Abstract
To the Editor:
Case Report
A., a 10-year-old boy, presented with a history of sudden onset episodes of difficulty in walking, and climbing up on cupboards for three weeks, and was admitted for further evaluation and management. Detailed neurological evaluation did not reveal any abnormality. As he had functional motor symptoms, he was diagnosed having dissociative motor disorder, which is a form of conversion disorder. Psychosocial stressors were assessed and were primarily managed using nonpharmacological strategies. For disturbed sleep and anxiety, clonazepam 0.5 mg was administered at bedtime. He was not on any other medication including over-the-counter drugs at that time. On the sixth day after starting clonazepam, he developed skin peeling on the finger tips and a burning sensation on his palms that worsened while immersing hands in cold water. Dermatologist opinion was sought, and on examination the findings included mild scaling of the finger tips and hyperlinear lesions over the palmar aspect of fingers. On immersion of hands in water, there was exaggerated wrenched skin along with burning pain over the areas leading to withdrawal of the hands. He was previously exposed to clonazepam intermittently three weeks before for a maximum duration of two days without any dermatological problems. There was no major medical illness in the past and there was no history of allergy or drug reaction. His elder sister, who had dissociative disorder, had developed skin rashes following medications but further details were not available. Investigations including complete blood count, and liver and renal function tests were normal. Naranjo adverse drug reaction (ADR) probability scale score (Naranjo et al. 1981) suggested a probable association. Considering a possibility of clonazepam-induced localized exfoliating rash with paresthesia (“burning skin syndrome”), medication was discontinued on the same day. He was prescribed fluticasone propionate cream and elovera cream containing 10% aloe extract along with vitamin E IP 0.5% with which the lesions subsided after one week without any recurrence thereafter.
Discussion
A. developed acral dermatitis (localized exfoliating rash with paresthesia) following clonazepam treatment for sleep and anxiety, which resolved after discontinuation of the medication and symptomatic treatment. Kawasaki disease, a pediatric autoimmune acute febrile mucocutaneous lymph node syndrome, may present with desquamation of fingers and toes (Michie et al. 2000), though in our case other systemic manifestations were absent. Other autoimmune disorders such as lupus erythematosus may also present with acral manifestations (McCauliffe 2001) and are usually associated with other typical signs of the disorder. Psoriasis affecting palms may present with scaling though typically lesions red, raised and well demarcated. Keratolysis exfoliativa (or recurrent focal palmar peeling), also presents with peeling of palms, less commonly soles, in young adults, usually in summer and related to sweating (Lee et al. 1996). The use of degreasing chemicals can produce similar acral peeling, though such exposure was absent in our case. Epidermolysis bullosa simplex, specifically the Weber-Cockayne variant, may present with blistering of palms and soles, following friction (Horn and Tidman 2000). Rarely, familial acral peeling skin syndromes with autosomal recessive mode of transmission have been reported which present with episodic desquamation of hands and feet (Wakade et al. 2009).
We did a PUBMED search using key words, “clonazepam,” “acral dermatitis,” “acral peeling,” “burning skin syndrome,” and “localized exfoliating rash with paresthesia” but could not find any report of such adverse reaction with clonazepam. Nevertheless, one case of burning mouth syndrome has been reported to occur with clonazepam treatment, which resolved following discontinuation of medication and reappeared on starting the medication (Culhane and Hodle 2001). As no other cause was evident, and the adverse reaction had clear temporal relationship with clonazepam treatment, it is likely to be drug-induced. Although the patient was exposed previously to clonazepam, the duration was shorter than the current exposure, which might explain the absence of such reaction earlier.
Clonazepam acts primarily through modulation of GABA function in the brain, via the benzodiazepine receptor, which in turn leads to chloride influx and enhanced GABAergic inhibition of neuronal firing (Jenner et al. 1986). Also, clonazepam has been reported to decrease the serotonin utilization by neurons (Jenner et al. 1986). Interestingly, serotonergic mechanisms are associated with burning mouth syndrome and serotonin reuptake inhibitors have been found to be helpful in such cases (Klasser et al. 2008). The modulation of serotonergic nociceptive neurons by clonazepam could be the possible mechanism underlying the localized exfoliating rash with paresthesia (burning skin syndrome) in our case.
Our case responded to medication discontinuation and symptomatic treatment with a combination of fluticasone propionate, elovera extract, and vitamin E cream. Fluticasone propionate is a carbothioate corticosteroid, which has potent anti-inflammatory effect and reported to be effective for acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis, and vitiligo (Roeder et al. 2005). It has been found to be safe and effective even in pediatric patients with atopic dermatitis (Kirkup et al. 2003). Topical Vitamin E has potent efficacy against early inflammatory and oxidative stress responses in mice (Rahman et al. 2008), and has been used in children for reducing scars, probably through its antioxidant effect (Khoosal and Goldman 2006). Aloe vera extract has been helpful for dermatitis and other conditions through its potential anti-inflammatory effect (Feily and Namazi 2009).
As seen in our case study, localized exfoliating rash with paresthesia was probably associated with exposure to clonazepam that resolved after discontinuation of medication. Although uncommon, such adverse reactions need to be identified early and also be differentiated from other causes of acral peeling that presents in childhood in order to improve compliance with the medication.
Disclosures
Drs. Munoli, Preharaj, and Bhatt have no conflicts of interest or financial ties to disclose.