.66% were of inflammatory conditions. This finding is corroborated with study done by Calista et al.[1] ACDE was the most common findings [Table 1] (20.66%) and was consistent with study done by Calista et al. [1] Their study also had reported 20% prevalence of ACDE in patients who were on HAART. Sharma et al. in their study have reported 44.4% ACDE in patients on HAART. [3] Out of 31; 29 patients had maculopapular rash, one patient had fixed drug reaction and one patient had Stevens–Johnson syndrome. In our study, 94 patients who were on nevirapine, 20 patients (21.27%) had experienced exanthematous rash. This finding was consistent with study done by Ward et al. [2] Sharma et al. reported nevirapine rash to the tune of 11.8%.[4] Second most common presentation was HZ (14.66%). This finding is corroborated with study done by Hengge et al.[5] Two patients had 2nd attack of HZ; two had multidermatomal HZ [Figure 1], three had HZ ophathalmicus (HZO). CD4+ count in two patients with 2nd attack of HZ was 226 cells/μmm and 436 cells/μmm. On other hand in patients with HZO median CD4+ count was 90 cells/μmm, suggesting advanced degree of immunosuppression. Dermatophytosis was next manifestation that had accounted for 12.66%, and is comparable to study done by Hengge et al. [5] Median CD4 count was
Indian Journal of Sexually Transmitted Diseases and AIDS 2014; Vol. 35, No. 1
73
Letters to Editor
Table 1: Cutaneous manifestation of HIV/AIDS Cutaneous manifestations ACDE HZ Dermatophytosis PPE Herpes genatalis Pyoderma Seborrheic dermatitis Herpes simplex (oral) Condylomata acuminata Molluscum contagiosum Onychomycosis Perineal herpes simplex Oral candidiasis Scabies Verruca vulgaris Mixed STD Pigmentation of nail
Our study on HAART (%) 20.66 14.66 12.66 12.00 10.00 08.00 04.66 04.00 03.33 02.66 02.66 02.00 02.00 02.00 02.00 01.33 01.33
Hengge et al. on HAART (%) (5) 03.50 04.01 13.20 25.50 12.30 13.50 17.60 ‑ 15.50 08.50 ‑ ‑ 20.20 02.30 14.10 ‑ ‑
Figure 1: Herpes zoster involving ophthalmic and maxillary division of trigeminal nerve
HIV=Human immunodeficiency virus; AIDS=Acquired immunodeficiency syndrome; HAART=Highly active antiretroviral therapy; ACDE=Adverse cutaneous drug eruption; HZ=Herpes zoster; PPE=Papular and pruritic eruption; STD=Sexually transmitted disease
230 cells/μmm; suggesting the early stage of HIV infection. PPE remains the most common noninfectious cutaneous manifestation in HIV. PPE and eosinophilic folliculitis may be the part of same spectrum of disease and this can complicate the interpretation of published studies. In our study we have restricted the use of terminology to PPE only and were accounted in 12% of cases which is comparable to study done by Calista et al.[1] Median CD4 count was 179 cells/μmm; this lower CD4+ count suggests the advanced stage of HIV disease. Herpes genitalis excluding the case of perineal herpes simplex; was present in 10.00% cases; is comparable to other studies. [5] Median CD4 count was 198 cells/μmm, suggestive of moderate degree of immunosuppression. All the three cases of perineal herpes simplex were presented with itching and burning sensation over scrotum without any typical history of vesicles formation and pain [Figure 2]. Thus this atypical presentation should be kept in mind to diagnose the case of perineal herpes simplex. Median CD4 count in perineal herpes simplex was 178 cells/μmm; lower than the cases of herpes genitalis.
Figure 2: Herpes simplex involving scrotum
corroborated with study done by Rodger and Leslie[6] and Maurer. [7] Most of the cases presented with furuncle with its typical presentation. Median CD4 count was 174 cells/μmm. It seems that there is reduction in opportunistic infections, infective dermatosis and malignancy after advent of HAART. HZ in particular is immune reconstitution inflammatory syndrome related and PPE remains on higher side. Variety of ACDE is an emerging challenge with more number of cases recently on ART. Sanjay S. Bosamiya, Jignesh B. Vaishnani, Anjum M. Momin
Department of Dermatology, Surat Municipal Institute of Medical Education and Research (SMIMER), Umarwada, Surat, Gujarat, India Address for correspondence: Dr. Sanjay S. Bosamiya, Department of Dermatology, Surat Municipal Institute of Medical
Bacterial infection was another common finding that had accounted for 8.00% cases; and this finding is 74
Education and Research, Umarwada, Surat ‑ 395 010 Gujarat, India. Email: [email protected]
Indian Journal of Sexually Transmitted Diseases and AIDS 2014; Vol. 35, No. 1
Letters to Editor
REFERENCES 1.
Calista D, Morri M, Stagno A, Boschini A. Changing morbidity of cutaneous diseases in patients with HIV after the introduction of highly active antiretroviral therapy including a protease inhibitor. Am J Clin Dermatol 2002;3:59‑62. 2. Ward HA, Russo GG, Shrum J. Cutaneous manifestations of antiretroviral therapy. J Am Acad Dermatol 2002;46: 284‑93. 3. Sharma A, Vora R, Modi M, Sharma A, Marfatia Y. Adverse effects of antiretroviral treatment. Indian J Dermatol Venereol Leprol 2008;74:234‑7. 4. Sharma A, Modi M, Sharma A, Marfatia YS. Cutaneous eruptions associated with nevirapine therapy in AIDS cases. Indian J Sex Transm Dis AIDS 2007;28:94‑6. 5. Hengge UR, Franz B, Goos M. Decline of infectious skin
Sinecatechins: A better prospect for treating anogenital warts Sir, Anogenital warts are the skin tumours caused by human papilloma virus (HPV) that may bother both the patients and their partners. Current treatment options are not satisfactory due to low efficacy and high recurrence rates. Although prophylactic vaccines have been recommended for adolescent women, more effective treatment modalities for anogenital warts are still needed. Topical Sinecatechins Ointment 15% is the first FDA approved botanical drug for treating anogenital warts.[1] Sinecatechins are a standardized extract of green tea leaves from Camellia sinensis, a species of the Theaceae family, containing polyphenols; particularly catechins (more than 85%). It contains eight different catechins and other green tea components. The main catechin in sinecatechins ointment his epigallocatechin gallate (EGCG), which has the highest biological activity.[2] Catechins exert multiple biologic activities by inhibiting a number of proteins, including enzymes involved in oxidative stress, blocking the kinases needed in tumour cell signalling and induction of apoptosis. These postulated mechanisms presumably contribute to the therapeutic effect of sinecatechins ointment. The proposed mechanisms of action of sinecatechins are:
Anti‑oxidant activity
The direct action of catechins is scavenging the reactive oxygen free radicals. Catechins may exert
manifestations in the era of highly active antiretroviral therapy. AIDS 2000;14:1069‑70. 6. Rodgers S, Leslie KS. Skin infections in HIV‑infected individuals in the era of HAART. Curr Opin Infect Dis 2011;24:124‑9.6. 7. Maurer TA. Dermatologic manifestations of HIV infection. Top HIV Med 2005;13:149‑54.7. Access this article online Quick Response Code:
Website: www.ijstd.org
DOI: 10.4103/0253-7184.132412
indirect antioxidant activity via inhibitory effects on transcription factors (e.g., nuclear factor‑κB [NF‑κB], activator protein‑1 [AP‑1]) and also inhibits the enzymes with activity that increases oxidative stress (e.g., lipoxygenases, cycloxygenases, and inducible nitric oxide). [3] EGCG also induces expression of endogenous antioxidant systems.
Anti‑proliferative activity
HPV E6 (early gene E6) degrades p53 (a tumour suppressor gene), inhibits the pro‑apoptotic protein BAK, activates telomerase and stabilizes Src‑family kinases. HPV E7 (early gene E7) inactivates Rb (a tumour suppressor gene). Conventionally, the Rb inhibits cell proliferation by binding to the E2F transcription factor (which controls the G1/S phase checkpoint of the cell cycle). Degradation of Rb by HPV E7 can result in uncontrolled cell division. A normal cell would react to this excessive cell division by p53‑dependent apoptosis; but the presence of HPV E6 prevents apoptosis by deactivation of p53 and BAK. The end result of their combined action (E6, E7) is cellular proliferation.[4] Catechins check the proliferation of cells by inhibiting kinases (receptor tyrosine kinases, telomerase) and promoting apoptosis.
Immuno‑stimulatory activity
HPV evades the immune system by reducing the expression of viral proteins in the immunogenic lower epithelial layers and decreased production of interferons. Catechins increase the activation of macrophages, lymphocytes, Langerhans cells and induction of cytokines (IL‑1β, TNF‑α, IFN‑γ), thereby eliciting cell‑mediated immunity against HPV. To conclude, not only has the sinecatechins had a wide spectrum of action but also the low recurrence
Indian Journal of Sexually Transmitted Diseases and AIDS 2014; Vol. 35, No. 1
75
Copyright of Indian Journal of Sexually Transmitted Diseases is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
