Review Dermatoses in the AIDS Dermatoses in tile AIDS L. Olmos Acebes and M.A. Gonzales Intxaurraga SUMMARY The authors report shortly on their experience in diagnosing and treating skin manifestations in the early and late stages of HIV infection. They believe that by careful observation of skin symptoms it is possible to suspect with great probability the HIV infection. According to their experience they range the symptoms into three major groups. The most frequent disorders: seborrheic dermatitis, candidiasis, condyloma accuminatum, herpes simplex, Kaposi's sarcoma, and dermatophytosis. Dermatoses with aggressive course: syphilis, cutaneous leishmaniasis, necrotising folliculitis, necrotising gingivitis, herpes zoster, molluscum contagiosum, scabies and papular pruritic eruption. Exceptional dermatoses: psoriasis, oral hairy leukoplakia, and prurigo. This review was prepared in order to help the dermatologists and general practitioners in screening the HIV positive patients. Introduction About 90% of patients infected with the Human Immunodeficiency Virus (HIV) present some mani- festation on the skin and mucous membranes (1,2), which can be not strictly assigned to the different stages of this infection: the asymptomatic HIV positive patients, those affected by the AIDS Related Complex (RCA), and patients with expressed AIDS. Contrary to the symptoms in the early stages of HIV infection, the manifestations in fully expressed AIDS are less characteristic compared to the symptoms observed in routine dermatological cases. Skin disorders in these patients may appear atypical, they may be widespread, have a more prolonged cour- se, and the response to treatment may be poorer than expected. Some years ago the World Hea!tli. Organization (WHO) recommended including the HIV infection into Sexually Transmitted Diseases (SID). The Human Immunodeficiency Virus presents the same multidisci- plinary, epidemiological, preventive, and social prob- lems, which fact justifies WHO decision. Acta Dermatoven APA Vol 10, 2001, No 1 - --------------------------------- 9 Dermatoses in the AIDS Clinical observations Most jrequent dennatoses Seborrheic dermatitis (SD) Seborrheic dermatitis (SD) is without doubt the most common dermatosis in HIV-infected patients and is often the only sign of infection occurring in up to 50% of cases (2). Clinically SD is characterized by a mild to severe erythema with irregular shape, whitish or yellowish sca- les and a greasy appearance, involving the seborrheic skin regions: the scalp, temples, retroauricular folds, outer parts of the ears , eyebrows, eyelids, glabella, nasolabial folds, and the midline areas of the chest and back. Less frequently intertriginous spaces are involved and widespread lesions may occur. The course is usually chronic. The histopathologic findings are similar to those seen ip non HIV-infected individuals. Although SD is always associated with a consti- tutional seborrheic state and the clinical findings worsen as the disease progresses, and clear as the immune situation improves, this is due to infection to Pityro- sporum ovale or Pityrosporum orbiculare (3). The treatment is essentially local with shampoos containing imidazoles, corticosteroid creams and hygienic measures. Oropharyngeal candidiasis (OC) Candida albicans is a facultative pathogenic sapro- phyte and in 60% of normal individuals colonizes the oropha1yngeal tract, but in HIV-seropositive patients this may be a valuable marker indicating a compromise of defense mechanisms of the mucosa. Oral candidosis is the most common infection in HIV-infected patients. It is evident that this infection can also be located on other mucosal surfaces like the gland, the corona1y sulcus of penis, the vagina or anus, and even in the cutaneous folds and nails, but the relation withAIDS is more difficult to interpret (4, 5). Dissemina- ted candidiasis in severely immunocompromised HIV- infected patients has rarely been reported, but it is usually fatal. Clinically there are small white lumps which, when removed, leave an underlying erythematous base loca- ted on the buccal epithelium of the cheeks, gums, palate or of tongue. In severe cases, extension to the pharynx or to the oesophagus may occur and erosive complica- tions commonly cause severe symptoms resulting in inadequate food intake. The treatments are always deceiving due to the frequent relapses despite the good immediate effects . Fig. 1 Condyloma acuminatum giganteum. Therefore a simultaneous local and oral treatment with flutrimazol , itraconazol, piroxolamin or fluconazol has to be used. Condyloma accuminatum (CA) After SD and OC condyloma accuminatum is the third most common cutaneous affection in HIV-infected patients , detected in more then 30% of the seropositive individuals (6). The clinical patterns that can be seen comprehend all the spectra known. In the early HIV disease , the clinical manifestations, clinical course and response to treatment are not unusual. With moderate or advanced immunodeficiency, the HPV lesions may become con- Fig.2. Cutaneous leishmaniasis nasal aria. R eview 10 - --------- ------ ------------------- Acta Dermatoven APA Vol 10, 2001, No 1 R eview Fig. 3. Necrotizing folliculitis. fluent, much more numerous, unresponsive to usual treatment, and may appear in unusual places (Fig. 1). Unfortunately, no therapy has been devised to era- dicate HPV entirely; thus it is necessary to use a com- bined local treatment. A variety of antimitotic agents are widely employed like podophyllin resin, purified podophyllotoxin or 5-fluorouracil. Surgety, cryotherapy, e lectrocoagulation, lasertherapy, and intralesional Fig.4. Papular pruritic eruption. Dermatoses in the AIDS interferon-alpha are also standard measures used far HPV infection (7). Recently new topics, such as imi- quimod or 3% cidofovir ointment, have been success- fully used. Herpes simplex (HSV) In patients w ith AIDS the herpes simplex virus, type 2 infection has a prevalence of nearly 20% ( 4, 8). The clinical signs of the genital herpes rarely allow to suspect the immunodeficiency, ~hough in cases of a significant immunosuppression the lesions may run a prolonged and atypical course with more destructive nerve lesions or a very chronic course, even with an appropriate therapy. Among the most remarkable complications, besides erythema multiforme, the disseminated or systemic infection has to be mentioned. It appears, however, with severe immunodeficiency. The treatment of choice for the HSV infection is Valaciclovir, an aciclovir prodrug, with a better oral availability. The use of a topical antiseptic may help to reduce the risk of secondary bacterial infection. In severe HSV infection , possibly resistant to aciclovir, systemic phosphonoformate (Foscarnet) may be considered. Kaposi's sarcoma (KS) KS is a vascular neoplastic disorder and it is observed much more frequently in homosexuals than in intrave- nous drug users. KS is caused by the infectious agent HHV-8 (Human Herpes virus Type 8) that has been shown to be transmitted sexually (9). The prevalence in Spain does not exceed 6% of the HIV-infected persons, contrary to what it happens in most countries worldwide where 11 % of seropositives can be observed (10), though this prevalence has dro- pped significantly (11). The treatment of this neoplasm has been based on Interferon alpha. However, at present the combined treatment with two virostatics and a protease inhibitor (HAART) is recommended. Dermatophytosis Up to 20% of HN-infected persons have dermato- phyte infections. This prevalence is similar to that seen in HIV non-infected individuals. Aggressive dennatoses Practically ali the dermatological pathology can be observed during the evolutionary stages of AIDS. Acta Dermatoven APA Vol 10, 2001, No 1 - - --- --- ---- ----- - - - - ---- - - ---~ - - -- 11 Dermatoses in the AIDS Syphilis (S) Syphilis is quite frequent in patients with HIV infection, with a prevalence of 18-30%. The symptoms of this oldest and best-known sexually transmitted disease in AIDS patients are less characteristic and thus more difficult to diagnose. Atypical clinical and serological findings are frequent. Examples include rapid progression from the primary chancre to the later stages of S. maligna and widespread gummata. The central nervous system manifestations are more frequent and more severe (12, 13). The Treponema pallidum has never shown resistance to penicillin and continues to be the treatment of choice. Cutaneous leishmaniasis (CL) The main area of overlap is Southern Europe, espe- cially Spain. The clinical manifestations, though really aggressive, are not displaying necrosis. The lesions are situated in exposed areas, but the inoculation point is sometimes undetectable. The granulomatous lesions are usually spreading (Fig. 2). Making a smear of material from the sore and stai- ning it with Giemsa on a microscope slide can confirm the infection by demonstration of the parasite while histopathology confirms histiocytes full of Leishmania with lymphocytic reaction that possibly facilitates the extension of injuries and even of the scattering (14). The treatment with pentavalent antimonials is efficient. Necrotizing folliculitis (NF) All the pyogenic bacterial infections are commonly encountered in HIV patients with a prevalence of 3- 11 o/o of cases. Much more rare is the NF that is manifested as suppurative or abscess-like lesions with serohematic and blackish scabs developing in 2-3 days from isolated pustules. The lesions may be scattered anywhere on the skin (Fig. 3). Generally, there is not a defined bacteriology, and the healing is slow and unaesthetic (15). NF is treated with the application of topical antisep- tics with good results, but in general it resolves with unaesthetic scars. Necrotizing gingivitis (NG) A mixed flora like the fusospyrochetae complex, candida, gram-positive cocci, herpes virus, cytome- galovirus, and other organisms may cause acute necrotizing gingivitis in immunocompromised host. The clinical manifestations, including gingival sore- ness, bleeding and halitosis may develop into necrosis 12 Fig. 5. Prurigo, a detail. and destructions with loss of teeth and further functional problems. There is often enlargement of the cervical lymph nodes with pyrexia and malaise. The treatment is complicated because to the topical antiseptics we have to add antivirals like valaciclovir, metronidazole or penicillin depending on the gravity and the etiology. Fig. 6. Perianal prurigo. Review Acta Dermatoven APA Vol 10, 2001, No 1 Review Herpes zoster (HZ) According to the few publications, the prevalence oscillates between 6 ancl 9% of HIV-infectecl persons. HZ in HIV-infected patients is more serious than similar infections in immunocompetent hosts, because painful atrophic scars, persistent ulcerations, multi- dermatomal involvement, recurrent zoster infections, ancl seconcla1y episocles of varicella may be seen. Severe pain ancl persistent postherpetic neuralgia may also develop. The treatment is with one of the thymicline kinase inhibitors, such as acyclovir, valacyclovir, ancl famcy- clovir ( 4, 8). Resistant cases require treatment with intra- venous application of foscarnet. Molluscum contagiosum (MC) MC is usually a benign viral infection. However, in immunocompromisecl patients it may become wicle- spread, disfiguring and unresponsive to treatments. Sometimes other cutaneous clisorclers (c1yptoco- ccosis , pyogenic granuloma, keratoacanthoma, basal cell carcinoma) can mimic Molluscum contagiosum infection, consequently a biopsy is often necessa1y. MC infection is often accompaniecl by other viral infections, especially by papillomavirus. The usual method of treatment is curettage, but due to the bleecling that can be produced, the cryotherapy and, recently, the cydofovir are advisable. Scabies Scabies may be sexually transmitted and it is one of the most frequent skin disorclers to develop in HIV- infected patients. Scabies may have a number of different clinical manifestations in seropositive individuals, ranging from classic features to crusted (No1wegian) scabies in which a great number of mites are present and the itching is reduced. Scabies in HIV-infected patients may mimic psoriasis, atopic dermatitis, seborrheic dermatitis, lymphomatoid papulosis, and insect bite reactions. The cliagnosis is confirmed by examination of scrapings, which demon- strates mites and eggs. Treatment is usually similar to that used in immuno- competent hosts, though several applications of a sca- bicicle may be necessary. It is important that all partners shoulcl be treated simultaneously. Papular pruritic eruption (PPE) More ancl more frequently the PPE, an extremely pruritic dermatosis characterizecl by red or skin-colored, non-confluent micro-papules on a xerotic skin, invol- Acta Dermatoven APA Vol 10, 2001, No 1 Dermatoses in the AIDS ving wiclespread areas, most commonly the trunk, extre- mities and folcls, can be observed (Fig. 4). Clinically and histologically, PPE is similar to eosino- philic papulosis of Ofuji, ancl in the early stages can easily be confused with scabies (16). The classical therapies are systemic antihistamines, oral preclnisone, ancl topical corticosteroid preparations, but the treatment that seems to be more effective is the exposure to ultraviolet B phototherapy. Exceptional dermatoses The list in this group could be ve1y long, but we will name only the lesions that may be more significant to suspect the HIV infection. Psoriasis (P) There are scores of descriptions ranging from the transitional whitening with the first symptoms of HIV infection to appearance of the first outbreak after the infection in an inclividual who bas never before had a clinical disease. Nevertheless, nowadays the publica- tions about complicated psoriasis are more frequent in view of the intensity, frequency ancl extension of the outbreaks, or due to the associatecl symptoms like arthritis , e1ythroderma or invertecl psoriasis (17). The therapy depencls on the extension and the associatecl symptoms of the clisease. The existing hema- tic and hepatic changes limit the systemic treatment. The use of psoralen and ultraviolet A therapy is also effective. Oral hairy leukoplakia (OHL) This clinical manifestation is detected in about 2.5- 10% of cases, even though the incidence of this clisorder is clecreasing in HIV patients as a consequence of HAART (highly active anti-retroviral therapy) like other cutaneous manifestations of HIV infection. Most commonly, OHL is manifested as corrugated, whitish and asymptomatic plaques situatecl along the lateral borders of the tongue, rarely bilaterally. With the electron microscopy papilloma virus and Epstein-Barr virus have been detectecl in the lesion. The most practical treatment is the cryotherapy, though treatment is not always inclicatecl. Prurigo The etiology of the process is not fully known. The clinical and histopathologic findings may resemble classic prurigo nodularis founcl in immunocompetent hosts (Fig. 5). Nevertheless, prurigo seems to be a reaction pattern that may be associatecl with some bacte- 13 Dermatoses in the AIDS rial or vira! infections, especially in the anus area, secon- dary to HIV infection (18) (Fig. 6). Conclusion Treatment is mainly directed at suppressing the itching and avoiding secondary infections. Recently thalidomide bas been shown to be effective. It is the authors' suggestion that a solid knowledge of dermatology combined witl1 careful observation of symptoms and a thorough patient's history are important clues in detecting HIV positive persons. AUTHORS' ADDRESSES 1. Mathes BM, Douglas MC. Seborreic dermatitis in patients with the acquired immunodeficiency syndrome. J Am Acad Dermatol 1985; 13:947-951. 2. Muiioz Perez MA. Manifestaciones cutaneomucosas en pacientes VIH positivos: incidencia, correlaci6n clinica, inmunol6gica y dermatopatol6gica. Estudio prospectivo de 1161 pacientes. Actas Dermosifiliogr 1999; 90: 11-20. 3. Baradad M, Castel T, Iranzo P. Manifestaciones cutaneas del sida. Pie! 1987;2:392-409. 4. Jani er M, Reynaud B, Gerbaka J, Hakim C, Rabian C, M orel P. Signes cutanes de l'infection par le VIH: etude prospective de 267 patients. Ann Dermatol Venereol 1994; 121 (supl.1):46-47. 5. Valle SL. Dermatologic findings related to humano immunodeficiency virus infection in highrisk individual. J Am Acad Dermatol 1987; 17: 951-961. 6. Palacios S, Maldonado R, O Imos L. Enfermedades de Transmisi6n Sexual y Virus de la Inmunodeficiencia Humana.Rev.Ibero-Latinoamericana de E.T.S. 1989;3:412. 7. O Imos L. Condilomas acuminados (Verrugas genitales)I y II. Rev.Ibero-Latinoamericana de E.T.S 1990; 4: 73-81 and 131-142. 8. Smith KJ, Skelton HG, Yeager J. Cutaneous findings in HN-1-positive patients: a 42-month prospective study. J Am Acad Dermatol 1994; 31:746-754. 9. Moore PS, Chang I. Detection of herpesvirus-like DNA sequences in Kaposi 's sarcoma in patients with and those ,vithout HN infection. N Engl J Med 1995; 332: 1181-1185. 10. Coldiron BM, Bergstresser PR. Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus. Arch Dermatol 1989;125:357-361. 11. Haverkos HW, Friedman-Kien AE, Drotman DP et al. The changing incidence of Kaposi's sarcoma among patients with AIDS. J Am Acad Dermatol 1990; 22: 1250-1253. 12. O Imos L. Sifilis. In: Farreras/Rozman: Medicina Interna. Barcelona. Ed. DOYMA, S.A. 1992: 2312-2318. 13. Olmos L. Infecciones por Treponema. In: Diaz-Rubio/Espinos: Tratado de Medicina Interna. Madrid. Ed. PANAMERICANA 1994:1754-1759. 14. Belmar JM, Santidrian V, Ortega V, O Imos L. Leishmaniasis cutanea centrofacial infiltrada en sabana. Rev. Iberolatino-Amer ETS 1994; 8:211-216. 15. Ferrandiz C, Rib era M, Barranco JC, Clotet B,Lorenzo JC. Eosinophilic folliculitis in patients with acquired immunodeficiency syndrome. IntJ Dermatol 1992; 31:193-195. 16. Hevia O, Jimenez-Acosta F,Ceballos PI, Gould EW, Penneys NS. Pruritic papular eruption of the acquired immunodeficiency syndrome: a clinicopathologic study. J Am Acad Dermatol 1991; 24:231-235. 17. Obuch ML, Maurer TA, Becker B, Berger TG. Psoriasis and human immunodeficiencyvirus infection. J Am Acad Dermatol 1992; 27:667-673. 18. Raventos C, Borderas MA, Gonzalez C, Olmos L Infecci6n simultanea por 6 tipos de virus diferentes mas bacterias, hongos, dermatitis seborreica, dermatitis pruriginosa y Kaposi. Rev. Iberolatino-Amer ETS 1993; 7:177-179. Luis Olmos Acebes MD, Professor and Head oj the STD service, Servicio de Dermatologia, Hospital Universitario "San Carlos", Madrid, Spain Gonzalez Intxaurraga Maria Angeles MD, Glinica Dermatologica, Ospedale di Cattinara, Strada diFiume, 34149 Trieste, Italy Review 14 - ---------------- ---- ------------- Acta Dermatoven APA Vol 10, 2001, No 1