Palmoplantar pustulosis is gcurableh disease !

Palmoplantar pustulosis has been now considered as an incurable skin disease characterized by pustular eruptions on the palms and soles of the feet. The patients with this disease have been obliged to grieve their misfortune and to endure the illness for a long time with the doctorfs informations that the cause of this disease is not clear and that there is no adequate treatment regime for it.

I was a patient who had been distressed by this cursed disease with severe chest pain and backache by which I could hardly remove and sleep for 10 years, until I received the medical treatment by Dr. Maebashi in the National Akita Hospital in Japan before 9 years. Thanks to Dr. Maebashi, I completely recovered from the disease and now enjoy my life without any trouble. Dr. Maebashi has made researches in palmoplantar pustulosis and cured a number of the patients with this disease by his beneficial treatment established by him. The details of my life under medical treatment were described previously.

On the basis of my experience, I wanted to inform this good news to peoples who are now suffering from this disease and so I requested to Dr. Maebashi to describe about the disease on this site.

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By Dr. Masaru Maebashi

On April last year, I gave a special lecture about palmoplantar pustulosis and sternocostoclavicuar hyperostosis on the 18th Annual Congress of the Japanese Society of Clinical Dermatology. Although the lecture was given in Japanese for one and a half hours, here I summarize the outline of these diseases and their medical treatment in English with the hope that you can have a better understanding on these diseases.

Palmoplantar pustulosis has been regarded as an incurable disease characterized by pustular eruptions on the palms and soles of the feet, and extrapalmoplantarily on the backs of the hands and insteps of the feet. In the United States, pulmaplanta pustulosis are included in the category of psoriasis. But in other countries, the skin rashes are strictly classified with the shape, form, size and region to break out. In many cases, the skin rashes are merely transformed by the conditions of skin and the regions to break out. If the skin rashes occur only on the thick skin areas, palms and soles of the feet, they may be called as palmoplantar pustulosis. If the rashes occur and develop on the thinner skin areas such as body and extremities, they may be called as psoriasis, or pustular psoriasis, even if the initiators and promoters to cause them are the same. Then the psoriasis-like rashes on the extrapalmoplantar areas are a subtype of pustular eruptions. This disease frequently accompanies various complications such as bone lesions, diabetes mellitus, IgA nephropathy, chronic thyroiditis and intestinal disorders. The incidence of the bone lesions is 100%, although the patient did not complain any pain. The main clinical symptoms of the bone lesions are severe chest pain extending to involve limited motion of the arms and shoulders. Also, severe backache and lumbago occur. In such a case, the disease is called as sternocostoclavicular hyperostosis. Then palmoplantar pstulosis may be regarded as a mild form of sternocostoclavicular hyperostosis and is not merely a skin disease but rather must be considered as one of the systemic diseases.

The incidence of the disease was one out of 500 persons at three institutions, respectively, which were located more than 350 km apart each other. The cause to break out this disease remained unknown, although local infection such as an inflammation of the tonsils or carious teeth, allergy derived from dental alloys or genetic abnormality had been proposed. This disease tends to aggravate despite various treatments with corticosteroids, nonsteroidal anti-inflammatory drugs, antibiotics, vitamin D, retinoid, immunodepressant drugs, PUVA radiation and/or partial resection of the affected bones for alleviation of severe chest pain, but all of these trials were without any relief and produced undesirable side effects.

Clinical characteristics

There are two major clinical characteristics in patients with palmoplantar pustulosis. One of them is many rice grain-sized sterile eruptions that develop on the palms and soles of the feet with epidermal thickening and immunoglobulin A (IgA) deposition in the surrounding areas of the eruptions. The other is pains over the sternum and clavicles, upper ribs and their joints, resulting in shrugging the shoulders like V-shaped or coat-hanger shoulder with ankylosis of the joints. Spurs and osteophytes are formed on the vertebrae. In advanced cases, the bone lesions rapidly worsen, irrespective of the severity of the eruptions on the palms and soles. Also, there is an intensive accumulation of isotope tracer on bone scintigrams, which are suggestive of ankylosing spondylitis. Mandiular sclerosis is observed in all patients.

The disease frequently runs in families, but it is not associated with any specific HLA antigen. The possible correlation between smorking habits and the occurrence of palmoplantar pustulosis and high prevalence of smorking habits were found in the patients. Smoking worsens the morbidity and markedly lessens the therapeutic effect of biotin, because it remarkably reduces serum biotin concentration and has a bad influence on the immune system.

Biochemical, metabolic and immune characteristics

The patients had metabolic abnormalities and subsequent immune dysfunction as a result of biotin deficiency. Biotin plays an important role as a coenzyme of various enzymes related to the metabolism of glucose, fatty acids and branched-chain amino acids. Thus, its deficiency causes serious metabolic abnormalities and adversely affects immune function. In fact, low serum biotin concentration, impaired glucose metabolism, reduced serum levels of fatty acids and abnormal composition of serum amino acids were observed in the patients. Other features of the patients include increased serum levels of 2-globulin and -globulin, an increased IgA level ,a marked increase of helper T lymphocytes, reduced numbers of suppressor T lymphocytes. ( These indicate abnormalities of immune function.) Also, an inverse correlation between helper T cells/suppressor T cells and serum biotin concentration was observed.

(This means that biotin deficiency is implicated in the occurrence of immune dysfunction.) In cases with severe bone lesions, there occurred an increase of Th1/Th2 in T lymphocytes.

In accordance with the concept, rats fed on a biotin-deficient diet showed similar skin and bone disorders, metabolic abnormalities and immune dysfunction. These findings suggested the possible therapeutic efficacy of biotin to the patients.

Treatment

As mentioned above, various treatments regimes had been proposed. Corticosteroid ointments are able to relieve transiently pustular eruptions, but fail to cause clinical, metabolic and immune improvement. Nonsteroidal anti-inflammatory drugs are of no effect ot correct the eruptions, although the patients might be temporally free of the chest pain or backache. Their long-use may be associated with rapidly developing arthropathy, because occurrence of immune dysfunction and inhibition of the synthesis of prostaglandins relating to bone remodeling. Antibiotics administration had been reported to be beneficial in the therapy of the eruptions in the patients, but the eruptions relapsed in a short time, even though the administration was continued. Other treatment regimes rapidly cause serious side effects. Also, the therapeutic effectiveness of these agents to the bone lesions could not be confirmed. Other trials rapidly cause serious side effects.

Oral administration of biotin to the patients alleviates chest pain after 1~2 weeks and almost eliminated within 4 weeks. Abnormal bone shadows on radiographs shows normal figures after 2 to 3 yearfs administration, if the bone damages are not advanced. Pustular eruptions disappear usually on the palms after 3 to 4 months and on the soles after 5 to 7 months. All of the biochemical and metabolic abnormalities were corrected soon. Immune dysfunction normalizes within 2 years. Complications, such as diabetes mellitus and IgA nephropathy, were also improved in a short time.

In the patients, frequent episodes of severe constipation or diarrhea were observed prior to the occurrence of the disease. Serum biotin concentration remained to be low and unchanged even after oral administration of the vitamin. Since biotin is mainly produced by microflora in the intestine and absorbed from the intestine into the circulation. It is, therefore, suggested that biotin deficiency may be attributable to the proliferation of gharmfulh microflora in the intestine to digest or to degrade the vitamin. However, supplementary administration of a probiotic agent, Clostridium butyricum Miyairii, to the biotin treatment significantly increased serum biotin concentration and maintained the concentration high enough to improve clinical manifestations and other disorders including complications, because the probiotic agent prevents the proliferation of the harmful microflora in the intestine and intensifies the therapeutic action of the vitamin with no evidence of hematological, renal and hepatic toxicity. Supplementation of other probiotic agents such as Lactobacillus showed poor therapeutic effectiveness to the biotin treatment, because the agents require much biotin for their proliferation. Addition of antibiotics to the biotin treatment significantly increased serum biotin concentration with a faster onset of clinical improvement. However, the beneficial response to the treatment was not long-standing. Serum biotin concentration again decreased to the basal level despite continued treatment, and therapeutic effectiveness wore off; presumably by not only inhibiting the development of gusefulh microflora to synthesize biotin but also promoting the proliferation of antibiotic-resistant gharmfulh microflora, resulting in poor therapeutic benefit.

Biotin administration produced no undesirable side effects

Conclusion

Patients with palmoplantar pustulosis had metabolic derangements of glucose and fatty acids as well as immune dysfunction derived from biotin deficiency, which led to abnormal manifestations of skin, bone and other tissues and organs. All of the clinical, metabolic and immune disorders were improved by biotin administration. These findings indicate that biotin deficiency was implicated in the outbreak and exacerbation of the disease and its complications. Supplementary addition of a probiotic agent to the biotin treatment intensified the therapeutic effect of the vitamin. Additionally, patients with psoriasis vulgaris, systemic erythematosus, atopic dermatitis or rheumatoid arthritis also had biotin deficiency with the subsequent metabolic abnormalities and immune dysfunction, and so the biotin treatment provided beneficial effects in the therapy of the diseases, as in the case of palmoplantar pustulosis.