Title: Zinc Deficiency Presenting with Necrolytic Acral Erythema and Coma
Abstract: Necrolytic acral erythema is a rare cutaneous diagnosis that was first described in 1996 in a cohort of Egyptian patients with hepatitis C virus infection.1el Darouti M. Abu el Ela M. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C.Int J Dermatol. 1996; 35: 252-256Crossref PubMed Scopus (90) Google Scholar Necrolytic acral erythema is more common in women, and the mean age of onset is 40 years.2Tabibian J.H. Gerstenblith M.R. Tedford R.J. Junkins-Hopkins J.M. Abuav R. Necrolytic acral erythema as a cutaneous marker of hepatitis C: report of two cases and review.Dig Dis Sci. 2010; 55: 2735-2743Crossref PubMed Scopus (23) Google Scholar The rash may present with pain, burning, or pruritus, and begins as an erythematous or violaceous patch or plaque, with or without scale.2Tabibian J.H. Gerstenblith M.R. Tedford R.J. Junkins-Hopkins J.M. Abuav R. Necrolytic acral erythema as a cutaneous marker of hepatitis C: report of two cases and review.Dig Dis Sci. 2010; 55: 2735-2743Crossref PubMed Scopus (23) Google Scholar Acutely, vesicles or flaccid bullae may be present.2Tabibian J.H. Gerstenblith M.R. Tedford R.J. Junkins-Hopkins J.M. Abuav R. Necrolytic acral erythema as a cutaneous marker of hepatitis C: report of two cases and review.Dig Dis Sci. 2010; 55: 2735-2743Crossref PubMed Scopus (23) Google Scholar We present a unique case of necrolytic acral erythema associated with zinc deficiency in a patient who did not have hepatitis C virus infection. A 34-year-old woman with a history of morbid obesity, nonalcoholic fatty liver disease, and prior Roux-en-Y gastric bypass surgery was admitted with a painful rash involving the dorsal surfaces of her hands and feet (Figure A). She reported fatigue, anorexia, nausea, periodic vomiting for 12 years that had increased to daily in the preceding 4 months, a 100-lb weight loss, alopecia, amenorrhea, cheilitis, and auditory hallucinations. She was admitted to the hospital twice in the preceding 6 months with confusion, which was attributed to her psychiatric medications and hepatic encephalopathy. Within hours of admission, her level of consciousness deteriorated, requiring intubation and transfer to the intensive care unit. The skin biopsy of her foot dorsum (Figure B) was compatible with necrolytic acral erythema. Given the association of necrolytic acral erythema with hepatitis C infection, glucagonoma, and metabolic deficiencies, hepatitis serology and nutrient levels were ordered, and an abdominal computed tomography scan performed. Aggressive enteral and parenteral nutritional supplementation was also initiated. Within 4 days, her eyes opened spontaneously and she obeyed commands. Ultimately she made a full neurologic recovery. The rash resolved with atrophic areas and postinflammatory hyperpigmentation. Although abdominal imaging showed no evidence of glucagonoma and serology was negative for hepatitis C, her serum zinc level was markedly reduced at 2 μmol/L (normal, 9.8-20.2 μmol/L). Zinc deficiency has been associated with necrolytic acral erythema in patients with and without associated hepatitis C infection. Zinc is a trace element with a number of important physiologic roles, including skin function and development. Further support for the role of zinc deficiency in necrolytic acral erythema development comes from case reports in which zinc supplementation was effective therapy.1el Darouti M. Abu el Ela M. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C.Int J Dermatol. 1996; 35: 252-256Crossref PubMed Scopus (90) Google Scholar, 2Tabibian J.H. Gerstenblith M.R. Tedford R.J. Junkins-Hopkins J.M. Abuav R. Necrolytic acral erythema as a cutaneous marker of hepatitis C: report of two cases and review.Dig Dis Sci. 2010; 55: 2735-2743Crossref PubMed Scopus (23) Google Scholar Risk factors for zinc deficiency include reduced dietary intake and increased alimentary losses in malabsorptive states. Impaired zinc absorption after bariatric surgery is an underappreciated risk factor for the development of zinc deficiency.3Salle A. Demarsy D. Poirier A.L. et al.Zinc deficiency: a frequent and underestimated complication after bariatric surgery.Obes Surg. 2010; 20: 1660-1670Crossref PubMed Scopus (91) Google Scholar Patients typically undergo routine monitoring or supplementation postoperatively to mitigate the risk of deficiency.4Gletsu-Miller N. Wright B.N. Mineral malnutrition following bariatric surgery.Adv Nutr. 2013; 4: 506-517Crossref PubMed Scopus (111) Google Scholar Clinical manifestations of zinc deficiency include erosive eczema, alopecia, cheilitis, anorexia, abdominal pain, hypogonadism, and depression.5Corbo M.D. Lam J. Zinc deficiency and its management in the pediatric population: a literature review and proposed etiologic classification.J Am Acad Dermatol. 2013; 69: 616-624.e1Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Altered mental status can occur in the setting of severe deficiency and may be explained partially by hyperammonemia resulting from impairment of the urea cycle when zinc levels are depressed.6Riggio O. Merli M. Capocaccia L. et al.Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis.Hepatology. 1992; 16: 785-789Crossref PubMed Scopus (100) Google Scholar Zinc deficiency is an underappreciated cause of necrolytic acral erythema. Of note, bariatric surgery is a major risk factor for nutrient loss (and specifically zinc deficiency), and long-term nutritional supplementation is recommended postoperatively to augment normal dietary intake. Finally, this case highlights the importance of cutaneous findings of internal disease and the role that skin biopsy can play in revealing a vital diagnosis that otherwise may have been missed.