HIV Medicine - part 8 pdf

582 HIV and Renal Function 4. Benhamou Y, Bochet M, Thibault V, et al. Safety and efficacy of adefovir dipivoxil in patients co- infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet 2001, 358:718-723. 5. Benitez Bermijo, et al. Decreased glomerular filtration in HIV patients treated with tenofovir. Abstract TuPe2.3C21, 3th IAS 2005, Rio. 6. Blick G, Greiger-Zanlungo P, Garton T, Hatton E, Lopez RJ. Tenofovir may cause severe hypophos- phatemia in HIV/AIDS patients with prior adefovir-induced renal tubular acidosis. Abstract 718, 10th CROI 2003, Boston. 7. Breton et al. Tubulopathy consecutive to Tenofovir-containing antiretroviral therapy in two patients infected with Human Immunodeficiency Virus-1.Scand J Infect Dis 2004, 36: 527-528. 454. 8. Gallant et al. (TDF)Compared to Nucleoside Reverse Transcriptase Inhibitors (NRTIs); IAS 2005: Abstract TuPe2.3C18. 9. Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in com- bination therapy in antiretroviral-naïve patients: a randomized trial. JAMA 2004;292:191-201. 10. Gallant J, Parish M, Keruly J, Moore R. Decline in renal function associated with tenofovir DF com- pared with nucleoside reverse transcriptase inhibitor treatment. Abstract 820, 12th CROI, 2005, Bos- ton. 11. Gallais H, Lazzarin A, Adam A, et al. The Viread Expanded Access Program in Europe/Australia: summary of the safety and efficacy of tenofovir disoproxil fumarate in antiretroviral treatment experi- ence patients. Abstract TuPeB4552, 15th IAC, 2004, Bangkok. 12. Callens St et al. Fanconi-like syndrome and rhabdomyolysis in a person with HIV infection on highly active antiretroviral treatment including TNF. J Infection 2003, 47: 262-263. 13. Cheng A, Wulfsohn M, Cheng SS, Toole JJ. 2 year long term safety profile of tenofovir DF (TDF) in treatment-experienced patients from randomized, double-blind, placebo-controlled clinical trials. Ab- stract 156, 9th EACS 2003, Warsaw. 14. Chin-Beckford N, Kaul S, Jayaweera DT. Comorbidities drive nephrotoxicity associated with tenofovir fumarate: a case series from Florida. Abstract WePeB5970, 15th IAC 2004, Bangkok, 15. Coca St et al. Acute renal failure associated with TNF: Evidence of drug induced nephrotoxicity. Am J Med Sci 2002, 324: 342-344. 16. Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976, 16: 31-41. 17. Conaldi PG, Bottelli A et al. HIV-persistant infection and cytokine induction in mesangial cells: a potential mechanism for HIV-associated glomerulosclerosis. AIDS 2000, 14: 2045-2053. 18. Créput C, Gonzales-Canali G, et al. Renal lesions in HIV-1-positive patient treated with tenofovir. AIDS. 2003, 17:935-937. 19. Estrada V, Ena J, Domingo P, et al. Renal safety of tenofovir DF in HIV treatment-experienced pa- tients with adverse events related to NRTI use: a recover study. Abstract H-169, 44th ICAAC,2004, Washington. 20. Fellay J, Boubaker K et al. Prevalence of adverse events associated with potent antiretroviral treat- ment: a Swiss HIV cohort study, Lancet 2001 ,358: 1322-27 21. Franceschini et al. Incidence and etiology of acute renal failure among ambulatory HIV-infected pa- tients. Kidney International 2005, 67:393-403. 22. Gaspar G et al. Fanconi syndrome and acute renal failure in a patient treated with tenofovir: a call for caution. Aids 2004, 18: 351-352. 23. Grases F, Casta- Banza A, et al. Indinavir crystallization and urolithiasis. Int J Urology Nephrology 1999 ,31: 23 – 29. 24. Horberg MA, Klein DB, Yu J, Sinn K, Yu J. Effect of tenofovir on renal function in a "real world" clinic setting. Abstract WePpB2066, 15th IAC, 2004, Bangkok. 25. Inui KI, Masuda S, et al. Cellular and molecular aspects of drug transport in the kidney, Kidney Int. 2000 ,58: 904- 958. 26. Izzedine H, Hulot JS, Vittecoq D, et al. Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive HIV-1-infected patients data from a double-blind randomized active-controlled multicentre study. Nephrol Dial Transplant 2005, 20:743-6. 27. Jaegel-Guedes E, Wolf E, Ruemmelein N, et al. Incidence of tenofovir-related nephrotoxicity in a large outpatient cohort. Abstract WePeB5937,15th IAC 2004, Bangkok. 28. Johnson M, Grinsztejn B, Rodriguez C, et al. Atazanavir plus ritonavir or saquinavir, and lopina- vir/ritonavir in patients experiencing multiple virological failures. AIDS 2005,19:685-694. 29. Jones R, Stebbing J, Nelson M, et al. Renal dysfunction with tenofovir disoproxil fumarate-containing HAART regimens is not observed more frequently: a cohort and case-control study. J Acquir Immune Defic Syndr 2004; 37:1489-1495. References 583 30. Kopp JB, Miller KD, et al.Crystalluria and urinary tract abnormalties associated with indinavir. Annals Int Med 1997, 127: 119-125. 31. Karras A et al. Tenofovir related nephrotoxicity in human immunodeficiency virus- infected patients: three cases of renal failure, fanconi syndrome, and nephrogenic diabetis insipidus. CID 2003, 36: 1070-1073. 32. Kearney BP, Liaw S, Yale K, et al. Pharmacokinetics following single dose administration of tenofovir DF in subjects with renal impairment. Abstract P4, 6th Int Con Drug Ther HIV Inf 2002, Glasgow. 33. Kinai E, Hanabusa H et al. Renal tubular toxicity associated with tenofovir assessed using urine-beta 2 microglobulin, percentage of tubular reabsorption of phosphate and alcaline phosphatase levels. AIDS 2005, 19:2031-2041. 34. Klotman PE. HIV-associated nephropathy. Kidney Int 1999,56: 1161-1176. 35. Leen et al. Pharmacokinetics of enfurvitide in a patient with impaired renal function. CID 2004, 39:e119-e121. 36. Lewis S, Gathe J, Ebrahimi R, Flaherty J, Wallace RJ. Comparative evaluation of renal function in HIV-infected, treatment-naïve patients of African American descent receiving HAART regimes con- taining either tenofovir DF or zidovudine. Abstract TuPeB4599, 15th IAC 2004, Bangkok. 37. Louie S, Ballard C, Bi L, Beringer P. Factors increasing the risk of renal dysfunction with tenofovir difumarate (TDF). Abstract TuPe3.5B01, IAS 2005, Rio de Janeiro. 38. Malik et al. Acute renal failure and fanconi syndrome in an AIDS patient on tenofovir treatment-case report and review of literature. J Infect 2005, 51: E61-65. 39. Marras D, Bruggeman L A et al. Replication and compartmentalization of HIV-1 in kidney epithelium of patients of HIV-associated nephropathy. Nature medicine 2002, 8: 522-526. 40. Mauss S, Berger F, Schmutz G. Antiretroviral therapy with tenofovir is associated with mild renal dysfunction. AIDS 2005, 19:93-95. 41. Molina JM, Gathe J, Lim PL, et al. Comprehensive resistance testing in antiretroviral naïve patients treated with once-daily lopinavir/ritonavir plus tenofovir and emtricitabine: 48-week results from study 418. Abstract WePeB5701,15th IAC 2004, Bangkok. 42. Murphy MD et al. Fatal lactic acidosis and acute renal failure after assition of tenofovir to an antiretro- viral regimen containing didanosine. CID 2003, 36: 1082-1085. 43. Nickeleit V, Klimkait T, Binet IF et al. Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy. NEJ; 2000, 342: 1309-1315. 44. Padilla et al. Low frequency of renal function impairment during one-year of therapy with tenofovir- containing regimens in the real-world:A Case Control Study. AIDS Pat Care STDs 2005, 19:421-424. 45. Peyriere H, Reynes J, Rouanet I, et al. Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. J Acquir Immune Defic Syndr. 2004,35:269-273. 46. Reisler R, Jacobson L, Gupta S, et al. Chronic kidney disease and the use of HAART. Abstract 818, 12th CROI 2005, Boston. 47. Roca B, Gisbert C, Cabestany B, Perez AP, Ventura JM. Metabolic and renal profile before and after tenofovir DF. Abstract B10708, 15th IAC, 2004, Bangkok. 48. Rollot F et al. Tenofovir-related fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodefiency syndrome: The role of lopinavir-ritonavir-didanosine. CID 2003: 37. 49. Rodriguez-Gomez et al. Tenofovir-related fanconi syndrome in HIV positive patients: The role of interaction with other antiretroviral drugs. Abstract TuPe2.4C06, IAS 2005, Rio. 50. Schooley RT, Ruane P, Myers RA, et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS 2002, 16:1257-1263. 51. Scott JD, Wolfe PR, Quiros J, Behrooznia E, Buyer B, Bolan RK. Rare occurrence of renal toxicity when retrospectively evaluating the use of tenofovir DF in 2 clinical practices. Abstract TuPeB4532, 15th IAC, 2004, Bangkok. 52. Squires K, Pozniak AL, Pierone G, et al. Tenofovir DF in antiretroviral-experienced, nucleoside- resistant HIV-1 infected patients with incomplete viral suppression. Ann Int Med 2003, 139:313-320. 53. Stephens EB, Tian C, et al. Simian-immunodefeciency virus-associated nephropathy in macaques: AIDS Research Vol. 16, 13: 1295- 1306. 54. Stephens E B, Tian C et al. Rhesus macaques infected with macrophage-tropic simian immunodefi- ciency virus exhibit extensive focal segmental and global glomerulosclerosis. J Virology 1998, 72: 8820-8832. 55. Szczech LA. Renal diseases associated with human immunodeficiency virus infection: epidemiology, clinical course and management, CID 2001, 33:115-119. 56. Wali RK, Drachenberg CI et al. HIV-1-associated nephropathy and response to highly-active antiret- roviral therapy. Lancet 1998, 352:783-784. 584 HIV and Renal Function 57. Winston JA, Bruggeman LA et al. Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. NEJM 2001 , 344: 1979-1984. 58. Winston et al. Minor changes in calculated creatinine clearance and anion-gap are associated with tenofovir DF containing highly active antiretroviral therapy. Abstract TuPe2.3C23, IAS 2005, Rio. Introduction 585 21. HIV-associated Skin and Mucocutane- ous Diseases Helmut Schoefer, Dana L. Sachs, Falk Ochsendorf Introduction Since 1981, when the first reports about AIDS were published in medical literature, skin and mucocutaneous diseases played an important role in the clinical diagnosis of acquired immunodeficiency. Kaposi’s sarcoma in young homosexual men was the first symptom that made AIDS a visible disease (Friedman-Kien 1981, 1990). Additionally, opportunistic infections of the skin and oral cavity such as herpes simplex and candidiasis were published as being clinical markers of acquired im- munodeficiency (Gottlieb 1981, Siegal 1981). In the early years of HIV infection, a broad spectrum of common cutaneous infections was noted in patients due to vi- ruses, bacteria, fungi, protozoa, and parasites as well as many unusual manifesta- tions of common dermatoses (Friedman-Kien 1989, Farthing 1989, Schöfer 1990, Schöfer 1991, Berger 1997). The alterations of the cell-mediated immune system enable organisms considered to be non-pathogens to penetrate into the tissue and cause infections. Such opportun- istic infections, as well as any other infections in the immunodeficient host, some- times behave aggressively leading to a life-threatening clinical course. The most frequent skin diseases documented in a prospective long-term study in HIV-infected patients at the Department of Dermatology and Venereology, Univer- sity Hospital, Frankfurt/M, Germany, between 1983 and 2004, are summarized in Table 1. Differences in the prevalence and incidence of mucocutaneous disease between countries may be attributable to climate, endemic diseases, hygienic standards and the availability of specialized medical facilities and drugs, as well as social, eco- nomic and cultural factors. The risk groups observed – homosexual men, IVDA, heterosexuals, and children – play an important role in the incidence and prevalence of HIV-associated mucocutaneous diseases (Tzung 2004, Geoghagen 2004, Shi- mizu 2000, Munoz-Perez 1998, Sivayathorn 1995, Smith 1994, Pallangyo 1992). Among sexually transmitted diseases, chancroid is an important indicator of the spread of the HIV epidemic in tropical and subtropical regions; whereas in Europe, herpes simplex infections and a resurgence of syphilis in homosexual men are more important indicators. Recently, there has been increased reportage of lympho- granuloma venereum, an STD caused by Chlamydia trachomatis (L1-3), in homo- sexual men in several big cities throughout Europe. It is suspected that this is due to the changing sexual behavior of homosexual men during the past 5 to 7 years. Fear of acquiring HIV infection by unsafe sexual practices has lessened as patients live longer, healthier lives on HAART therapy. There may be a sense among patients that HIV infection no longer confers a death sentence because HAART decreases viral loads resulting in fewer diseases. In addition, many men are not aware of the risk of infection through orogenital contact with other STDs such as syphilis. 586 HIV-associated Skin and Mucocutaneous Diseases Table 1: Frequency of skin diseases No. patients % of all HIV patients Oral candidiasis 636 30% Seborrheic dermatitis 619 28% Xeroderma 600 28% Tinea 502 23% Folliculitis 492 23% Syphilis (active/seropositive) 485 23% Kaposi's sarcoma 460 21% Pruritus 436 20% Genital warts 368 17% Candida infections, others 355 16% Drug eruptions 349 16% Herpes simplex genitoanalis 349 16% Herpes zoster 345 16% Gonorrhea (active/history) 340 16% Bacterial infections 315 15% Mollusca contagiosa 301 14% Warts (HPV) 278 13% Herpes simplex labialis 214 10% Oral hairy leukoplakia 188 9% Hair loss 135 6% Psoriasis 117 5% Basal cell carcinoma (BCC) 25 1.2% Squamous cell carcinoma (SCC) 23 1.1% Malignant melanoma 9 0.4% Total number of patients 1982 - 2000 2149 100% Notice: The frequency of skin diseases listed here mirrors the clinical symptoms of 2149 HIV- infected patients, who visited the Frankfurt University Hospital between 1982 and 2000 be- cause of skin problems. Most of these patients were referred with a known HIV infection. Oth- ers were detected to be HIV-positive by their dermatological symptoms, which were interpreted as clinical markers of severe acquired immunodeficiency and led to HIV antibody testing. The majority of these patients (75 %) was seen in the pre-HAART era (between 1982-1996). Since 1996, more than 80 % of the patients living with HIV/AIDS in Frankfurt/M. are on HAART. This led to a significant reduction in opportunistic skin diseases (by 90 %) and Kaposi’s sarcoma (by 90 %). The high frequency of skin disease summarized in this table is still seen in patients who are not on HAART or not yet diagnosed to be HIV-infected. In urban areas, syphilis is now seen 4 to 10 times more frequently in homosexual men in comparison to 2000. Until today, there has been no observable increase in the incidence and prevalence of syphilis in European women, but it is very likely that the epidemic in homosexual men will be followed by a heterosexual epidemic within a few years. According to the epidemiological data, provided by the Robert Koch Institute in Berlin, the registration of new syphilis cases exceeded the number of newly registered HIV infections in 2003 by more than 1000 cases (RKI 2003). Dermatological examination and therapy in HIV-infected patients 587 It has become evident that a functional cell-mediated immune system plays an im- portant role in the protection against epithelial tumors. The likelihood of developing squamous cell carcinomas, basal cell carcinomas, lymphomas, or even malignant melanoma is correlated with the length of time HIV-infected immunocompromised patients survive. Nowadays, HIV-infected patients survive longer than patients from the pre-HAART era. For this reason, these patients need to be monitored for primary cutaneous malignancies such as basal cell carcinoma, squamous cell carci- noma, melanoma, and cutaneous lymphomas. Analogous to the long-term immunosuppressed organ transplant recipient, the HIV- infected patient has to be examined periodically for melanoma as well as non- melanoma skin cancers including actinic keratoses (Schöfer 1998). Factors such as UV-light, smoking and oncogenic viruses (especially mucocutaneous infections with HPV 16 and HPV 18) must be considered as cofactors in carcinogenesis. Skin cancer precursors such as actinic keratoses, bowenoid papulosis, Bowen’s disease, and intraepithelial neoplasias of the genital or anal region must be treated early and aggressively. The incidence of anal carcinoma, an epithelial tumor typically found in old men, is now increasing in young HIV-infected homosexual men. It seems that the total duration, rather than the severity of immunodeficiency is important for the manifestation of these tumors. As in non-immunocompromised patients, risk factors such as pigmentation characteristics, sun sensitivity, sun exposure behavior patterns, and geographic location must be considered in the evaluation. Dermatological examination and therapy in HIV- infected patients HIV-infected patients with advanced disease often suffer from common skin dis- eases (Table 1), but they also present with rare dermatoses, unique to HIV infection. Careful dermatologic evaluation may lead to the diagnosis of serious systemic in- fections in this population such as cryptococcosis, bacillary angiomatosis, oral hairy leukoplakia, and Penicillium marneffei infections of the skin. Common dermatoses often present with atypical findings and may pose diagnostic dilemmas. For exam- ple, herpes simplex labialis may present as large superficial erosions or deeply ul- cerating lesions rather than the classical small vesicles on an erythematous base. Eruptions of secondary syphilis may ulcerate and form rupial lesions accompanied by high fever and constitutional symptoms (malignant syphilis). It is therefore im- portant to pursue diagnosis of all cutaneous eruptions through appropriate tests such as tissue cultures, biopsy, and swabs of lesions prior to the initiation of therapy. Because HIV-infected patients are at high risk of contracting other STDs due to the common modes of transmission, they should be screened for them. During the past three years, 39 % of all syphilis patients who attended our Department, had HIV co- infection. Dermatologic evaluation should include complete cutaneous inspection, oral cavity examination, inspection of the anogenital region and palpation of the lymph nodes. Standard treatment regimens for skin and mucocutaneous diseases may be inadequate in HIV-infected patients due to unusual strains of organisms leading to drug resistance. In these cases, high dose regimens or second and third line therapies may have to be considered (Osborne 2003). Diagnostic and therapeu- 588 HIV-associated Skin and Mucocutaneous Diseases tic regimens of the most frequent HIV-associated skin diseases are compiled in al- phabetical order in Appendix 1 of this chapter. Table 2: Clinical Diagnostic Tools Indication Performance Interpretation Presumptive diag- nosis of ulcers (mainly of syphilitic ulcers) Exudative lesions (condylomata lata, possibly secondary syphilis lesions). Dark-field microscopy Secretion (mechanical pressure, if necessary use ether in local anesthesia) of serous exu- date is applied to a glass slide, covered with a coverslip. Examination by dark-field micros- copy (1000x). Lesions in the mouth: examination not possi- ble due to saprophytic bacteria Negative test does not exclude syphilis; false negative testing may be due to: prior treat- ment with antibiotics/ antiseptics A positive test confirms the diagnosis Differential diagno- sis of tumors, skin lesions without defi- nite clinical diagno- sis, or to confirm a clinical diagnosis Biopsy Under local anesthesia: 4-mm punch-biopsy; if necessary: excisional biopsy. Fixation of the material in 10 % formalin; for special investi- gations (immunohistology, electron- microscopy, HPV-typing) use only saline. Dermatopathologist Presumptive diag- nosis of dermato- phytosis Skin-scraping for KOH examination Clean the skin with 70 % alcohol, let it dry. Use a scalpel or glass slide to scrape scales at the active edge onto a glass slide. A drop 10 - 20 % KOH is put on top of the specimen and covered with a cover slip. After ~ 20 mi- nutes or immediately after gentle heating the specimen can be examined microscopically (10-40x magnification) for fungal elements. The specimen may be cultured as well. Fungal elements (spores and hyphae) are not digested by KOH and can be visu- alized with light mi- croscopy. Presumptive diag- nosis of herpes infections (grouped vesicles or ulcers) Herpes-virus detection A smear of cells from the base of the skin lesion is taken (for culture: special swabs: Culturette™; use pressure to obtain cells). Sample can be put onto a glass slide for im- mediate direct fluorescent antibody testing (DFA) which will distinguish between HSV and VZV infections. Tzanck-preparation: multinucleated giant cells (Giemsa- or Wright-stain; 400x magnification) Viral lab, positive cul- ture proves diagno-sis; demonstration of DNA or antigen does not differentiate between living and dead viruses Drug eruptions, presumptive allergic contact dermatitis Allergy testing Serology: (RAST, lymph. transformation test); skin tests Type I reactions: Prick- and intra- cutaneous-tests. Type IV reactions: “Scratch”- and patch testing. A specialist in allergy should perform tests and interpretation. Allergist HAART: Influence on (muco-) cutaneous diseases 589 HAART: Influence on (muco-) cutaneous diseases The introduction of HAART in 1996 revolutionized the dermatological manage- ment of HIV-infected patients. Opportunistic infections and the clinical manifesta- tions of Kaposi’s sarcoma abated to a level of 10 % compared to the pre-HAART era (Reinmöller 1997, Schöfer 1998, Sepkowitz 1998, Calista 2002). An Italian hospital reported that HAART had reduced the total number of HIV patients with skin problems by 40 %. The percentage of patients with cutaneous infections dropped from 66 to 53 %; the percentage of non-infectious, inflammatory diseases from 25 to 21 %; however, the percentage of patients with drug reactions increased from 8 to 23 % (Calista 2002). Appendix 2 is a compilation of antiretroviral drugs, and their cutaneous side effects. Atypical clinical courses of skin diseases and re- sistance to therapy, which were very common in patients with severe immunodefi- ciency in the pre-HAART era, are rare conditions now. They still occur, however, in patients not taking antiretroviral therapy (Mirmirani 2001). Cutaneous infections and inflammatory skin diseases have been replaced by drug eruptions caused by almost 20 currently available antiretroviral drugs. In some patients, immune system reconstitution, following 1 to 2 months after the introduction of HAART, causes clinical disease summarized as immune reconstitution inflammatory syndrome (IRIS). Drug eruptions have many clinical patterns including macular or maculopapular exanthemas, follicular eruptions, urticaria, and toxic epidermal necrolysis (TEN), to name a few. Severe, sometimes life-threatening reactions such as Stevens-Johnson- syndrome or TEN were mainly reported in patients on combination therapy with zidovudine, didanosin, nevirapine, indinavir or amprenavir. In 86 % of these pa- tients, the drug eruptions occurred within the first 4 weeks of treatment (Rotunda 2003). Instead of discontinuing therapy, less severe drug eruptions without mucosal involvement, blistering, or constitutional symptoms (apart from pruritis), may be treated with antihistamines and corticosteroids. This is especially important for pa- tients, whose choice of antiretroviral combination drugs is already limited by drug resistance or severe side effects such as hematotoxicity or polyneuritis. Patients who are “treated through” drug eruptions must be monitored frequently. Cortico- steroid treatment should not exceed the equivalent of 1 mg/kg/d bodyweight of prednisone. Blister formation, involvement of the mucous membranes and constitutional symp- toms (hypersensitivity syndrome) are absolute indications to stop antiretroviral therapy. TEN (e.g. induced by efavirenz, nevirapine) and hypersensitivity syndrome (e.g. induced by abacavir) may be fatal. Drug interactions between HAART and agents used to treat cutaneous diseases are frequent and need to be carefully evaluated before being prescribed (see Chapter “Drug interactions”, McNicoll 2004). Azole derivatives, retinoids and drugs me- tabolized via the p450 pathway frequently interact with antiretrovirals. Immunosuppressive therapies, such as ultraviolet light and cyclosporin, should be limited to a few conditions such as severe autoimmune diseases, and used only with careful clinical and laboratory monitoring. Photo(chemo)therapy is able to provoke viral infections such as herpes zoster and herpes simplex, epithelial tumors, and to increase the HIV viral load. Despite this, we have seen the benefit of UVB 311nm phototherapy in HIV-infected patients with extreme pruritus associated with papu- 590 HIV-associated Skin and Mucocutaneous Diseases lar dermatoses or eosinophilic folliculitis, resistant to all other therapies. As long as these patients were under the protection of HAART, UV therapy caused no observ- able worsening of the immune status. Eliciting the cause of a drug eruption can be challenging, especially if the patient is taking complementary medication not prescribed by a physician. It is necessary to ask explicitly whether any herbal medicines, vitamins, minerals, or food comple- ments are being taken to improve the general health. Substances with a potential risk of sensitization or toxicity can be the cause of drug reactions (Witkowski 2003). Urticaria, angioedema, and exanthemas due to food complements are re- ported in the literature (Gised 1996). The treatment of KS varies with the clinical manifestation of the tumor, the immune status of the patient and his additional symptoms associated with the HIV infection (details see Chapter “Kaposi’s sarcoma”). Conclusions The dermatologist’s role in the care of HIV-infected patients is to be familiar with HIV-associated skin and mucocutaneous diseases, their diagnoses, and manage- ment. It is also a part of the extensive interdisciplinary knowledge necessary for any physician who takes care of HIV-infected patients. Considering the lifelong duration of antiretroviral therapy with complications such as drug intolerance, development of epithelial tumors induced by UV-light expo- sure or oncogenic viruses, it is recommended that patients have a dermatologic con- sultation before the start of antiretroviral therapy. Complete skin examination with attention to the presence of STDs should be performed. Education should include prevention of photodamage, safe sex practices, and skin care to avoid infections, especially when HIV-associated xerosis is already evident. Despite the fact that HIV-associated opportunistic infections are less frequent in the HAART era, knowledge about these diseases and adequate treatment is still of high clinical relevance. The full spectrum of these skin diseases is still found in untreated patients around the world. Dermatological markers of disease of severe acquired immunodeficiency (see Ap- pendix 1) play an important role in this situation (Schöfer 1991), especially if sev- eral diseases are diagnosed in the same patient. In the absence of other immunode- ficiency, HIV antibody testing must be offered to the patient as a diagnostic tool to elicit the cause of the clinical presentation. At present, syphilis and HIV co-morbidity is of special interest. The incidence of syphilis in Western Europe has increased 4 to 10 times over the past 4 years. As HIV and Treponema pallidum share the same route of transmission, any patient with syphilis must be checked for HIV infection. The delayed seroconversion for HIV antibodies should be taken into account and, if initially negative, HIV testing should be repeated after 3 months. Most frequent HIV-associated skin diseases 591 Appendix 1: Most frequent HIV-associated skin diseases Acute HIV exanthema: In 40-90 % of all patients infected with HIV-1, an acute, febrile, mononucleosis-like disease with constitutional symptoms and an exanthema occurs (details see Chapter “Acute HIV-1 Infection”). This nonspecific eruption starts 1 to 3 weeks after HIV transmission, and several weeks before HIV serocon- version. The macular exanthema favors the upper trunk and is characterized as fairly non-pruritic with erythematous macules from 0.5 to 1 cm in diameter. Mor- billiform or rubella-like eruptions and palmoplantar hyperkeratotic eczema occur less frequently. Histopathology reveals a nonspecific perivascular and interstitial infiltrate in the upper and mid dermis (Barnadas 1997). Oral aphthous ulcers, fre- quently in combination with shallow genital ulcers (bipolar aphthosis) are another important clinical sign (Hulsebosch 1990, Porras-Luque 1998). Differential diagno- sis includes other viral infections (EBV, CMV), Mediterranean spotted fever (Se- gura 2002), secondary syphilis, drug eruptions (Hecht 2002, Daar 2001) and Beh- cet’s disease. Aphthous ulcers: At least three different kinds of aphthous ulcers occur in the oral cavity of HIV-infected patients. The most frequent diagnosis is recurrent aphthous stomatitis (canker sores) (1) with single or few painful lesions usually localized in the vestibule of the mouth. The ulcers occur at sites of mechanical injuries, are 3 to 10 mm in diameter and heal spontaneously after a few days. Single or multiple large aphthae (2) which are >1cm in diameter and usually persist for several weeks are less common. Both variants are of unknown origin (Rogers 1997). In a few cases, especially when multiple small lesions occur, herpes simplex viruses can be involved. Large ulcers in combination with severe immunodeficiency can be caused by cytomegaloviruses, which are usually part of a generalized CMV infection. Bi- polar aphthosis (3), involving the oral and genital mucosal membranes, is an im- portant clinical symptom of acute HIV infection or Behcet’s disease. In addition to these clinical variants of aphthous ulcers, several authors have discussed the direct role of HIV retroviruses in aphthous stomatitis (Kerr 2003). The treatment of recur- rent aphthosis is based upon topical anesthetics, and corticosteroids. Large persis- tent aphthae can require intralesional corticosteroids or systemic prednisone. Im- munomodulators, such as thalidomide, are suggested for use as prophylaxis in pa- tients with frequent and painful recurrences. Folliculitis: pustular, papular or edematous-papular follicular lesions, involving the proximal limbs and the upper trunk. Possible causes include Staphylococus, Malas- sezia furfur, Demodex folliculorum, and drugs such as indinavir. Treatment depends on the etiologic agent detected by bacterial swabs and histopathology if needed. Antimicrobials against staphylococcus, and malassezia, or changing the antiretrovi- ral drug regimen may be required. DADPS, a 10 % crotamiton or polidocanol oint- ment, or low-dose UV-311nm radiation are effective against severe pruritus in these patients (Holmes 2001, Simpson-Dent 1999). Today, it is well established that [...]... http://amedeo.com/lit.php?id =86 2 182 8 126 Ramirez-Amador V, Esquivel-Pedraza L, Sierra-Madero J, et al The changing clinical spectrum of HIV- related oral lesions in 1,000 consecutive patients: A 12-Year study in a referral center in Mexico Medicine (Baltimore) 2003; 82 :3 9-5 0 http://amedeo.com/lit.php?id=12544709 127 Reichart PA Oral ulcerations in HIV infection Oral Dis 1997; Suppl 1:S 18 0-2 http://amedeo.com/lit.php?id=9456 685 ... 60 8- 1 0 http://amedeo.com/lit.php?id=1530419 81 Kaye BR Rheumatologic manifestations of infection with human immunodeficiency virus (HIV) Ann Intern Med 1 989 ;111:15 8- 6 7 http://amedeo.com/lit.php?id=266 284 9 82 Kerr AR, Ship JA Management strategies for HIV- associated aphthous stomatitis Am J Clin Dermatol 2003; 4:66 9 -8 0 http://amedeo.com/lit.php?id=14507229 83 Klencke BJ, Palefsky JM Anal cancer: an HIV- associated... Acad Dermatol 19 98; 39:4 8- 5 5 http://amedeo.com/lit.php?id=9674397 1 68 Stern RS, Steinberg LA Epidemiology of adverse cutaneous reactions to drugs Dermatol Clin 1995,13: 68 1 -8 http://amedeo.com/lit.php?id=7554515 169 Taiwo BO Use of thalidomide in HIV infection AIDS Read 2001, 11:51 1-5 13, 51 8- 9 , 52 3-4 http://amedeo.com/lit.php?id=117 080 84 170 Tangsinmankong N, Kamchaisatian W, Lujan-Zilbermann J et al... 1 989 ; 21:49 7-5 05 http://amedeo.com/lit.php?id=2 587 953 101 Moses S.Pruritus Am Fam Physician 2003; 68: 113 5-4 2 http://amedeo.com/lit.php?id=14524401 102 Munoz-Perez MA, Rios-Martin JJ, Rodriguez-Pichardo A, Camacho F.Cutaneous T-cell lymphoma and HIV infection: 2 cases and a review of the literature Acta Derm Venereol 1999; 79:15 3-1 55 http://amedeo.com/lit.php?id=102 286 39 103 Munoz-Perez MA, Rodriguez-Pichardo... immune reconstitution syndrome in an HIV- infected patient: successful treatment with doxycycline Clin Infect Dis 2003; 36:162 8- 9 http://amedeo.com/lit.php?id=1 280 2773 107 Orrick JJ, Steinhart CR Atazanavir Ann Pharmacother 2004, 38: 166 4-7 4 1 08 Osborne GE, Taylor C, Fuller LC The management of HIV- related skin disease Part I: infections Int J STD AIDS 2003; 14:7 8- 8 6 http://amedeo.com/lit.php?id=12716492... valacyclovir J Infect Dis 2003; 188 :88 3-9 0 http://amedeo.com/lit.php?id=12964120 179 Ward HA, Russo GG, Shrum J Cutaneous manifestations of antiretroviral therapy J Am Acad Dermatol 2002; 46: 28 4-9 3 http://amedeo.com/lit.php?id=1 180 7442 180 Weitzul S, Duvic M HIV- related psoriasis and Reiter's syndrome Semin Cutan Med Surg 1997,16:21 3 -8 http://amedeo.com/lit.php?id= 9300632 181 Witkowski JA, Parish LC Dermatologic... al , Primary HIV type-1 infection misdiagnosed as Mediterranean spotted fever Eur J Clin Microbiol Infect Dis 2002,21:47 8- 9 http://amedeo.com/lit.php?id=121116 08 152 Sepkowitz KA Effect of HAART on natural history of AIDS-related opportunistic disorders Lancet 19 98; 351:22 8- 3 0 153 Shapiro DL, Masci DR Treatment of HIV associated psoriatic arthritis with oral gold J Rheumatol 1996; 23: 181 8- 2 0 http://amedeo.com/lit.php?id =88 95167... 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