CUTANEOUS MANIFESTATIONS OF HIV Classification of dermatoses in HIV infection/AIDS:

1. INFECTIOUS DERMATOSES (a) VIRAL INFECTIONS

Acute exanthema of HIV disease HSV VZV EBV HPV CMV MC

(b) BACTERIAL INFECTIONS Staphylococcal infections Mycobacterial infections Bacillary angiomatosis Gingivitis Others ----- Pseudomonas, Salmonella, Nocardia, H. influenza, Rhodococcus, H. ducreyi, C. granulomatosis,

Chlamydia.(c) FUNGAL INFECTIONS

Dermatophytosis Candidiasis Other superficial mycosis ----- M. furor, trichisporicosis, alternariosis, curvularia spp. Deep infections ----- cryptococcosis, histoplasmosis, penicillinosis, sporotrichosis, blastomycosis, aspergillosis.

(d) PARASITIC INFECTIONS Scabies Demodicidosis Extrapulmonary pneumocystosis, leishmaniasis, cutaneous toxoplasmosis, acanthamoebiasis .

(e) STDs2. NON INFECTIOUS DERMATOSES

(a) Disorders of epidermal cell kinetics ------ Seborrhoeic dermatitis, Psoriasis, Reiter’s disease, Ichthyosiform dermatoses.

(b) Papular and follicular eruption of HIV

(c) Pigmentary changes

(d) Eczemas

(e) Cutaneous & systemic vasculitis of many etiologies has been reported to occur in HIV including ADR, CMV infection, PAN,

Lymphomatoid granulomatosis, Kawasaki’s disease and possibly HIV infection itself.

(f) ADR

(g) Neoplasm : KS, lymphoma, HPV induced cancers.

(h) Autoimmune and hyperimmune phenomenon

(i) Interface dermatitis

(j) Miscelleneous dermatoses

Insect bite reactions --- increased Erythroderma --- causes are drug reactions, atopic D, psoriasis, photosensitivity dermatitis, cutaneous T cell lymphoma,

Hypereosinophilic syndrome. P.rosea ---- with unusual fever and malaise. PRP PCT ---- in HIV disease, it is most often associated with underlying hepatopathy (HBV, HCV, alcoholism). Pseudoporphyria

can occur with drugs. Photosensitive eruptions Granuloma Annulare LP Eruptive dysplastic nevi Grover’s acantholytic dermatoses

(k) Nail and hair disorders.

ACUTE HIV INFECTION:Synonym: Acute retroviral syndrome/ primary HIV infection

The I.P. (from presumed exposure to development of acute febrile illness) ranges from 3-6 weeks (average = 14 days)varying with the route of infection and size of the viral inoculum. Commonly reported clinical manifestations include ------

fever fatigue rash myalgia arthralgia pharyngitis night sweats N/V/ Diarrhoea

Less common manifestations include ---------- decreased TC/platelet count, weight loss, aseptic meningitis, encephalitis, neuritis, myelitis, oral ulcers and/or genital ulcers. RESOLVES IN 2 WEEKS. The laboratory diagnosis of HIV-1 infection is made by 3 methods:

detection of p24 antigen detection of viral nucleic acids

viral culture.

BACTERIAL INFECTIONS:

Carraige rates in nares and perineum in ---------------- INCREASED Primary and secondary infections are common. Septicaemia can occur Primary infections include --------- FOLLICULITIS (MOST COMMON), BULLOUS IMPETIGO, ECTHYMA, FARUNCLES,

CARBUNCLES, CELLULITIS, BOTRYOMYCOSIS AND PYOSTOMATITIS. Secondary infection occurs in ATOPICS, EXCORIATIONS, HERPETIC ULCERS, KAPOSI’S SARCOMA, MOLLUSCUM

CONTAGIOSUM, SCABIES, INJECTION SITES TENDS TO BE RECURRENT. Management :

Ecthyma like lesions occur due to M. marinum Draining matted L.N with overlying erythema is caused by MAI. BCG vaccine may cause local and systemic infection in HIV patients.

The INCIDENCE OF MAC INFECTTIONS HAS FALLEN NOW A DAYS DUE TO PRIMARY PROPHYLAXIS WITH AZITHROMYCIN AND MORE RECENTLY HAART.

It causes a syndrome characterized by FEVER, BACTEREMIA AND RECURRENT AND/OR CHRONIC CELLULITIS (resembling erythema nodosum) in compromised. The organism is carried as bowel flora in 10% of homosexual men.

Treatment is difficult and prolonged. CLARITHROMYCN, CIPRO OR DOXYCYCLIN are the possible initial treatments.

Causes primary infection, secondary infection and bacteremia. Primary infection occurs as CELULITIS (i.e. ecthyma gangrenosum), infection at catheter sites. Secondary infection occurs over underlying dermatoses like Kaposi’s sarcoma.

Caused by Bartonella henselae and B. Quintana They occur in advanced immunosuppression. CHARACTERIZED BY ANGIOPROLIFERATIVE LESIONS RESEMBLING CHERRY ANGIOMAS, PYOGENIC GRANULOMAS OR

KAPOSI’S SARCOMA.

1. Staph. Aureus is the most common bacterial pathogen in AIDS.

Treat the infection Eradication of underlying dermatoses Eradication of nasal carriage with mupirocin oint Chronic oral prophylaxis for recurrent infection

2. Atypical mycobacterial infection occurs more in HIV infected patients and cause cutaneous lesions. The most common of these are the MAI complex.

5. BACILLARY ANGIOMATOSIS AND BACILLARY PELIOSIS:

4. PSEUDOMONAS AERUGINOSA

3. HELICOBACTER CINEADI

A DELAY OF 3-4 WEEKS EXISTS BETWEEN NEWLY ACQUIRED HIV-1 INFECTION AND DEVELOPMENT OF ANTIBODIES ---- CALLED WINDOW PERIOD

CLINICALLY LESIONS ARE RED TO VIOLACEOUS DOME SHAPED PAPULES, NODULES OR PLAQUES RANGING IN SIZE FROM FEW MILLIMETER TO UPTO 2-3 CM IN DIAMETER. They are soft to firm and may be tender on palpation.

The number of lesions ranges from solitary lesions to more than 100. Nearly any skin site may be affected but tends to spare the palms, soles and mucosa. Spectrum of internal disease includes---- soft tissue masses, bone marrow, lymphadenopathy, splenomegaly and

hepatomegaly. Course is variable ----- some regress spontaneously, others with treatment and others spread through blood and

lymphatics to internal organs. Treatment: erythromycin 250-500 mg PO qid or doxy 100 mg bd till lesions resolve ------ usually 3-4 weeks. As with all other OIs in HIV, they may recur.

FUNGAL INFECTIONS: Cutaneous fungal infections in HIV infection occur as

Superficial infections Invasive cutaneous infections or Systemic infections with hematogenous dissemination to the skin.

One third of HIV patients have superficial infections with ringworm. May be >Typical Extensive Altered morphology due to enhancement or diminution of inflammatory component. Involvement of soles to give rise to diffuse hyperkeratosis or keratoderma blenorrhagica like picture Proximal subungual onychomycosis is the CHARACTERISTIC NAIL INVOLVEMENT IN HIV. Other types of nail involvement

can also occur. Relapses are common.

Cutaneous candida infections of intertriginous areas and moist keratinized cutaneous sites like anogenital area are relatively uncommon in AIDS. Occur with equal frequency in AIDS and NON AIDS individuals.

Candidial colonization of the oropharynx is common in HIV even in the absence of clinical findings. C. albicans is the main pathogen. Non albicans species are found in ADVANCED HIV INFECTION WITH VERY LOW CD4 CELL COUNT.

ESOPHAGEAL CANDIDIASIS, an AIDS defining condition, occurs only in advanced immunosuppression (CD4 count < 100 cells/microlitre).

Disseminated candidiasis is uncommon in HIV because of B cell activation and the presence of anti candidial protective antibody.

Vaginal candidiasis is commoner in HIV infected females. Children with HIV infection commonly experience candidiasis in the diaper area and intertrigo in the axilla and neck folds.

Fingernail chronic candida paronychia with secondary nail dystrophy (onychia) also is common in HIV infected children.

Invasive fungal infections arise by local invasion of the skin and mucosa often followed by lymphatic or hematogenous dissemination to viscera or skin or more commonly, activation of latent pulmonary focus of infection. Eg. CRYPOTOCOCCOSIS, HISTOPLASMOSIS, COCCIDIODOMYCOSIS, SPOROTRICHOSIS OR PENICILLINOSIS. Cutaneous lesions are mostly MC like on face and trunk.

VIRAL INFECTIONS: The incidence of viral OIs has decreased after the institution of HAART except the manifestations of HPV.

1. HSV: With more advanced immunosuppression, lesions tend to be SUBACUTE OR CHRONIC INDOLENT. ATYPICAL RESPONDING LESS PROMPTLY TO TREATMENT

With increasing immunosuppression, recurrent HSV infection may become persistent and progressive. Erosions occurring in typical sites (perioral, anogenital and digital) enlarge and deepen into painful ulcers. In addition to ulceration, chronic HSV may present as proliferative lesions of the epidermis with or without scales. ACYCLOVIR 200 mg 5 times daily is effective in acute episode and in recurring cases should be used continuously as 200 – 400 mg daily. In resistant cases, i.v. FOSCARNET /CIDOFOVIR can be used.

2. VZV:

RINGWORM INFECTIONS:

MUCOCUTANEOUS CANDIDIASIS:

Oropharyngeal candidiasis is a marker of disease progression.

INVASIVE FUNGAL INFECTIONS:

Viruses are major pathogens causing OIs in HIV disease many of which are manifested at the mucocutaneous sites.

Chronic herpetic ulceration of >1 months duration, is a AIDS defining criteria

In a compromised host, can present as ----- SEVERE VARICELLA PERSISTENT VARICELLA DERMATOMAL HERPES ZOSTER DISSEMINATED HZ ---- defined as cutaneous involvement greater than 3 contiguous dermatomes, more than 20 lesions

scattered outside the initial dermatome or systemic infection (hepatitis, pneumonitis, encephalitis. CHRONIC OR RECURRENT HZ.

3. MC The clinical course of MCV infection in HIV disease differs significantly from that in the normal host and is an excellent clinical marker of the degree of immunosuppression.

Progressive & Recurrent after treatment unless the

immune status improves with HAART. Large numbers Gaint MC Extensive molluscum of more than one anatomic region (eg. face & groin) is highly suggestive of a CD4 count less than

50/c.mm.

4. HPV Infections by HPV occur commonly during the course of HIV disease and their occurrence is NOT INFLUENCED BY HAART. Intraepithelial carcinomas can develop even without the usual HPV types A/W malignancy.

Common warts: Become numerous, confluent Refractory to usual treatment modalities. Precancerous lesions identical to mucosal lesions (SIL & SCCIS) can occur periungually and on the nail bed epidermis

(usually fingers) and may progress to invasive SCC.

Genital warts: HPV 6 and 11 cause genital warts whereas HPV 16 and 18 cause precancerous lesions, low grade SIL, high grade SIL and invasive SCC. Oral warts: Resemble genital warts. Extensive intraoral condyloma acuminata (oral florid papillomatosis) presents as multiple large plaques that can transform to verrucous carcinoma.

HPV induced dysplasia: LSIL, HSIL, Invasive SCC. The most common sites are CERVIX, ANUS, PERINEUM, VULVA, PENIS, OROPHARYX/TONGUE, CONJUNCTIVA AND NAIL APPARATUS.

Management of external anogenital HPV infection is directed at identifying these dysplasia and SCC. All HIV infected individuals should be examined annually for evidence of HPV infection, especially those with prior HPV infection. Cervix and anal canal must also be seen. If SIL is found, examination should be more frequent --------- 4-6 monthly. Biopsy is indicated. For minimally invasive SCC in anal verge or on external anogenital sites, surgical excision is needed with adequate borders around the lesion. Invasive SCC of the anus is treated by radiation therapy and chemotherapy is given.

PARASITIC INFECTIONS:

In individuals with advanced immunosuppression, scabies can occur with minimal or no pruritus but an

extensive papulosquamous eruption, i.e. hyperkeratotic crusted scabies or Norwegian scabies. Secondary Staph aureus infection can occur rarely complicated by bacteremia.

Oral ivermectin (200 microgram/kg weekly) is the most effective therapy.

Causes itchy papular lesions in HIV patients. Affected areas are the head, neck, trunk and arms.

Scrapings show numerous mites. It rapidly relapses with gamma benzene hexachloride.

It is a rare form of encephalitis that may occur in immunocompetant and immunosuppressed hosts. It may occur in ADVANCED AIDS (CD4 T cell count< 50/c.mm). In AIDS patients, skin lesions are the most common presentation (75% cases). Lesions occur as deep seated nodules that suppurate, crust or weep serosanguinous fluid occurring mostly in extremities. Sinusitis is commonly present and the palate or nasal septum may be perforated. The diagnosis is based on the biopsy of the ulcer which will show suppurative and granulomatous inflammation WITH VASCULITIS. The vasculitis is uncommon in other infectious granulomas and should alert the pathologists to search acanthamoeba.

STDs:

OPORTUNISTIC NEOPLASMS: The prevalence of ONs including KS, HPV induced neoplasia, undifferentiated non Hodgkin’s B cell lymphoma (NHL) and primary CNS lymphoma is increased in HIV disease. The incidence of melanoma and non melanoma skin cancer, Merkel cell carcinoma, HL, T cell lymphomas and seminoma also may be increased. Many of these OIs are associated with oncogenic human viruses and diminished immune surveillance.

WIDESPREAD infection of face is common and highly characteristic of HIV.

1. Scabies:

2. Demodicidosis:

3. Acanthamebiasis

SEE NOTES ON KAPOSI SARCOMA

PAPULOSQUAMOUS DISORDERS:

3 dermatologic disorders characterized by scaling patches and plaques are seen in HIV infected persons: SEBORRHOEIC DERMATITIS, PSORIASIS AND REITER’S DISEASE.

It is one of the commonest skin changes in HIV infection associated with overgrowth of or abnormal reactivity to Pityrosporum yeasts.

Initially they are morphologically typical but later on they become

WIDESPREAD ATYPICAL --------- nummular eczematous. HISTOLOGICALLY, there is keratinocyte necrosis and inflammatory obliterative changes at the DEJ.

The prevalence of psoriasis and psoriatic arthritis is increased in AIDS. Psoriasis may have its onset before or after HIV. Preexisting psoriasis may flare up after HIV infection ---- widespread guttate, erythroderma, pustular, extensive plaque

type. Psoriasis developing after HIV may start at atypical sites like flexural.

: see notes.

PRURITUS AND PRURITIC ERUPTIONS OF HIV DISEASE:

Pruritus is a common complaint in patients with late symptomatic and advanced HIV disease occurring commonly in patients with CD4 counts of less than 50 cells per microlitre compared to those of counts > 250 cells per microlitre.

Causes are:1. Eosinophilic folliculitis2. ADR3. Atopic dermatitis (flares in AIDS)4. XEROSIS5. Urticaria6. Scabies7. Insect bites8. Demodicidosis9. Allergic contact dermatitis.10. Lymphoma11. Renal faiure12. Viral hepatitis13. Obstructive liver disease.

It is the most common non staphylococcal folliculitis in HIV infected persons. It occurs in patients with CD4 T cell counts less than 200/c.mm.

Characteristically is a chronic, waxing and waning eruption with moderate to severe pruritus. The etiology and pathogenesis is unknown but may be associated with a th2 response to unknown antigen.

Secondary changes include ---- excoriations, excoriated papules, LSC and prurigo nodularis as well as secondary S. aureus infection.

1. Kaposi’s sarcoma in AIDS:

1. Seborrhoeic eczema and seborrhoeic folliculitis:

It is one of the early signs of immunosuppression and is seen in over 50% AIDS patients.

2. Psoriasis

3. Reiter’s disease

Eosinophilic folliculitis:

Lesions are in the form of pink to red edematous folliculocentric papules that occur symmetrically above the nipple line.

The most effective treatment for EF is prednisolone starting with 70 mg PO and tapered at weekly intervals by 5-10 mg. Other drugs are ----

Isotretinoin PUVA Topical tacrolimus. Sedating antihistaminics.

DISORDERS OF THE OROPHARYNX: Nearly all HIV infected individuals experience disorders of the oropharynx during the course of the disease. They include:

Candidiasis Herpetic ulcers Xerostomia Exfoliative cheilitis Oral hairy leukoplakia ------------- SEE NOTES. Kaposi’s sarcoma, non Hodgkin’s lymphoma, HPV induced SCC. Patchy depallilation of tongue Ulcers of uncertain cause.

ADVERSE CUTANEOUS DRUG ERUPTIONS: The incidence of adverse cutaneous drug reactions is high in HIV disease (100 times more common than in general population). This is increased with advancing immunosuppression. The commonest agents are SULFONAMIDES AND PENICILLIN. ECZEMATOUS/MORBILLIFORM eruptions were by far the commonest variety. Others are EM, LICHENOID, URTICARIA, FDE, SJS, TEN. Systemic manifestations occur in some as fever, headache, myalgia and arthralgia.

Antiretroviral agents: ART has significant incidence of ADR including -------- Hypersensitivity reactions ---- with

NNRTI Abacavir Amprenavir

Approximately half of these cases resolve despite continuation of therapy. Drug therapy should be discontinued if the following occur:

Mucosal involvement Blistering Exfoliation Clinically significant hepatic dysfunction Fever greater than 39 degree C Intolerable fever or pruritus.

Lipodystrophy syndrome ---- with PIs. Discontinuation or replacement of PI therapy does not result in reversal of dysmorphic changes in most patients.

Drug interactions: mainly with PIs. Pigmentation: Zidovudine treated individuals experience longitudinal melanonychia with brown black longitudinal streaks

in the nail plate. The pigmentary changes are usually noted in the finger and / or toe nails within 4-8 weeks after initiation of ZVD therapy. Pigmentation also occurs in the mucous membranes. Diffuse hyperpigmentation mimicking primary adrenal insufficiency has been reported.

Other ZVD ADRs include ------- hypertrichosis, hypersensitivity, leucocytoclastic vasculitis and paronychia. Zalcitabine can cause apthous like ulceration of the oropharynx and esophagus.

INTERFACE DERMATITIS: A histological entity showing basal keratinocyte vacuolation and necrosis and dense inflammatory infiltrate in the DEJ appears to be specific to HIV. Such changes may be superimposed on well recognized conditions like seborrhoeic eczema and psoriasis occurring in AIDS.

AUTOIMMUNE AND HYPERIMMUNE PHENOMENON: Thromocytopenic purpura is the most recognized AI disease seen in AIDS. Bleeding from the gums, nose, rectum and semen can occur. Dangerous hemorrhage is however rare. Prednisolone 1 mg/kg/day helps but seldom indicated. Others include:

Vitiligo Sicca syndrome Pemphigoid Low titre ANA Atopic disease

HAIR DISORDERS: Diffuse alopecia. Telogen effluvium. Alopecia areata. Vertical thinning. Fungal Scalp disease. Localized loss around scalp margin. Hair loss From Syphilis. Premature graying.

NAIL DISORDERS: Beau’s lines Pallor of nail beds Yellow nail syndrome --------- this occurs mainly in A/W pneumocyctis pneumonia.

Skin biopsy reveals inflammation containing eosinophils surrounding and involving the hair follicle.Peripheral eosinophilia is common.