2.5.11 Skin manifestations of HIV infection

Grading & Level of Importance: C

Review:
2021

W. Burgdorf, Munich; A. Salam, J. McGrath, London
Revised by A. Salava, E. Hiltunen-Back, A. Ranki, Helsinki

Definition

Human immune deficiency virus (HIV) – infected patients have significantly more skin problems than the general population. Some of the skin manifestations may have an indicator character and should awake the need for prompt HIV-testing.

Aetiology & Pathogenesis

HIV infection is transmitted by sex, contaminated needles or blood products, and across the placenta from infected mothers to the infants. HIV causes a lifelong infection, slowly destroying the body’s immune defenses and ending in the acquired immune deficiency syndrome (AIDS). Along the decrease of CD4 cells and immune response deterioration, numerous skin and mucous membrane symptoms develop, such as infections, dermatoses, malignancies and drug eruptions.

Signs & Symptoms

Primary infection of the HIV virus can cause acute flu-like symptoms with a generalized transient maculopapular exanthematous skin eruption affecting face, throat, trunk and proximal limbs. The other symptoms include fever, fatigue, sore throat with occasional apthae and sometimes also diarrhea but no respiratory infection symptoms. The primary infection can also be asymptomatic; usually the acute infection ends with clinical recovery in 2-4 weeks. Chronic HIV infection is a period of clinical latency. This stage can last for years or even decades. During this time, a multitude of skin problems (e.g. infections, dermatoses, skin cancer/Kaposi sarcoma) often develop. There is not any specific  skin symptom. Skin manifestations have a tendency to recur and may show an atypical or more severe course;
Symptoms in secondary HIV may be viral, bacterial and parasitic infections and may have a clinical different pattern to the usual course (herpes zoster, molluscum contagiosum, HPV condyloma, hairy leukoplakia, chronic pruritus, seborrhoeic dermatitis).

 

Most important is to consider a possible HIV-infection in patients with skin problems that follow uncommon or severe disease courses, or are recurrent and refractory to standard therapy.

Localisation

Anywhere on the skin, localised or disseminated, oral cavity, ano-genital region.

Classification

Acute and chronic phase of HIV infections (see above “Symptoms”).

Laboratory & other workups

Diagnosis of the HIV-infection with HIV antigen/antibody test and confirmation with Western blot. The HIV AgAb test becomes positive earliest at 2 weeks and latest at 3 months after infection.  A positive screening test always requires a second confirmatory test. In new-borns detection of the HIV-virus with nucleic acid quantitation (viral copies/ml). Pregnant women should be routinely offered HIV testing and counseling, since infection of the fetus can be prevented with ART during pregnancy.

Dermatopathology

Depends on the stage of the disease and the type of associated disease. Lymphomas or CVA.

Course

Unlike the sporadic forms of the listed skin problems, in HIV-infected patients they may be refractory to standard therapy and may follow an untypical and more severe course. HIV-associated psoriasis and Kaposi’s sarcoma usually respond rapidly to antiretroviral therapy.

 

Course of the HIV-infection:
Acute retroviral syndrome (Primary HIV infection)/ WHO stage 1.
During the acute symptoms, HIV viral load (viremia) is very high in the body and the infected person is highly infectious. HIV-antibody test usually turns positive 2-4 weeks after the onset of symptoms while a combined antibody- antigen test (HIVAgAb) becomes positive already 2-4 weeks after the transmission of HIV infection; in rare cases it may take up to 3 months for the antibodies to turn positive. In newborns, HIV-infection can be confirmed by PCR based quantitation of HIV RNA.

 

Chronic HIV-infection (Clinical latency) )/ WHO stages 2-3
 the severity of the skin problems often progresses corresponding to the immunosuppression. The total amount CD4-positive T-lymphocytes in the blood is used as a marker of the severity of the immunosuppression (normally over 0,4 E9/l).

 

AIDS stage (WHO stage 4)
In this advanced stage, the CD4 cell count has dropped below 0,200 x 109/l,  HIV viral load is high and the person is highly infectious. Typically Kaposi’s sarcoma, caused by HHV-8, occurs in this stage.

 

AIDS-defining skin conditions include Kaposi’s sarcoma, caused by HHV-8. 

Complications

Complications of an early infectious stage: none. In the latency stage depends on the type of infectious agents or dermatoses, causative agents may become resistant to standard therapy regimens. Severe drug reactions due to HIV drugs may occur.

Diagnosis

Primary infection of HIV exanthema. Latency stage with different associated skin diseases (see above).


HIV-specific skin manifestations are usually suspected based on clinical features; laboratory, microbiological (skin infections) and histopathological tests (dermatoses, malignancies) are necessary for confirmation. The viral load (virus copies/ml) and degree of immunosuppression (CD4-cell count) should be determined; screening tests for other STIs should be carried out.

Differential diagnosis

In particular the early HIV exanthema is difficult to differentiate. The amount of differential diagnoses in the latency stage of HIV infection depends on the type of skin symptom.

Prevention & Therapy

Avoidance of skin associated symptoms is depending on prevention programs of HIV infection.


Early initiation of antiretroviral therapy (ART) enables people living with HIV to stay alive and reduces the risk of transmitting the virus to partners. WHO guidelines recommend ART is to be started for all patients diagnosed with HIV, irrespective of their CD4 cell count. Today, about 30 different anti-retroviral drugs are available. The treatment is lifelong. Management of antiretroviral medication is usually carried out by an HIV-specialist.


Skin infections might require more effective (e.g. intravenous) and longer antibiotic, antiviral and antifungal therapies;  (e.g. infections due to Candida albicans, herpes simplex). Similarly, dermatoses in HIV-infected patients often require a longer and more efficient therapy to achieve remission. 

Special

It is important that the patients  with unclear skin lesions are referred to dermatologists and specialist centers.

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