Drug eruption due to sodium picosulfate

ARTICLE

ejd.2012.1679

Auteur(s) : Asuka Ishikawa, Kazumitsu Sugiura kazusugi@med.nagoya-u.ac.jp, Akihiro Sato, Yoshinao Muro, Masashi Akiyama

Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho Showa-ku, Nagoya 466-8550, Japan

A 62-year-old man who had been suffering from severe constipation presented with a 2-day history of pruritic papules and vesicules on the trunk and extremities. He had been prescribed sodium picosulfate, sennoside, pantethine and magnesium oxide sporadically over the course of 10 years. Medical examination revealed tense vesicles and blisters on the extremities and palms (figures 1A-B). Vital signs were within normal ranges. There were no symptoms of fever, lymphadenopathy, mucous or systemic involvement throughout the disease course. The laboratory result was negative for herpes simplex virus antibodies, varicella zoster virus IgG was 3.6 (normal range <2.0), and Epstein-Barr virus antibodies indicated previous infection.

A skin biopsy from a tense blister on the left arm revealed a subepidermal blister with eosinophilic infiltration (figures 1C-D). Direct immunofluorescence labeling of the lesional skin sections showed no IgG, IgM, IgA or C3 deposition at the basement membrane zone. Circulating anti-BP180 autoantibody was negative by ELISA. Anti-nuclear antibody was negative. Patch tests were negative for all the medicines prescribed (see above). A lymphocyte stimulation test (LST) was positive for sodium picosulfate twice; the stimulation index was 208% (normal <180%) at Day 5 and 187% at Day 33, however this LST was negative with three healthy controls. In contrast, sennoside, pantethine and magnesium oxide were all negative at Days 5 and 33. After discontinuation of all laxatives including sodium picosulfate, the patient's eruptions subsided remarkably without therapy. Thus, the case was diagnosed as sodium picosulfate-induced bullous eruption. The patient has recently taken all the laxatives except for sodium picosulfate, but he has not suffered from a drug eruption.

Sodium picosulfate is a popular laxative. It is not digested in the stomach or the small intestine; it is hydrolysated in the large intestine and transformed to active diphenole compounds. These active compounds stimulate intestinal motility and prevent water absorption, resulting in relief from constipation. Most sodium picosulfate compounds are excreted in the feces. When the usual dosage is taken, only a tiny portion is absorbed, and this is glucuronidated in the liver and excreted in urine and bile. Thus, in general, the side effects of sodium picosulfate are limited to abdominal pain and nausea.

To our knowledge, there has only been one other report of sodium picosulfate-induced drug eruptions: a fixed drug eruption reported in the Japanese literature [1]. The eruptions in that case appeared after 5 months of sodium picosulfate intake. Our patient had a ten-year history of sodium picosulfate intake. These cases suggest that long-term intake of sodium picosulfate can induce eruptions.

The pathomechanism of such eruptions is uncertain. Sennoside, another laxative, is also scarcely absorbed in the intestine, similar to sodium picosulfate, and sennoside has been reported to lead to drug eruptions after long-term intake [2-4]. We presume that drug eruptions induced by laxatives are caused by delayed T-cell hypersensitivity, which might explain why the skin eruptions occur after long-term intake. For drug eruptions to develop, it might take a long time for T cells to become sensitized or for the drug or reactive metabolites to achieve sufficient distribution. Further studies are needed to fully understand the mechanisms.

In conclusion, sodium picosulfate is generally believed to be safe, because allergic reactions are so rare. Thus, patients tend to self-medicate with it frequently and persistently for constipation. However, the present case suggests that we should be aware that sodium picosulfate can induce drug eruptions after long-term intake.

Dislosure

Financial support: This study was supported in part by a Grant-in-Aid for Scientific Research, (C) 23591617 (K.S.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by a grant from the Ministry of Health, Labor and Welfare of Japan (Y.M.) and by a Grant-in-Aid for Scientific Research, (A) 23249058 (M.A.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Conflict of interest: none.

References

1. Ohsawa J, Aihara M, Ikezawa Z, Nakajima H. A case of fixed drug eruption induced by sodium picosulfate (Laxoberon). Hifu 1990 ; 32 : 220-222(in Japanese).

2. Fujita Y, Shimizu T, Shimizu H. A case of interstitial granulomatous drug reaction due to sennoside. Br J Dermatol 2004 ; 150 : 1035-1037.

3. Sugita K, Izu K, Tokura Y. Erythema multiforme-like drug eruption caused by sennoside. Int J Dermatol 2006 ; 45 : 1123.

4. Sugita K, Nishio D, Kabashima K, Tokura Y. Acute generalized exanthematous pustulosis caused by sennoside in a patient with multiple myeloma. J Eur Acad Dermatol Venereol 2008 ; 22 : 517-519.