What is a Type IV Immune Disorder?

Drug-Induced Type IV Immune Disorders: What You Need to Know

In these disorders, sensitized T-cells (T lymphocytes) recognize an antigen and launch an immune attack that causes inflammation and tissue damage. This process is distinct from antibody-mediated (humoral) immune reactions.

Therefore, it is crucial to understand the types of type IV reactions and their causes and symptoms for early diagnosis and proper treatment. Keep reading for a detailed insight.

What are the types of type IV reactions?

Type IV hypersensitivity is classified by the types of immune cells involved and the symptoms that appear. They are listed as follows:

1. Contact Hypersensitivity (Type IVa): When molecules such as nickel or poison ivy urushiol attach to our skin, they alter the proteins on the skin and make them antigenic. When antigens meet with Langerhans cells, the next step is to present them to CD4+ T (helper-T) cells, which causes inflammation. This inflammation is usually seen as dermatitis.
2. Tuberculin-Type Hypersensitivity (Type IVb): During a Mantoux test, sensitised T cells react to the tuberculin, which releases cytokines and gathers macrophages. As a result, the area swells and becomes hard.
3. Granulomatous Hypersensitivity (Type IVc): Long-term contact with persistent antigens can create granulomas, which are collections of cells in the immune system trying to isolate these antigens, as in tuberculosis, sarcoidosis, and leprosy.
4. T-Cell-Mediated Cytotoxicity (Type IVd): When people experience Stevens-Johnson syndrome or toxic epidermal necrolysis, the activity of CD8+ T (CD8 positive T-cells) cells kills affected tissues.

What are the Causes of Type IV Immune Disorders?

These disorders develop when the T-cell-mediated immune response is inappropriately triggered or poorly regulated, leading to an exaggerated attack on antigens that are either harmless (e.g., nickel, a drug) or persistent (e.g., mycobacteria). The most important causes are:

• Persistent Infections : Specific pathogens, such as Mycobacterium tuberculosis and Histoplasma capsulatum, can activate the immune system for a long time, creating granulomas. Although the immune system tries to prevent infection, too much action from T-cells might harm the body's tissues.
• Autoimmunity : Type 1 diabetes and multiple sclerosis are examples of autoimmune diseases in which T cells become active against antigens present within the body. In multiple sclerosis, myelin-specific T cells assault the nervous system, resulting in demyelination.
• Chemical Sensitisation : Exposure to small reactive chemicals, like poison ivy urushiol or nickel, can modify skin proteins. These altered proteins become antigenic, provoking a T-cell-driven response, often resulting in contact dermatitis.
• Chronic Antigen Exposure : Prolonged exposure to environmental antigens, such as beryllium or silica, can trigger sustained immune reactions, leading to tissue fibrosis and conditions like hypersensitivity pneumonitis.
• Drug-Induced Hypersensitivity : Some medications, like certain antibiotics or anticonvulsants, can activate cytotoxic T cells, causing severe reactions, including Stevens-Johnson syndrome or toxic epidermal necrolysis.
• Transplant Rejection : In cases of graft rejection, recipient T cells recognise donor tissue as foreign and mount an immune attack, leading to inflammation and tissue destruction.

What are the symptoms of type IV immune disorders?

Symptoms depend on the subtype of type IV immune disorders:

• Contact Dermatitis: Red, itchy rash with blisters after skin exposure.
• Tuberculin Reaction: Local swelling and redness after TB (tuberculosis) antigen exposure.
• Drug-Induced Syndromes: Severe reactions such as SJS/TEN (Stevens-Johnson syndrome/toxic epidermal necrolysis)—fever, blisters, painful skin detachment.
• Pustular Eruptions: Widespread pustules within days of exposure, seen in AGEP (acute generalised exanthematous pustulosis).

What is the diagnosis for Type IV immune disorders?

Diagnosis is based on clinical history and investigations, such as:

• Patch Testing– Identifies specific contact allergens (e.g., metals, chemicals).
• Intradermal Skin Tests– e.g., the Mantoux test for tuberculosis.
• Biopsy– Provides histology showing T-cell–driven inflammation.
• Drug Reaction Assessment– Review medications and symptoms to identify offending agents.

What are the Treatment Approaches for Type IV Immune Disorder?

Listed below are the treatment approaches for Type IV immune disorders:

What are the complications of type IV immune disorder?

Type IV disorder complications can range from mild to severe, such as:

• Skin integrity lossin SJS/TEN increases infection risk.
• Granuloma formationis present in diseases like TB or sarcoidosis.
• Chronic inflammationleading to scarring or organ dysfunction.
• Frequent relapsesin chronic contact dermatitis occur if exposure continues.

Managing Type IV disorders, especially severe cases, requires medications, diagnostics, hospitalisation, and long-term tracking.

Type IV immune disorders are complex, cell-mediated reactions that can range from contact rashes to life-threatening drug reactions. Although symptoms may be delayed, timely diagnosis, avoidance of triggers, and appropriate therapy can prevent serious outcomes.

Patients should collaborate with healthcare providers to create tailored treatment and prevention strategies.

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