Efavirenz-associated skin rash: case study

01 Apr 2015
01 Apr 2015

Mr M is a 32-year old, HIV-positive patient who was initiated on ART fixed dose combination (tenofovir 300 mg, emtricitabine 200 mg and efavirenz 600 mg) on 16 September 2014. His baseline CD4 count was 200 cells/mm³. One week into treatment, he developed a generalised maculopapular skin rash with no mucosal involvement or systemic symptoms. He was not on any other drugs. How should this patient be managed?

Efavirenz and rash

Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is commonly associated with skin rash, with an estimated frequency ranging from 5- 34%. Other antiretrovirals commonly associated with skin rash include nevirapine and abacavir. Efavirenz-associated skin rash usually occurs within the 1 to 3 weeks of treatment initiation.

Skin rash associated with efavirenz may vary in severity from a mild diffuse, erythematous, maculopapular rash to severe lesions with associated blistering, desquamation or ulceration. Systemic symptoms such as fever, myalgia, transaminitis and fatigue may also accompany the efavirenz skin rash. The incidence of severe efavirenz rash such as erythema multiforme, toxic epidermal necrolysis and Stevens-Johnson syndrome is 0.1%.

Management of rash

Mild to moderate skin rash

A mild rash is described as a localised macular rash, whilst a moderate rash is a more diffuse macular or maculopapular or morbilliform rash. Mild to moderate skin rashes do not present with systemic features. The management involves continuation of efavirenz and symptomatic treatment with oral antihistamines. Very close monitoring for any deterioration of the skin rash is vital. Resolution of skin rash without drug cessation is expected to occur within 2 to 3 weeks.

Severe to life-threatening skin rash

A severe skin rash is described as a diffuse rash with associated blistering or desquamation or mucosal involvement, or systemic features. Efavirenz must be discontinued immediately. The rash should be allowed to settle before drug substitution with a protease inhibitor.

Life-threatening skin reactions include Stevens-Johnson syndrome (SJS), erythema multiforme and toxic epidermal necrolysis. Their management requires immediate discontinuation of all drug therapy and patient referral to a hospital for admission and further management.

Once the reaction has subsided, ART should be recommenced, and efavirenz substituted with a protease inhibitor and not another NNRTI such as nevirapine. Efavirenz should never be re-challenged following a life threatening skin reaction.

Management of Mr M

Other drug history was excluded in our patient. We identified efavirenz as the most likely drug suspect implicated in the skin rash. The severity of the skin rash in our patient was categorized as moderate. Efavirenz was continued in the patient and symptomatic treatment consisting of oral anti-histamines was administered. The patient had improvement of the skin rash within 1 week and complete resolution within one month. 

In Summary

  1. Take a detailed drug history and exclude other drugs that may cause skin rash such as co-trimoxazole
  2. Determine skin rash severity and manage as follows:

·         Mild/moderate skin rash: Continue efavirenz and give symptomatic anti-histamine therapy with close monitoring for deterioration

·         ​Severe/life-threatening skin rash: Discontinue efavirenz immediately. Allow skin rash to settle before substituting efavirenz with a protease inhibitor. Never rechallenge with efavirenz in a severe/life threatening skin rash.

·         All life threatening reactions require immediate referral to a hospital setting.

References

  1. Intracasso, CE, Hines, JM, Kavarik, CL. Cutaneous toxicities of antiretroviral therapy for HIV. Journal of American Academy of Dermatology. 2010; 63: 563-569.
  2. Luther, J, Glesby, MJ. Dermatologic  Adverse Effects of Antiretroviral Therapy. American Journal of Clinical Dermatology. 2007; 8(4): 221-233.
  3. Division of AIDS. Division of AIDS Table For Grading The Severity of Adult and paediatric Adverse Events. 2004  [cited 2014 09 Sep]; Available from: http://rsc.tech-res.com/Document/safetyandpharmacovigilance/         Table_for_Grading_Severity_of_Adult_Pediatric_Adverse_Events.pdf