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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) STDs
2. 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.

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

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

 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 :

• 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.


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.

3. HELICOBACTER CINEADI

 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.

4. PSEUDOMONAS AERUGINOSA

 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.

5. BACILLARY ANGIOMATOSIS AND BACILLARY PELIOSIS:

 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.
 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.

RINGWORM INFECTIONS:

Onethird 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.

MUCOCUTANEOUS CANDIDIASIS:

 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.

Oropharyngeal candidiasis is a marker of disease progression.

 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:


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.

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

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

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


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

1. Scab
ies:
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.

2. Demodicid
osis: 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.

3. Acanthameb
iasis
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.

SEE NOTES ON KAPOSI SARCOMA


1. Kaposi’s sarcoma in AIDS:

PAPULOSQUAMOUS DISORDERS:

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

1. Seborrhoeic eczema and seborrhoeic


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

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

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.

2. Psoriasis

 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.
3. Reiter’s disease

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 folliculitis
2. ADR
3. Atopic dermatitis (flares in AIDS)
4. XEROSIS
5. Urticaria
6. Scabies
7. Insect bites
8. Demodicidosis
9. Allergic contact dermatitis.
10. Lymphoma
11. Renal faiure
12. Viral hepatitis
13. Obstructive liver disease.

Eosinophilic folliculitis:
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.

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

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

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

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.