Jumihaidokuto (Shi-Wei-Ba-Du-Tang), a Kampo Formula, Decreases the Disease Activity of Palmoplantar Pustulosis

Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by sterile intraepidermal pustules associated with erythematous scaling on the palms and soles. Jumihaidokuto is a traditional herbal medicine composed of ten medical plants and has been given to patients with suppurative skin disease in Japan. This study investigated the effect of jumihaidokuto on the disease activity in PPP patients (n = 10). PPP patients were given jumihaidokuto (EKT-6; 6.0 g per day) for 4 to 8 weeks in addition to their prescribed medications. The results showed that the palmoplantar pustular psoriasis area and severity index (PPPASI) was decreased after the administration of jumihaidokuto (p < 0.05). Therefore, Jumihaidokuto is seemingly effective against PPP.


Subjects.
The study included ten PPP patients (4 males and 6 females; age, 59-77 years; mean age, 66.0 years). A diagnosis of PPP was performed according to the clinical findings by experienced dermatologists. The patients had no other concomitant diseases.

Study Design.
The study was performed as a prospective self-controlled trial. These PPP patients were given JHT (EKT-6; 6.0 g per day; Kracie Holdings, Ltd., Tokyo, Japan) before meals, two times a day, for 4 to 8 weeks in addition to their prescribed medications, such as topical corticosteroids and oral antihistamines ( Table 1). The patients were not allowed to take any other medication during the study period. Clinical assessments were performed at week 0 and week   In addition, the percent change of the PPPASI score for each patient before and after JHT treatment was also assessed.

Statistical Analysis.
Data are presented as the mean values plus the standard error of the mean ± S.D. All statistical analyses were performed using paired -test. A value of less than 0.05 was considered to be statistically significant.

Results
Ten PPP patients were given JHT for 4 to 8 weeks. Seven out of 10 PPP patients showed an improvement in their clinical findings (Table 1). In most of these patients, the number of pustules on the palms and soles markedly decreases (Figure 1(a)). In addition, some patients showed a disappearance of hyperkeratotic lesions (Figure 1(b)). The average PPPASI of all patients was 8.34 ± 9.00 before JHT treatment. Four or 8 weeks after the administration of JHT, the average PPPASI significantly decreased (5.46 ± 7.02, < 0.01; Figure 2). No adverse event was observed during the study period.

Discussion
Traditional herbal medicine, also known as Kampo medicine in Japan, has a long history and plays a role in the prevention and treatment of various inflammatory skin diseases. Kampo medicines have been occasionally used as a treatment for PPP and certain Kampo herbal drugs are known to be effective for PPP, even when the symptom is resistant to standard treatment. For instance, orengedokuto (Huang-Lian-Jie-Du-Tang) is effective for erythematous lesions of PPP [2]. Unseiin (Wen-Qing-Yin) and keishibukuryogan (Gui-Zhi-Fu-Ling-Wan) can improve hyperkeratotic lesions of PPP [2]. Furthermore, we recently reported that the administration of JHT markedly decreased the number of pustules on the palms and soles of a PPP patient [8]. The present study demonstrated that JHT can significantly decrease the disease activity of PPP according to the PPPASI. Although there has been no reported case regarding Kampo treatment for PPP in the English literature, we found 2 clinical studies in the Japanese literature which described the effect of Kampo medicines for PPP patients. One study described that the treatment of JHT was effective for 64.9% of PPP patients [9]. Another study reported that the administration of JHT for 12 weeks resulted in a mild improvement in 49.9% of PPP patients [10]. These reports are considered to be compatible with the result of the present study. In contrast, in the present study, three patients showed no improvement in their PPPASI score. This may be because the PPPASI scores before JHT treatment in these 3 patients were very low compared to those in the other patients. In addition, JHT is known to have side effects, including pseudoaldosteronism and myopathy, although no adverse events were observed in all patients during the present study. JHT is composed of ten medicinal plants. Among them, Bupleuri Radix and Glycyrrhizae Radix have antisuppurative and anti-inflammatory activities. Furthermore, Platycodi Radix is known to drain pus [11]. The JHT formula used in this study includes Pruni Cortex, but not Quercus Cortex. Quercus Cortex is considered to be effective for the "Okestu" symptom, which appears to correspond to blood stasis [12]. In contrast, Pruni Cortex has antisuppuration and anti-inflammatory activities and a drainage effect of pus similar to Bupleuri Radix and Glycyrrhizae Radix. In addition a recent study demonstrated that an extract of Pruni Cortex possessed an estrogenlike effect. Estrogen can act as an antagonist of androgen; therefore, Pruni Cortex may reduce sebum secretion via the similar function of estrogen. This hypothesis may explain the