Treatment of epidermolysis bullosa pruriginosa using systemic and topical agents
Authors: Aaron R. Mangold, Christine M. Cole, David J. DiCaudo, Mark R. Pittelkow, Aleksandar Sekulic
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: A 46-year-old Hispanic woman presented to our dermatology clinic with a 6-year history of an intermittent pruritic vesicobullous eruption on her lower legs and, to a lesser extent, on her forearms (Fig 1, A). She had failed to respond to prior treatments, including topical and intralesional corticosteroids, mycophenolate mofetil, and phototherapy. There was no family history of a similar condition. Histologic findings showed subepidermal clefts with minimal inflammation. Direct immunofluorescence on perilesional skin was negative. A complete workup for immunobullous disease and porphyria was negative. Electron microscopy demonstrated separation of the sublamina densa with a reduced number of anchoring fibrils, which was clinically consistent with dystrophic epidermolysis bullosa pruriginosa (EBP). DNA extraction from peripheral blood followed by bidirectional COL7A1 gene sequencing (GeneDx, Gaithersburg, MD) revealed a novel compound heterozygotic mutation; a guanine (G) to cytosine (C) splice site mutation at the beginning of intron 51 (IVS51+1 G→C) and adenine (A) to thymine (T) resulting in a codon mutation of glutamine (Gln) to leucine (Leu) at position 1924 (p.Gln1924Leu) on exon 69. Pruritus and excoriation are critical in unmasking skin fragility in EBP. Given the pauci-inflammatory nature of EBP, we focused on the control of pruritus with the use of ketamine 0.5% and amitriptyline 2% (KA) topical gel. With regular use of KA gel, the patient described a 90% decrease in localized pruritus and blistering. Subsequently, the patient was started on sertraline for depressive symptoms. Over the 6-month period on oral sertraline and KA gel, the patient had virtually complete resolution of localized and generalized pruritus with minor relapses (Fig 1, B). Effective treatment of EBP is challenging, and long-term outcomes are rarely described in the literature. Treatments reported to date include corticosteroids, antihistamines, cryotherapy, tacrolimus, cyclosporine, and thalidomide.1Ee H.L. Liu L. Goh C.L. McGrath J.A. Clinical and molecular dilemmas in the diagnosis of familial epidermolysis bullosa pruriginosa.J Am Acad Dermatol. 2007; 56: S77-S81Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar However, control of inflammation has not demonstrated consistent efficacy. Based on the structural fragility of EBP, unmasked by severe pruritus and scratching, we advocate focusing the treatment on the control of pruritus, minimizing trauma, and managing lower extremity edema. Topical KA is thought to act pre- and post-axonally in the transmission of pain and possibly pruritus. Poterucha et al2Poterucha T.J. Murphy S.L. Sandroni P. Rho R.H. Warndahl R.A. Weiss W.T. et al.Topical amitriptyline combined with topical ketamine for the management of recalcitrant localized pruritus: a retrospective pilot study.J Am Acad Dermatol. 2013; 69: 320-321Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar showed that topical KA had a 62% response rate in a wide variety of cutaneous disorders, without inducing systemic side effects.2Poterucha T.J. Murphy S.L. Sandroni P. Rho R.H. Warndahl R.A. Weiss W.T. et al.Topical amitriptyline combined with topical ketamine for the management of recalcitrant localized pruritus: a retrospective pilot study.J Am Acad Dermatol. 2013; 69: 320-321Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 3Poterucha T.J. Murphy S.L. Davis M.D. Sandroni P. Rho R.H. Warndahl R.A. et al.Topical amitriptyline-ketamine for the treatment of brachioradial pruritus.JAMA Dermatol. 2013; 1: 148-150Crossref Scopus (26) Google Scholar Interestingly, the concomitant use of sertraline for mild depressive symptoms further improved the patient's generalized pruritus and EBP. Sertraline has been reported as a first-line treatment for cholestatic pruritus and implicates serotonergic mediators in the pruritus of EBP.4Mayo M.J. Handem I. Saldana S. Jacobe H. Getachew Y. Rush A.J. Sertraline as a first-line treatment for cholestatic pruritus.Hepatology. 2007; 45: 666-674Crossref PubMed Scopus (240) Google Scholar The exact mechanism of action is unknown but is thought to have a regulatory action on the transmission of itch signals.5Metz M. Stander S. Chronic pruritus-pathogenesis, clinical aspects, and treatment.J Eur Acad Dermatol Venereol. 2010; 24: 1249-1260Crossref PubMed Scopus (52) Google Scholar The efficacy and minimal medication risk with the combined oral and topical therapies reported here favor this approach as a primary treatment of EBP, a disease that necessitates long-term management. Additional studies are required to further validate the efficacy of systemic sertraline and topical KA for treatment of EBP and possibly other skin conditions in which pruritus plays a key pathogenic role.