Generalized eruption with histopathologic toxic epidermal necrolysis caused by occupational exposure to thiourea dioxide

ARTICLE

Auteur(s) : Yumi Aoyama, Keiko Kouchi, Yuko Hiramitsu, Hiroaki Iwata, Yasuo Kitajima

Department of Dermatology, Gifu University School of Medicine, Yanagido, 1-1, Gifu City, 501-1194, Japan

Occupational exposure to chemicals can cause severe cutaneous reactions similar to erythema multiforme (EM), Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). We report an occupational dermatitis associated with thiourea dioxide, manifesting as histopathologic epidermal necrolysis.

A 58-year-old man presented with generalized maculopapular erythema and blisters, sparsely distributed on both arms, the trunk, right thigh and face, excluding the mucous membranes. The patient had worked in the textile spinning industry for over 30 years without experiencing any skin problems. 3 weeks after first using thiourea dioxide, he developed skin erythema with erosion on the right arm and thigh. He wore goggles, a mask and cotton gloves while scooping the powdered thiourea dioxide into a water tank, several times a day. He was exposed to thiourea dioxide dust through his clothes or cotton gloves. He recalled a slight wound on his hand, and might have had direct skin contact. He was not allergic to prescribed drugs or rubber products. None of his colleagues performing the same tasks had experienced any dermatological problems. A dermatologist diagnosed idiopathic dermatitis, and he was initially given antihistamines and 20 mg oral prednisolone. Over the next month, he continued to perform the same tasks at the same workplace. However, because his skin lesions did not improve, he presented at our hospital. We observed skin erythema with flaccid blister formations and crusting (figure 1A). Chemically-induced dermatitis was suspected. The patient was advised not to return to work, and was hospitalized. During the hospital stay, the skin erythema spread gradually over a 14-day period to sites that had not been exposed to chemicals, with flaccid blisters forming in the centers of lesions on the affected skin (figure 1B). More than 30% of the total surface area was affected.

Systemic prednisolone was increased to 30 mg/day, after which the erythema and maculopapular lesions stopped spreading, and the affected skin later exfoliated. Blood tests (including eosinophil counts and liver function tests) revealed no abnormality. Histological examination of a skin biopsy specimen revealed that lymphocytes had infiltrated into the epidermis, there were vacuolar changes in the basal keratinocytes, satellite cell necrosis and/or necrotic keratinocytes in the basal and upper epidermis (figure 1C), and blister formation with epidermal necrolysis (figure 1D) (often seen in SJS and TEN). Patch and lymphocyte stimulation tests were performed two weeks after corticosteroid therapy was tapered off, and a positive reaction was obtained for thiourea dioxide (table 1), suggesting a diagnosis of generalized eruption with histopathologic toxic epidermal necrolysis caused by occupational exposure to thiourea dioxide. Epidermal necrolysis, which we suspect was induced by activated lymphocytes, was clinically associated with exposure to thiourea dioxide.
Table 1 Results of patch testing and lymphocyte stimulation testing (LST)

^**Stimulation index (SI) is % of control value. Positive > 180%.

Thiourea dioxide, also known as formamidine-sulfinic acid and aminoiminomethanesulfinic acid, readily reduces to form sulfoxylate in water. This is widely used in the leather-processing industry; paper, pulp and board industries; photographic industry; and textile industry. It has recently been widely adopted as a substitute for sodium hypochlorite and sodium hydrosulfite, because they produce waste-water polluted by organic chlorine compounds (e.g. dioxins) and are considered environmentally unsustainable. Thiourea dioxide has a chemical structure similar to thiourea, one of the materials of polyurethane resin (figure 2). There have been no reports showing any crossreactivity of these chemicals.

Our patient was histologically diagnosed with epidermal necrolysis, often observed in patients with allergies to drugs, including those with SJS and TEN. Thiourea dioxide can potentially irritate the respiratory tract (delayed pulmonary edema), eyes (chemical conjunctivitis), skin, mouth and throat, and cause nausea and vomiting. The patient’s coworkers were exposed to the same agent without any apparent skin problems. Our patient developed hypersensitivity after a short exposure period, approximately 3 weeks, and it can be inferred that irritant contact dermatitis followed a first exposure to thiourea dioxide. Prolonged contact with damaged skin induced the sensitization. Ingested or inhaled thiourea dioxide possibly induced allergic dermatitis with histopathological changes of epidermal necrolysis spreading to non-exposed sites after 3 weeks.

Taken together, our observations show that thiourea dioxide can cause not only primary irritation, but also sensitization of lymphocytes to induce dermatitis and toxic epidermal necrolysis. Systemic dermatitis associated with trichloroethylene, an organic solvent, has been reported; diagnosed as SJS [1], EM [2] and hypersensitivity syndrome [3]. Hydrogen cyanamide, a plant growth regulator, has also been reported to induce dermatitis leading to EM and SJS [4]. All these cases of chemical sensitivity, including ours, had similar histopathological features: lymphocyte infiltration into the epidermis with vacuolar changes in basal keratinocytes, and necrosis of satellite cells/keratinocytes in the upper epidermis. Possibly, the chemicals responsible act as haptens, which stimulate TH1 cells to induce hypersensitivity reactions.

To our knowledge, this is the first reported case of histologically diagnosed toxic epidermal necrolysis arising from cellular allergy caused by skin contact with thiourea dioxide. More cases will probably occur, because this chemical is widely used worldwide. People handling thiourea dioxide must be made aware of the potential toxicity of this chemical, and properly protected so that sensitization does not occur.

Acknowledgements

References

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3 Goon AT, Lee LT, Tay YK, Yosipovitch G, Ng SK, Giam YC. A case of trichloroethylene hypersensitivity syndrome. Arch Dermatol 2001; 137: 274-6.

4 Inamadar AC, Palit A. Cutaneous reactions simulating erythema multiforme and Stevens Johnson syndrome due to occupational exposure to a plant-growth regulator. Indian J Dermatol Venereol Leprol 2007; 73: 330-2.