Drug hypersensitivity syndrome in a patient receiving vismodegib
Authors: Thomas Lam, Stephen E. Wolverton, Carrie L. Davis
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Vismodegib (Erivedge) is a hedgehog signaling pathway inhibitor that is FDA-approved for the treatment of advanced basal cell carcinoma (BCC).1Sekulic A. Migden M.R. Oro A.E. Dirix L. Lewis K.D. Hainsworth J.D. et al.Efficacy and safety of vismodegib in advanced basal-cell carcinoma.N Engl J Med. 2012; 366: 2171-2179Crossref PubMed Scopus (1123) Google Scholar Common adverse effects include nausea, vomiting, dysgeusia, decreased appetite, and weight loss.1Sekulic A. Migden M.R. Oro A.E. Dirix L. Lewis K.D. Hainsworth J.D. et al.Efficacy and safety of vismodegib in advanced basal-cell carcinoma.N Engl J Med. 2012; 366: 2171-2179Crossref PubMed Scopus (1123) Google Scholar Here we present a patient treated with vismodegib who developed drug hypersensitivity syndrome (DHS). A 77-year-old woman presented with numerous primary and recurrent BCCs on her face, trunk, and extremities. Her past medical history was significant for psoriasis that was treated with whole body radiation decades earlier and currently controlled with ustekinumab 45 mg subcutaneously every 3 months for the past 2 years. After much consideration and numerous prior surgeries, she was started on oral vismodegib 150 mg daily to treat more than 20 primary and recurrent BCCs (off-label indication). Three weeks into treatment, nausea, vomiting, dysgeusia, decreased appetite, and weight loss abruptly developed; all are common adverse effects of vismodegib. Additionally, she had chills, myalgias, and extreme fatigue. The medication was discontinued due to intolerability. Because there were rare reports of treatment-emergent electrolyte disturbances in clinical trials of vismodegib,2Erivedge [full prescribing information]. Genentech USA, Inc, South San Francisco, CA2012Google Scholar empirical laboratory specimens drawn 2 days after discontinuing the medication were remarkable for AST 143 U/L (normal 15 to 41), ALT 200 U/L (normal 7 to 35), alkaline phosphatase 345 U/L (normal 32 to 120), and total bilirubin 4.4 mg/dL (normal 0.3 to 1.2). White blood cell count was normal at 7.5 but with eosinophilia of 17.9% (absolute eosinophils 1300/μL). Basic metabolic profile was normal. Due to the mixed pattern of liver abnormalities, abdominal ultrasound was performed and was noncontributory. Liver panel was improved 10 days after discontinuing vismodegib and was completely normal after 1 month. By this time, her only complaint was a residual "fuzzy tongue" sensation that resolved over the next 3 months. A thyroid stimulating hormone and free T4 level were normal 4 months later.3Husain Z. Reddy B.Y. Schwartz R.A. DRESS syndrome: Part II. Management and therapeutics.J Am Acad Dermatol. 2013; 68: 709.e1-709.e9Abstract Full Text Full Text PDF PubMed Scopus (227) Google Scholar Repeat laboratory evaluation after her next ustekinumab injection, including white blood cell count of 7.4 with 0.9% eosinophils, was also normal. Given the mixed hepatobiliary abnormalities with peripheral eosinophilia and systemic symptoms reported 3 weeks after starting vismodegib and complete resolution following discontinuation, we believe this patient had a DHS secondary to vismodegib.4Knowles S.R. Shear N.H. Cutaneous drug reactions with systemic features.in: Wolverton S.E. Comprehensive Dermatologic Drug Therapy. 2nd ed. Saunders Elsevier, Philadelphia, PA2007: 977-988Google Scholar It is unclear what role her concurrent use of ustekinumab played, but she has not had recurrence of her symptoms or laboratory abnormalities following continued use of this medication alone. In conclusion, DHS should be included as a potential adverse effect of vismodegib. Practitioners should be made aware of this possibility so that patients reporting severe symptoms are given appropriate laboratory and clinical evaluations for prompt diagnosis and management.5Husain Z. Reddy B.Y. Schwartz R.A. DRESS syndrome: Part I. Clinical perspectives.J Am Acad Dermatol. 2013; 68: 693.e1-693.e14Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar