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Dermatological Toxicities of ART: Grading and Management

Learn how to grade and manage dermatological toxicities caused by ART medications, including NNRTI, Cotrimoxazole, and Abacavir. Explore the differential diagnosis of rashes in PLHIV and understand the management of Stevens-Johnson Syndrome.

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Dermatological Toxicities of ART: Grading and Management

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  1. Dermatological Toxicities of ART HAIVN Harvard Medical School AIDS Initiative in Vietnam

  2. 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

  3. Differential Diagnosis of Rash in PLHIV

  4. Grading Rash

  5. Four Grades of Rash (1)

  6. Four Grades of Rash (2)

  7. Four Grades of Rash (3)

  8. Evaluating the Possible Causes of Rash

  9. 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

  10. 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?

  11. 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

  12. Medications Likely to Cause Rash t 2007; **AIDS 2007, 21:2293–2301, Lancet 2004; 363: 1253–63

  13. NNRTI Rash

  14. 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

  15. 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

  16. 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

  17. Management of NNRTI Rash: Stage 3 (2) Follow-up in 3-7 days:

  18. 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

  19. Management of NNRTI Rash:Vietnam MOH Guidelines (1)

  20. Management of NNRTI Rash:Vietnam MOH Guidelines (2)

  21. Cotrimoxazole Rash

  22. 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.

  23. Management of CTX Rash Vietnam MOH guidelines on treatment of HIV/AIDS, 2009

  24. Cotrimoxazole Desensitization (1) WHO August 2006: Guidelines on co-trimoxazole prophylaxis

  25. Cotrimoxazole Desensitization (2) • Offer antihistamines • Review daily or give specific instructions on how to respond to any reaction:

  26. Abacavir Hypersensitivity Rash

  27. Abacavir Hypersensitivity (1) • Incidence: 3 - 6% • Time of presentation: • Median = 11th day • 93% of cases occur in the first 6 weeks

  28. Abacavir Hypersensitivity (2) • Clinical symptoms: • Most common: fever, maculopapular rash, fatigue • GI Symptoms: nausea, vomiting, diarrhea, abdominal pain • Respiratory symptoms: cough, shortness of breath

  29. Abacavir Hypersensitivity (3)

  30. 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

  31. Stevens Johnson Syndrome (SJS)

  32. 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%

  33. 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

  34. 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

  35. Stevens Johnson Syndrome Fein, J. D. et al. N Engl J Med 2005;352:1696

  36. Stevens Johnson Syndrome

  37. 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

  38. 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

  39. 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

  40. Thank you! Questions?

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