Immunodeficiency

What is immunodeficiency?

Immunodeficiency can be caused by inherited syndromes, infections, drugs, medical conditions, pregnancy, ageing and many other factors. Immunodeficiency is defined as inadequate functioning of the immune system. The severity varies leading to different types of infection. It can occur at multiple points across the immune response. It can then lead to:

• Serious bacterial infections (e.g. Staphylococcus aureus)
• Severe fungal infection (e.g. oral candidiasis)
• Persistent viral infections (e.g. extensive molluscum contagiosum)
• Failure to thrive in infants and children
• Infections due to unusual or opportunistic organisms
• Delayed recovery from illness
• Non-infectious granulomatous skin disorders
• Certain cancers such as Epstein Barr virus-associated B-cell lymphoma, polyomavirus-associated Merkel cell carcinoma and Human herpesvirus-8-associated Kaposi sarcoma.

Immunodeficient people that become unwell should be carefully evaluated and infection should be treated aggressively.

Primary immunodeficiency diseases

Primary immunodeficiency diseases are present from birth and persist lifelong. They are due to uncommon or rare genetic defects and there is often a family history of the condition. The World Health Organization lists 185 different primary immunodeficiency diseases. They include:

• Common variable immune deficiency
• X-Linked agammaglobulinaemia
• Selective IgA deficiency
• Severe combined immune deficiency
• Chronic granulomatous disease
• Wiskott-Aldrich syndrome
• Hyper-IgM syndrome
• DiGeorge syndrome
• IgG subclass deficiency and specific antibody deficiency
• Ataxia telangiectasia
• Hyper-IgE syndrome
• Complement deficiencies
• Interleukin 7 deficiency (predisposes to viral warts)

Acquired immunodeficiency

The best known secondary or acquired immunodeficiency disease is due to infection with human immunodeficiency virus (HIV) which leads to AIDS (acquired immunodeficiency syndrome).

Human T-cell lymphotropic virus type 1 (HTLV-1) also leads to immune deficiency.

Cancers, particularly blood disorders that affect white blood cells such as leukaemia and lymphoma, may lead to severe immune deficiency.

Immunosuppression due to drugs

Immunosuppression is general dampening of the immune response, usually in response to immunosuppressive drugs. The immune response is still mounted but it is not as efficient or efficacious.

Immunosuppressive drugs include:

• Systemic corticosteroids (for children, prednisone >2mg/kg/day for 2 weeks or >1mg/kg/day for >4weeks), which suppress T lymphocytes via TH1, TH2 and TH17 pathways
• High-dose methotrexate
• Ciclosporin
• Azathioprine
• Mycophenolate
• Cyclophosphamide
• Biologic agents

Lower doses or shorter courses of systemic steroids are not considered significantly immunosuppressive. Low-dose methotrexate used for skin diseases mainly acts as an anti-inflammatory drug and is only weakly immunosuppressive.

How do skin infections relate to immunodeficiency?

Skin infections become more common as the number of CD4+ T-lymphocytes reduce.

Mild reduction in CD4+ T-lymphocyte count (>200) is part of normal ageing. This leads to an increased incidence of herpes zoster (shingles) and in countries where it is prevalent, old-world or classic Kaposi sarcoma.

Moderate reduction in CD4+ T-lymphocyte count (200-50) occurs in some elderly patients, newborn babies, and in primary immunodeficiency diseases. The deficient T lymphocytes tend to produce the TH2 class of cytokines, which lead to enhanced allergic reactions characterised by eosinophilic infiltrations. These include:

• Atopic eczema with staphylococcal infection
• Enhanced and persistent insect bite reactions – often with blisters
• Eosinophilic folliculitis
• Transient acantholytic dermatosis (Grover disease)
• Prurigo (red itchy bumps)
• Eosinophilic cellulitis
• Hypereosinophilic syndrome
• Eosinophilic disorder of myeloproliferative disease

Infections may include extensive viral warts and crusted scabies.

Severe reduction in CD4+ T-lymphocyte count (<50) usually indicates infection with HIV. It leads to unusual manifestations of infection, and infection with organisms that are normally harmless in healthy individuals. It seems that the immune system tolerates the presence of organisms that it normally fights to eradicate from the skin. Examples include:

• Verrucous or ecthymatous forms of herpes zoster (CD4 <25),
• Bacillary angiomatosis
• Cryptococcosis
• HIV-associated Kaposi sarcoma
• Hairy leukoplakia

What tests should be done for immunodeficiency or immune suppression?

Because the appearance of skin conditions is often different in immune suppressed individuals compared to normal, unusual conditions and infections must be considered. Tests include repeated:

• Swabs for viral and bacterial culture
• Scrapings for mycology
• Biopsies for histopathology and microbiological cultures.