Dermatological Reaction to Anti-Tuberculosis Drugs

Evaluate other potential etiologies of rash and pruritus:

• Scabies and insect bites may masquerade as a drug rash. 
• Contact dermatitis (question patient about use of new lotions, soaps, perfumes, etc.). 
• Phototoxicity (may respond to sunscreens, but these may cause contact dermatitis). 
• Other drugs, especially new agents, should be evaluated as possible etiologies. 
• Other dermatologic causes; psoriasis, pityriasis, atopic dermatitis, etc.
•  Dry skin, especially in diabetic patients, may be the cause of pruritus. Consider liberal use of lotions, such as petroleum jelly and lanolin (may be purchased in a feed supply store where it is less expensive). Dry skin is a serious problem with clofazimine. Drugs should not be continued if there are systemic symptoms, fever, urticaria, mucous membrane involvement, blistering of the skin, edema of the lips or eyes, or wheezing or compromise of the airway. 
• Hypothyroidism. 
• Acneiform lesions may fl are with the use of INH, ethionamide, and clofazimine. This will usually resolve after several months, often with improvement in the patient’s acne. Standard topical antibiotic treatment may be helpful in the meantime. 
• Unusual skin lesions may be associated with HIV infection.

Dermatological Reactions
Flushing Reactions 

• Flushing and/or itching reactions of the skin without a rash usually involve the face and scalp, and occur 2 to 3 hours after medications. Redness and watering of the eyes may also occur. 
• This is usually due to rifampin (RIF) or pyrazinamide (PZA). 
• It is usually mild and resolves in time without therapy. 
• If it is bothersome to the patient, an antihistamine may be administered to treat or to prevent the reaction. 
• Patients taking INH may experience flushing and/or itching of the skin with or without a rash, plus possible hot flashes, palpitation, or headache 2 to 3 hours after consuming tyramine-containing foods (cheese, salami, red wine) or certain fish (tuna). 
• Advise patients not to ingest foods that precipitate the reaction while they are receiving INH. 

Phototoxicity 

• Warn patients about the potential for phototoxicity if they are taking PZA, clofazimine, or fluoroquinolones. 
• Caution patients to limit sun exposure and to use sunscreens. 
• Phototoxicity may occur for prolonged periods even after the causative drug is stopped. Pseudojaundice (brownish discoloration of the skin) has been reported due to rifabutin. 

Lichenoid Drug Reactions 

• Pruritic, flat-topped, violaceous papules may occur anywhere, but most commonly involve the wrists, shins, and back. 
• Mucous membranes and the scalp may also be involved. 
• Differentiation from lichen planus may be made by a biopsy showing eosinophilic infiltration. 
• Lesions may resolve while medication continues. 
• Topical hydrocortisone or antihistamines may be helpful to control pruritus. 
• Medication should not be discontinued unless an equally effective drug is available for substitution. 
• Identifying the medication responsible in a multidrug regimen may be difficult because lesions resolve slowly and EMB, INH, streptomycin, and cycloserine have all been identified as causing these lesions. 

Hives, Urticaria

• Hives and urticaria may be caused by nearly any drug in the regimen. 
• They more commonly are due to INH, RIF, PZA, ethionamide, fl uoroquinolones, and EMB

Petechial rash 

• pinpoint sized red dots under the surface of the skin caused by leakages of capillaries
• Rifampin (RIF) hypersensitivity is suspected. 
• A platelet count (CBC without differential) should be ordered. 
• If the platelet count is below normal (normal range: 150,000-450,000 platelets per microliter), stop RIF and never restart it again. Monitor the platelet count until it returns to baseline. 

Erythematous rash with fever, and/or mucous membrane involvement. 

• STOP ALL drugs immediately 
• Rule out anaphylaxis reactions (angioedema, swollen tongue and throat, flushed face, airway constriction, wheezing, difficulty breathing, hypotension). 
• Rule out Stevens-Johnson Syndrome: systemic shedding of mucous membrane and fever. It can be life threatening. Immediate urgent care is required. 

Pharmacological Interventions

• They can be given prior to the anti-tuberculosis drug or as needed. 
• Diphenhydramine (Benadryl) 
• 25 to 50 mg PO, IV, or IM given before the medication, and then every 4 to 6 hours as needed may lessen skin irritation. 
• If patients become drowsy, caution them not to drive or operate machinery. 
• Other antihistamines: Chlorpheniramine 
• 4 mg PO before the medication and then every 4 to 6 hours as needed; hydroxyzine (Atarax) 25 mg PO or IM QID (can be increased to 50 mg QID); or loratadine (Claritin) 10 mg PO before the medication. 
• Hydrocortisone cream
• can be used topically. 
• Low-dose prednisone 
• (10 to 20 mg/day) for several weeks can be tried if other measures are not helpful.

Re challenge Therapy

• If treatment of TB can not be interrupted (severely ill with tuberculosis), try three new drugs (different class of drugs). Second-line anti-TB drugs such as 4 injectable aminoglycosides (streptomycin, amikacin) and 2 oral agents can be used. 
• If rash has improved substantially, anti-TB drugs can be restarted one by one every 2-3 days. 
• First, start with RIF because of its efficacy and is the least likely to cause rash. 
• Second, INH can be added after 3 days. 
• Third, PZA or EMB can be added after 3 days of INH. 
• Monitor signs and symptoms of rash. If rash recurs at any point; the last agent added should be removed.

References:

1. http://www.currytbcenter.ucsf.edu/sites/default/files/mdr_07advreact.pdf
2. http://www.uphs.upenn.edu/TBPA/treatment/managingsideeffects.pdf
3. http://health.utah.gov/epi/diseases/TB/resources/treatment/management_common_side.pdf