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Dermatological Toxicities of ART. HAIVN Harvard Medical School AIDS Initiative in Vietnam. Learning Objectives. By the end of this session, participants should be able to: Explain how to grade dermatological toxicity
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Dermatological Toxicities of ART HAIVN Harvard Medical School AIDS Initiative in Vietnam
Learning Objectives By the end of this session, participants should be able to: • Explain how to grade dermatological toxicity • Describe the clinical manifestation of rash and explain how to manage rash caused by: • NNRTI • Cotrimoxazole • Abacavir • Explain the management of a patient with Stevens-Johnson Syndrome
Evaluating the Rash (1) –How to Find the Etiology? • Take a thorough history of the rash and concomitant symptoms: • ask about other possible allergens • find out where and when exactly the rash started on the body • Get a good medication history • Do a thorough medical and laboratory evaluation to exclude other etiologies
Evaluating the Rash (2) – Is Rash Caused by ARV? • Did the patient recently start an ARV likely to cause rash? • Does the patient has a known history of allergies to other medications that he/she is taking? • Is the treatment of other causes of rash not helpful? • Are evaluations of other causes of rash negative?
Which Medications are Likely to Cause Rash? Least likely Somewhat likely Most likely • Fluconazole • 3TC • D4T • TDF • LPV/r • Pyrazinamide • Ethambutol • CTX • NVP • EFV • ABC • Rifampicin • Isoniazid
Medications Likely to Cause Rash t 2007; **AIDS 2007, 21:2293–2301, Lancet 2004; 363: 1253–63
NNRTI Rash • Rash is common with both NVP (37%) and EFV (26%) • Most rashes are mild, requiring treatment with antihistamines without stopping the NNRTI • NVP is more likely to cause severe (grade 3-4) rash
Management of NNRTI Rash: Stage 1- 2 • Continue ARV; Give antihistamines • Delay escalating dose of NVP • Closely monitor for development of systemic symptoms, worsening rash, LFT elevations: • Stop CTX if this was started around same time as ARV and allergy can’t be ruled out • Stop or change ARV if rash progresses to stage 3 or 4
Management of NNRTI Rash: Stage 3 (1) • If NNRTI (e.g. NVP) is the most likely cause, stop it and continue the 2 NRTI drugs for up to 7 days • Stop CTX if this was started around the same time as ARV, and allergy to it is also possible • Give antihistamines
Management of NNRTI Rash: Stage 3 (2) Follow-up in 3-7 days:
Management of NNRTI Rash: Stage 4 • Stop all medications • Close monitoring and care • Restart ARV and CTX when rash, fever and other symptoms have resolved: • NNRTI should be changed to another NNRTI or PI or TDF • Start CTX 2 weeks after starting ARV and patient stable
Cotrimoxazole Allergy • Clinically: • Maculopapular rash • Can have fever • Usually within first few weeks of treatment • Epidemiology • No studies in Asia • In Africa, about 2% had allergy to CTX* • Resolves when drug is stopped Lancet. 2004 Oct 16-22;364(9443):1428-34.
Management of CTX Rash Vietnam MOH guidelines on treatment of HIV/AIDS, 2009
Cotrimoxazole Desensitization (1) WHO August 2006: Guidelines on co-trimoxazole prophylaxis
Cotrimoxazole Desensitization (2) • Offer antihistamines • Review daily or give specific instructions on how to respond to any reaction:
Abacavir Hypersensitivity (1) • Incidence: 3 - 6% • Time of presentation: • Median = 11th day • 93% of cases occur in the first 6 weeks
Abacavir Hypersensitivity (2) • Clinical symptoms: • Most common: fever, maculopapular rash, fatigue • GI Symptoms: nausea, vomiting, diarrhea, abdominal pain • Respiratory symptoms: cough, shortness of breath
AbacavirHypersensitivity (4): Treatment • Stop ABC immediately if hypersensitivity is suspected: • Symptoms will usually improve within a few days • Note ABC hypersensitivity in the patient record • Never give ABC again • Notify the patient of the reaction and counsel them not to take ABC again • For severe reactions or hypotension: • Admit to hospital or ICU
What is Stevens Johnson Syndrome? • Severe reaction, most commonly triggered by medications • Characterized by: • fever and mucocutaneous lesions • necrosis and sloughing of the epidermis • HIV positive patients are at higher risk for SJS than HIV negative • Mortality rate usually less than 5%
SJS: Skin Lesions (1) • Begins 1-3 weeks after drug initiation • Typically fever and flu-like symptoms occur 1-3 days before rash onset • Initial skin lesions: • Poorly defined macules with purpuric centers that coalesce to form blisters • Symmetrically distributed • Located on face and upper trunk • Lesions may burn or be painful
SJS: Skin Lesions (2) • Lesions then progress to epidermal detachment • Rash is most severe on 4th day • Nikolsky's sign shows extensive epidermal detachment: • separation of the outer layer of the epidermis from the basal layer when lateral pressure is applied to the skin
Stevens Johnson Syndrome Fein, J. D. et al. N Engl J Med 2005;352:1696
Stevens Johnson Syndrome: Other Findings • Mucosal involvement • conjunctiva, oral cavity, genital mucosa • esophagus occasionally involved • Ophthalmologic involvement: • conjunctival lesions • Pulmonary involvement: • dyspnea, cough with sputum, hypoxemia • interstitial infiltrates, pulmonary edema, bronchiolitis obliterans
Stevens Johnson Syndrome: Management • Early recognition and immediate withdraw of any potential causative agent • ICU transfer (burn unit) • Topical antibacterial ointments or silver sulfadiazine • Surgical debridement to remove necrotic epidermis • Ophthalmologic care
Key Points • Common drugs that cause rash in PLHIV include NNRTIs, CTX, and Abacavir • Skin rashes are graded by severity using grades 1 - 4 • Grade 1-2 may resolve with antihistamines and continuation of the drug • Grades 3 and 4 usually necessitate medication withdrawal or change • SJS is best managed by early recognition and withdrawal of causative drug
Thank you! Questions?
