HIVAND ITS

CUTANEOUS
MANIFESTATIONS

Alexander Adam Su
Nur Shalina
Fatima Zahra
 INTRODUCTION
● Human Immunodeficiency Virus (HIV) is a retrovirus infection which causes an acquired immunodeficiency
of the host via reduction in the number of CD4 T cells.

● Skin conditions has affected approximately 90% of all HIV patients.

HIV Type 1
Types
HIV Type 2

Pathophysiology of skin conditions caused by HIV:

⮚ Immunodeficiency associated with HIV increased risk of infection and malignancy

⮚ High reaction rate and increased photosensitivity risk from antiretroviral medication.
Types of skin diseases found in HIV
Infection

Malignancy

Inflammatory

Miscellaneous
 Infection
Bacterial Infection
● Streptococcal and Staphylococcal infection

Cellulitis Ecthyma Impetigo Folliculitis

● Syphilis may present as:

○ Primary : painless chancre in genital region
○ Secondary: Widespread rash with systemic symptoms
Chancre
Viral Infection

● Herpes simplex virus (HSV) is the most common viral infection noted in HIV and is often severe
and recurrent. Manifests as small groups of painful vesicles. Oral herpes

● Varicella zoster virus infection (shingles) can cause a painful vesicular rash, typically in a
dermatomal distribution or as a disseminated rash due to the immunosuppression

● Molluscum contagiosum infection is caused by a poxvirus, resulting in small, round, skin-coloured

papules. Genital herpes

● Human papillomavirus (HPV) often persist despite highly active antiretroviral therapy (HAART)

○ Genital wart

○ Malignancy

● Oral hairy leukoplakia - Eipstein Barr virus. Typically only at CD4 counts below 200–
Molluscum contagiosum
300micromol/L.
Fungal Infection
● Common presentations:
Tinea corporis
○ Tinea
○ Onychomycoses
○ Candida
● Malassezia yeast: Pityrosporum folliculitis and pityriasis versicolor
● Systemic mycoses
Onychomycoses

Pityrosporum folliculitis pityriasis versicolor

Candidiasis
Parasitic Infection
● Leishmaniasis
● Strongyloidiasis
● Acanthamebiasis
Malignancy
● Kaposi sarcoma caused by HHV 8. This is the most prevalent
malignancy related to HIV. Psoriasis
● Squamous cell carcinoma and basal cell carcinoma.
● Lymphoma:
○ Mycosis fungoides
○ Anaplastic large cell lymphoma
○ Plasmablastic lymphoma.
Seborrheic dermatitis

Inflammatory
● Psoriasis, seborrheic dermatitis, and eczema – common
● Pruritic papular eruption can often be the first presentation of HIV in an
otherwise asymptomatic person. Eczema
● Eosinophilic folliculitis typically only occurs at CD4 counts of <300
Miscellaneous

1. Adverse drug reaction:

3. Lipodystrophy is caused by loss of
o Morbilliform eruption
fat under the skin.
o Steven-Johnson syndrome
4. Other conditions:
o Toxic epidermal necrolysis
○ Ichthyosis
o Drug Rash with Eosinophilia and Systemic Symptoms
○ Aphthous ulcers
(DRESS)
○ Cutaneous vasculitis
2. Photosensitivity reaction:
○ Blue nails.
❖Porphyria cutanea tarda

❖chronic actinic dermatitis

Acute HIV Syndrome
● Acute human immunodeficiency virus infection syndrome refers to symptoms experienced by many
people at the time of initial infection with human immunodeficiency virus (HIV).
● It is also known as acute retroviral syndrome.
● Acute HIV infection syndrome is classified according to general, neurologic, and dermatological
manifestations.
● Symptoms are non-specific.

• Develops within 2 to 4 weeks

after infection with HIV
• Level of HIV in blood is high
• Risk of transmission is high
 General Neurologic Dermatological

▪ Fever – Most common ▪ Meningitis ▪ Erythematous maculopapular rash

▪ Sore throat ▪ Encephalitis o Symmetrical
▪ Swollen lymph nodes ▪ Peripheral neuropathy o Involves face, palms and soles as well
▪ Headache/pain behind the eyes ▪ Myelopathy as trunk and limbs.
▪ Sore muscles and joints
▪ Malaise
▪ Loss of appetite, with or without
weight loss
▪ Gastrointestinal tract symptoms: ▪ Mucocutaneous ulceration
nausea, vomiting, diarrhoea
 Eosinophilic Pustular Folliculitis in HIV
● Eosinophilic pustular folliculitis is a recurrent skin disorder of unknown cause.
● It is also known as eosinophilic folliculitis and Ofuji disease.
● Variants:
○ Classic
○ Immunosuppression / HIV associated
○ Infantile
○ Malignancy type
○ Medication-associated or drug- induced
● Clinical features:
○ Itchy red or skin-coloured dome-shaped papules and pustules.
○ Site: face, scalp, neck and trunk

● Longstanding cases may develop dermatitis or a form of prurigo due to itchiness and scratching.
Pruritic Papular Eruption of HIV
● Papular pruritic eruption is one of the most common skin conditions associated with HIV disease in
tropical and subtropical regions.

● It is classified as WHO Stage 2 HIV disease. It is reported to be a skin sign of advanced HIV, being
three times more common when the CD4 lymphocyte count is less than 200 x10 9/L.

● No clear pathophysiology but medications, autoimmunity, and direct HIV infection of the skin have
been considered but not proven.

● Hypersensitivity to arthropod bites and a form of chronic recall reaction to arthropod antigens in the
setting of HIV-associated immune dysregulation has been suggested.
Clinical features:
1. Chronic rash
○ Small, red, intensely itchy, firm papules
○ Evolve into hyperpigmented macules and nodules
○ Site: most common on exposed skin (extremities)
 Photosensitivity in HIV disease

● Idiopathic photosensitivity may be the presenting complaint of advanced HIV

disease.
● Photosensitive eruptions present with two distinct morphologies:
❖ photodistributed lichenoid eruptions
❖ photodistributed eczematous eruptions. cART and other drugs cause photosensitive
eruptions.
● Risk factors for photosensitivity include African ethnicity and cART.
● Photosensitivity occurs in association with other diseases such as porphyria cutanea
tarda, chronic actinic dermatitis, lichenoid photcr eruption, and photosensitive
granuloma.
Lichenoid photosensitive eruption

A 45-year-old African female with

advanced HIV disease. Violaceous
hyperpigmented plaques in sun-
exposed sites on the face.
Depigmentation has occurred within a
plaque on the forehead. Other than
HIV disease, neither underlying
systemic disease nor drug exposure
were identified.
 Oral hairy
leukoplakia

Etiology
- OHL emerges from latency In advanced HIV disease and causes benign mucosal
hyperplasia.
- Occurs with CD4+ cell count <300/IJL.
Clinical Manifestation
- Asymptomatic:, but stigmatization of HIV disease.
- White or grayish-white, well-demarcated plaques with corrugated texture.
- Most commonly on the lateral and Inferior surfaces of the tongue. Often present
bilaterally.
- Oropharyngeal candidiasis often present as well.
Differential Diagnosis
- Pseudomembranous candidiasis (thrush)
- geographic or migratory glossitis
- tobacco-associated leukoplakia
- mucous patch of secondary syphilis
- SCCIS
Diagnosis: Clinical diagnosis
- Lesions do not rub off; does not clear with
adequate anticandidal therapy.
Course: Usually resolves with cART and immune
restoration. Recurs when cART failing.
Treatment: Podophyllin 25% in tincture of benzoin
applied to the lesion with a cotton tipped applicator
for 5 minutes. Effective cART results in regression and
clearing of OHL
Adverse cutaneous drug eruptions (ACDEs) in
HIV disease
● Incidence is 100 times more common In persons with HIV disease compared to
that in the general population, becoming more frequent with advancing
immunodeficiency.
● Exanthematous or morbilliform eruptions are the most common
manifestation.
● Other morphologies such as urticaria, erythema multlforme major, erythema
multlforme minor, toxic epidermal necrolysis, lichenoid eruptions, vasculitis,
and fixed drug eruptions also occur.
● Twenty percent of persons report systemic symptoms (fever, headache,
myalgias, and arthralgias).
● cART can cause a wide spectrum of ACDE
Etiology
- Most common drugs causing ACDE in HIV disease are aminopenicillins and sulfa
drugs.
Factors associated with increased risk of drug eruptions include:
- female gender
- CD4+ T cell count <200/𝜇L
- CDS+ T cell count >460/𝜇L
- history of prior drug eruptions
Treatment
● Short-term oral corticosteroid therapy may be effective in reducing the risk of
adverse drug eruptions.
● Adverse Effects of Antiretroviral Therapy, Six classes of antiretroviral medications
are currently in use:
- Non-nucleoside reverse transcriptase inhibitors (NNRTis)
- Protease inhibitors
- NRTis
- Integrase inhibitors
- Chemokine receptor 5 antagonists
- Entry inhibitors
These medications are associated with a variety of cutaneous adverse effects,
including hypersensitivity reactions, lipodystrophy, retinoid-like effects,
hyperplgmentation, nail changes, and injection site reactions
 Lipodystrophy
● HIV disease-related lipodystrophy is characterized by abnormal fat
distribution with lipohypertrophy, lipoatrophy, or both.
● Abnormal fat distribution is often accompanied by metabolic
abnormalities, ie., elevation of fasting glucose and insulin levels,
hypertriglyceridemia, hypercholesterolemia, and decreased high-
density lipoprotein.
Clinical manifestation
Lipohypertrophy presents with central obesity, cushingoid habitus ("buffalo
hump"), increased neck girth (Fig. 27-67), increased abdominal girth caused
by intraabdominal fat ("protease pouch" or •cnx belly")
and breast enlargement Facial lipoatrophy, most pronounced on the cheeks
and temples, is striking and stigmatizing for HIV disease (Fig. 27-68). Treatment of lipodystrophy
Substitution of regimens containing
stavudine and zidovudine has been
shown to be of partial benefit for
lipoatrophy. Facial lipoatrophy has
been treated with soft tissue fillers
Management of HIV
& its cutaneous
manifestation
 Eosinophilic Folliculitis
Diagnosis
● Based on the finding of intensely pruritic perifollicular lesions.
● Difficult to distinguish from bacterial folliculitis and pruritic papular eruption.
● Lesional biopsy: an inflammatory infiltrate of lymphocytes and eosinophils at the level of the
isthmus & sebaceous gland.

Treatment
● Begins with the initiation of HAART to reconstitute the immune system.
○ Initially worsen after starting HAART due to immune reconstitution inflammatory syndrome.
● Topical corticosteroids & oral antihistamines can alleviate the itching & decrease the size and
number of lesions.
○ A short tapered course of prednisone gives immediate relief of symptoms, e.g. 70 mg
tapering by 5 or 10 mg daily.
● Treatment with the antifungal drug itraconazole, the antibiotic metronidazole, and the anti-mite
drug permethrin may lead to some improvement of symptoms.
● Other therapies include PUVA, topical tacrolimus, & isotretinoin.
 Adverse Cutaneous Drug Eruptions
Diagnosis
● Careful, complete patient history and also exclusion of other likely causes for rash (e.g.
infectious, immunologic, allergic, and contact).
● Biopsy for excluding other etiologies for the rash.

Treatment
● Clinically stable patients with mild rash and an absence of systemic symptoms can often be
managed with antihistamines.
● More severe symptoms require:
○ discontinuation of the drug and preclude reintroduction.
○ patients may require corticosteroids and possibly hospitalization.
○ referral to a dermatologist may be helpful.
 Variations in Common Mucocutaneous
Disorders in HIV Disease

● Kaposi sarcoma ● Staphylococcus aureus infection

● Nonmelanoma skin cancer ● Human papillomavirus infection

● Aphthous ulcer ● Herpes simplex

● Dermatophytosis ● Disseminated fungal infection

● Syphilis ● Mucosal candidiasis

● Molluscum contagiosum ● Varicella-Zoster virus infection

 Staphylococcus aureus infection

● S. aureus is the most common cutaneous bacterial pathogen in the general population and in HIV disease.

● The nasal carriage rate of S. aureus is up to 50%, which is twice that of HIV-seronegative control groups.

● In most instances, S. aureus infections are typical, presenting as

○ primary infections (folliculitis, furuncles, or carbuncles),
○ secondarily infections (excoriations, eczema, scabies, herpetic ulcer, or KS),
○ cellulitis, or
○ venous access device infections,

● All of which can be complicated by bacteremia & disseminated infection.

● Methicillin-resistant S. aureus (MRSA) infections, if not identified, may be more severe because of delay in
initiation of effective anti-MRSA therapy
 Staphylococcus aureus infection
Diagnosis
● Culture of a clinical sample with use of a polymerase chain reaction probe.
● Rapid culture techniques are also available.
● Antimicrobial susceptibility testing should be performed on MRSA isolates.

Treatment
● Incision and drainage of the abscess, and some patients will improve with local therapy alone.
● Addition of antibiotics with the following conditions:
○ severe or extensive disease or rapid progression in the setting of associated cellulitis.
○ associated comorbidities or immunosuppression.
○ extremes of age.
○ in the case of difficult-to-drain abscesses or lack of response to incision and drainage.
○ oral antibiotic therapy includes trimethoprim- sulfamethoxazole (1-2 double-strength
tablets twice daily), doxycycline (100 mg twice daily), clindamycin (300 to 450 mg four
times daily), and linezolid (600 mg twice daily).
● Duration of antibiotic treatment is typically 5 to 10 days but should be guided by the severity
of the infection and by clinical response to therapy.
Kaposi’s sarcoma
● A low-grade vascular tumor associated with human
herpesvirus 8 infection (HHV8).

● Predominantly a cutaneous malignancy, KS is a locally

aggressive endothelial tumor belonging to the family of
vascular sarcoma.

● KS lesions may be confused with other vascular

lesions, such as angiomas & pyogenic granulomas.
Kaposi sarcoma

Diagnosis
● KS may be suspected from the appearance of lesions and the patient's risk factors

● A definite diagnosis can be made only by biopsy and microscopic examination.

● Detection of the KSHV protein LANA in tumor cells confirms the diagnosis.
Non melanoma skin cancer
Aphthous ulcers

● Recurrent aphthous ulcers occur more frequently, become larger (often> 1 cm), and/or become
chronic with advanced HIV disease.

● Ulcers may extensive and/or multiple; commonly involving tongue, gingiva, lips, &
esophagus, causing severe odynophagia with rapid weight loss.

Treatment:
- Intralesional triamcinolone.
- Prednisone 70 mg tapered by 10 or 5 mg per day over 7 or 14 days.
- In resistant cases, thalidomide is an effective agent.
Dermatophytosis
● Dermatophytosis: a superficial fungal infection of keratinized tissues like skin, hair, & nails, manifesting as an opportunistic
infection
● Most commonly due to Trichophytum rubrum, frequently causing tinea cruris, corporis & onychomycosis.
● Epidermal dermatophytosis can be extensive, recurrent, & difficult to eradicate.
○ Multiple fluctuant erythematous ulcerative nodules
● Proximal subungual onychomycosis occurs in advanced HIV ds
○ Chalky-white discoloration of the undersurface of
proximal nail plate
○ An indication for HIV serotesting
Syphilis (Malignant syphilis / lues
maligna)

Multiple skin lesions of lues maligna in an

HIV-infected patient: A) papulopustular
lesions and necrotic ulcers over the face; B
and C) trunk; D and E) extremities.
Molluscum contagiosum
● In advanced HIV disease, molluscum contagiosum has up to 18% prevalence;

● The severity is a marker for advanced immunodeficiency.

● Patients may have multiple small papules or nodules or large tumors > 1 cm in diameter, most commonly arising on the face,
especially the beard area, the neck, and intertriginous sites.

● Cyst-like mollusca occur on the ear.

● Occasionally. mollusca can arise on the non-hair-bearing skin of the palms/soles

 Molluscum Contagiosum
Diagnosis
● Primarily based on clinical appearance but can be confirmed with skin biopsy; histologic
examination using hematoxylin and eosin staining characteristically reveals keratinocytes
with eosinophilic intracytoplasmic inclusion bodies called molluscum bodies (or Henderson-
Patterson bodies).

Treatment
● Antiretroviral therapy is the mainstay of
treatment for in persons with HIV.
● If the lesions persist despite the use of
antiretroviral therapy, localized treatments can
be used, including cryotherapy, curettage, pulsed
dye laser therapy, and immune modulators, such
as topical imiquimod.
Human Papilloma Virus
● With advancing immunodeficiency, cutaneous and/or mucosal warts can become extensive & refractory to treatment.

● HPV-induced intraepithelial neoplasia, termed squamous intraepithelial lesion (SIL), is a precursor to invasive SCC arising most
often on the cervix, vulva, penis, perineum & anus.

● In females with HIV disease, the incidence of cervical SIL is 6 -8 x that of controls.

● SIL on the external genitalia, perineum or anus is best managed with local
therapies such as imiquimod cream, cryosurgery, electrosurgery or laser surgery
rather than with aggressive surgical excision
 Herpes Simplex
● HSV-1 or 2 infection is common opportunistic infections of HIV disease.

● Most reactivation is subclinical.

● Anogenital reactivation is particularly frequent.

● With advancing HIV disease, early lesions present with erosions or

ulcerations associated with epidermal necrosis without vesicle formation.

● Untreated, these lesions may evolve to large, painful ulcers with

rolled margins in the oropharynx, esophagus, and anogenitalia
 Herpes Simplex
Treatment
● Oral valacyclovir, famciclovir, or acyclovir for 5 to 10 days.
● Intravenous acyclovir may be required for severe
mucocutaneous disease and/or disseminated disease.
● Persons with HIV may opt for episodic treatment or daily
suppressive therapy.
● Primary prophylaxis for herpes simplex is not
recommended, regardless of HIV serostatus.
Guidelines for the Prevention and Treatment of Opportunistic Infections
in Adults and Adolescents with HIV
Disseminated Fungal Infection
● Latent pulmonary fungal infections with Cryptococcus neoformans,
Coccidioides immitis, Histoplasma capsulatum, and Penicillium marneffei
can be reactivated in HIV disease & disseminated to the skin & other organs.

● The most common cutaneous presentation of disseminated infection is

molluscum contagiosum-like lesions on the face;

● Other lesions such as nodules, pustules, ulcers, abscesses, or a papulosquamous eruption resembling guttate psoriasis (seen with
histoplasmosis) also occur

(A) Numerous ulcerating nodular skin lesions (black arrows).

(B–C) Verruciform scaly skin nodules in the lateral left eyelid &
anterior to the left ear (white arrows).
Mucosal Candidiasis
● Mucosal candidiasis affects the upper aerodigestive tracts and/or vulvovagina in HIV disease.

● Initial HIV manifestation: oropharyngeal candidiasis (most common) - also a marker for disease progression

● Advanced HIV disease: esophageal & tracheobronchial candidiasis - AIDS-defining conditions.

● The incidence of cutaneous candidiasis may be increased; with insulin resistance associated with cART, balanoposthitis can be seen.

● In young children, chronic candida paronychia and nail dystrophy occur

Candida vulvovaginitis: Erythema and excoriations of

the vulva. Note the satellite lesions near the borders of
the inflamed areas
Varicella-Zoster Virus (VZV) Infection
● Primary VZV infection (varicella or chicken pox) in HIV disease can be severe, prolonged, and complicated by visceral VZV
infection, bacterial secondary infection, and death.

● HZ occurs in 25% of persons during the course of HIV disease, associated with modest decline in immune function.

● Cutaneous dissemination of HZ is relatively common.

● However, visceral involvement is rare.

● With increasing immunodeficiency, VZV infection can present clinically as chronic dermatomal verrucous lesions; one or more
chronic painful ulcers or erythematous lesions within a dermatome; crusted erosions, ulcer, or nodule.

Grouped vesicular lesions on erythematous base in Necrotic and ulcerative lesions inpatient Crusted grouped lesions of multidermatomal
patient with Herpes zoster. with Herpes zoster involvement in Herpes zoster patient.
Varicella-Zoster Virus (VZV) Infection

● Untreated, these lesions persist for months.

● HZ can recur within the same dermatome(s) or in other dermatomes.

● VZV can infect the CNS causing a rapidly progressive chorioretinitis with acute retinal necrosis, chronic encephalitis, myelitis,
radiculitis, or meningitis.

● Extensive HZ may heal with hypertrophic or keloidal scar

Multidermatomal involvement before treatment in a

Healed Herpes zoster in the same patient
HIV infected patient
 Varicella-Zoster Virus
Diagnosis
● Based on a characteristic clinical presentation.
● Confirmed by obtaining a swab of a fresh lesion and testing with polymerase chain reaction,
direct fluorescent antibody (DFA), or culture.

Treatment
● Uncomplicated Cutaneous Zoster: oral therapy with either valacyclovir or famciclovir 3 times
daily dosing.
● Severe or Disseminated Zoster: intravenous acyclovir may be required.
● Acyclovir-Resistant HSV: Intravenous foscarnet (100 mg/kg twice daily) for 14 to 21 days.
● Pain Control: may involve a combination of opiates, gabapentin, tricyclic antidepressants, &
topical capsaicin.

Prevention:
● Varicella Vaccine: For adults with HIV who do not have documented immunity to varicella-
zoster virus.
● Zoster Vaccine: For the general population without HIV.
● Postexposure Prophylaxis: varicella-zoster immune globulin (VZIG) should be administered
within 96 hours after exposure.
Guidelines for the Prevention and Treatment of Opportunistic
Infections in Adults and Adolescents with HIV
THANK YOU