A case of psoriasis pustulosa. Treatment with potassium. iodide and measurement of oxygen intermediates

Transcription

1 s-11 A case of psoriasis pustulosa. Treatment with potassium iodide and measurement of oxygen intermediates Kyoko Nakajima, Jinro Komura, Setsuko Nishijima, Yasuo Asada and Yukie Niwa* Department of Dermatology, Kansai Medical University, Moriguchi, Osaka, and *Niwa Institute for Immunology, Kochi, Japan Keywords : psoriasis pustulosa, potassium iodide, oxygen intermediates Abstract A female patient with psoriasis vulgaris developed pustularform eruptions while being treated with thiamazole for her hyperthyroidism. The exudative pustular eruptions rapidly subsided with the use of oral potassium iodide. The measurement of oxygen intermediates showed that the generation of superoxide anion (0i) and hydroxyl radical (OH') by polymorphonuclear neutrophils in the peripheral blood was high at the peak of the pustular attack. Introduction A woman who had psoriasis lesions for about eight months suddenly developed generalized pustulation which was found to be provoked by an anti-thyroid drug, thiamazole (1-methyl-2- mercaptoimidazole). Although potassium iodide is known to induce generalized pustulation in psoriasis patients, this opportunity was used to examine whether the drug can change the course of pustulation, since potassium ioidide has recently been reported to be effective in the acute phase of erythema nodosuml, 2), and we experienced a case of acute generalized pustular bacterid in which not only erythema nodosum lesions but also pustules promptly subsided with the use of the drug3'. Also the polymorphonuclear neutrophil (PMN) -derived oxygen intermediates, such as superoxide anion (0), hydrogen peroxide (H202) and hydroxyl radical (OH') were measured before and after the taking of potassium iodide, since the drug has recently been shown to interfere with these oxidants in an in vitro experiment4). Case Report A 21-year-old woman had an eight month history of psoriasis vulgaris involving the scalp, patellar and elbow regions. Her condition had been well controlled by topically applied corticos- Supplement to J. Kansai Med. Univ., Vol. 36, Dec. 1984

2 S 12 teroids. Two months prior to her visit to our clinic, she was diagnosed as having hyperthyroidism and was given an anti-thyroid drug, thiamazole. The dose was 15 mg three times a day at the beginning but was reduced to 10mg three times a day at the time of the pustular attack. About one month after starting this new medication, she suddenly noted small grouped pustules scattered on the psoriatic lesions of the patellar and elbow, lesions, and also on the palms. On October 22, 1981, the patient was seen at our clinic and was subsequently hospitalized. On admission, she was afebril but showed arrhythmia and tachycardia. Her eyes were slightly exophthalmic, and goiter was noticed. In the skin, scattered pustules were noticed on the old psoriasis plaques of the patellar and elbow regions. Also, new erythmatous patches with pustules were seen on the forearms and legs. On the right forearm, pustules with erythema were seen as KObner reaction. On the back, several isolated pustules were noted. Her palms were diffusely erythematous with many pustules, but soles showed only erythema. No oral lesions were seen. Nails were intact. Laboratory studies. A complete blood cell count was : hemoglobin 12g/dl ; hematocrit, 34. 8% WBC, 6900/cu mm with 13% eosinophils, 10% band forms, 58% segment forms, 16% lymphocytes, 3% monocytes ; ESR, 11mm/hr ; platelets, 146, 000/cu mm. Serum enzyme studies showed high levels of alkaline phosphatase (643 IU/1), GOT (52 IU/1), GPT (47 IU/1), LAP (110 RI/1) and r GTP (48 IU/1). The level of calcium was reduced to 3. 6 meq/1 (normal, 4. 3 to 5. 2 meq/1) and that of phosphate was elevated to 4. 8 meq/1 (normal, 2. 7 to 4. 3 meq/1). Other blood chemistry tests revealed normal levels of BUN, creatinine, uric acid, bilirubin and lactic dehydrogenase. Total protein was 4. 1 g/dl with albumin 60. 7%, a1-globulin 3. 5%, a2 8. 6%, /911. 8%, and r 15. 1%. The levels of the immunoglobulins IgG, IgM, IgA and IgE were within normal limits. HLA phenotypes were A2, AW24, BW51 and BW60. Histopathology. The pustules from the knee and from palm were biopsied. Hematoxin-eosin stained section showed that the pustule from the knee was Kogoj's spongiform while that from the palm was a pustulosis palmaris et plantaris-type, intraepidermal, unilocular one Course. At the time of consultation, the patient took thiamazole 5mg three times a day. For several days after admission, new isolated pustules appeared on the trunk, and there were also grouped pustules on the soles. Oral potassium iodide was tried, and for three days, 100mg three times a day was given. As there seemed to be no adverse effect, the dose was increased to 300mg three times a day. This dose was continued for one week, then 200mg three times a day for two weeks. On the fourth day of admission, thiamazole was decreased to 5 mg twice a day and discontinued nine days later. Coinciding with the increase of potassium iodide and the decrease of thiamazole, the erythemtous pustular lesions started to improve. No new pustules appeared, and the exudation tendency stopped. In several days, new lesions almost cleared

3 S 13 leaving only old psoriatic plaques. During hospitalization, guaiazulene ointment was applied daily. Five weeks later, at the time of discharge, tests showed that liver function was almost within normal limits, and the thyroid function was controlled without taking thiamazole. An attempt to induce pustular lesions using thiamazole was carried out. The patient took 5mg a day for three consecutive days. On the fourth day, localized, small grouped pustules appeared on the right palm. Potassium iodide was administered at a dose of 600mg, and the eruption disappeared in four days. Two years later, she still complained of localized psoriatic lesions. She underwent subtotal resection of the thyroid gland. Measurement of oxygen intermediates Measurement of oxygen intermediates were performed on two occasions at the time of admission and 10 days after stopping the use of potassium iodide according to previous literature4,. On October 22, 1981, the values were markedly elevated ; O : 1. 18±0. 095n mol (P<0. 01, compared to healthy controls), H202 : ± 0. 62p mol (O. 01<P<0. 05), OH 21. 2±1. 03p mol (P<0. 01), chemiluminescence : 287, 800 ± 1, 234 cpm (0. 01<P<0. 05) (Table 1). On Novemb er 28, 1981, the levels were lowered almost to the control values ; O : O. 59 ± n mol. H202 : ± p mol, OH , chemiluminescence : 205, cpm (all : P<0. 05, compared to healthy controls) (Table 1). The levels of lysosomal enzymes such as /3- glucuronidase, lysozyme and lactate within normal limits (Table 2). dehydrogenase determined twice on the same day were Table 1 Generation of oxygen intermediates by PMNs from patient and controls stimulated with opsonized zymosan Supplement to J. Kansai Med. Uuiv., Vol, 36, Dec. 1984

4 S 14 Table 2 Lysosomal enzyme levels in the Patient and Controls Adverse cutaneous reactions to iodides include acneiform eruption, erythema nodosum, eyelid edema, fixed eruption, follicular pustules and purpure. On the other hand, it is reported that in erythema nodosum potassium iodide promptly relieves subjective symptoms, auch as tenderness, joint pain and fever, and causes substantial improvement of the eruptions in a few days", 2) In the present patient, by increasing the dose of potassium iodide to 900mg per day, the tendency of exudation and pustulation stopped, and the skin lesions became markedly dry in several days. Similar effects were also noticed when the pustular lesions were provoked by thiamazole. The mechanism by which potassium iodide exhibits antiinflammatory activity in erythema nodosum is explained as follows') : the drug concentrates in the granulomatous tissues and causes heparin released from mast cells which in turn suppress delayed hypersensitity reactions. Recently, Miyachi and Niwa4) measured PMN-derived oxygen intermediates (0i, H202 and OHS) in healthy individuals. When the therapeutic doses of potassium iodide were added to the in vitro oxygen intermediates assay system, it was found that the generation of H202 and OH was significantly suppressed. The authors considered that this fact may explain the effectiveness of potassium iodide. Superoxide anion (0i) generated on PMN cell membranes as a result of stimulation by soluble or particulate materials dismutates spontaneously or enzymatically to form potent oxidants, such as H202, OH and singlet oxygen (102). These oxidants not only provide PMNs with an important mechanism for bactericidal activity but also could damage tissues in inflammatory site7, 8). It is suggested that infliction of tissue damage might occur through destruction of thiol groups, through peroxidative decomposition of essential membrane-associatted fatty acids and through reaction with nucleic acid bases7). In the present patient, the generation of O and OH by PMNs in the peripheral blood was fairly high at the peak of pusular attacks and these returned to normal after the taking of potassium iodides. The levels of lysosomal enzymes, including j3-glucuroninase, lysozyme and lactate dehydrogenase measured at the same time, were all within normal limits. It is possible that PMNs infiltrated into epidermis liberate oxidants and

5 S 15 cause locally exudative inflammatory changes, and these changes may be prohibited by potassium iodide. The course of generalized pustular psoriasis varies. It can be divided into two contrasting groups9). In the first, the pre-pustular phase of psoriasis is long, the episode is clearly precipitated by extraneous factors and the prognosis is often good, psoriasis having a tendency to return to an ordinary pattern. In constrast, in the second group, the generalized pustulation is apparently spontaneous, and the outlook is worse, there being less tendency to spontaneous resolution. Whereas, in the latter group, methotrexate is the drug of choice and systemic corticosteroids may be indicated as a life-saving necessity, in the former the use of corticosteroids is not indicated as this may only perpetuate the illness. The initial, expectant treatments should consist of bland topical or weak corticosteroid applications' ). In the present patient, there was only one pustular attack, and the psoriasis lesions continued. The pustular attacks might have recovered spontaneously anyhow, but it is felt that by using potassium iodide erythematous exudative changes rapidly improved and also pustules tended to disappear. Thus, potassium iodide could be a drug of choice in the above-mentioned first group of patients. It may possess two effects (con' 1) and pro) for psoriasis and pustulation in the same way as it has two effects for erythema nodosum. References 1) Schulz, E, J. and Whiting, D. A. : Treatment of erythema nodosum and nodular vasculitis with potassium iodide. Br. J. Derm., 94, 75-48, ) Horio, T., Imamura, S., Danno, K. and Ofuji, S. : Potassium iodide in the treatment of erythema nodosum and nodular vasculitis. Arch. Derm., 117, , ) Futamura, S., Nishijima, S., Kusunoki, K., Asada, Y. and Uemura, K. : A case of acute generalized pustular bacterid with erythema nodosum. Skin Res., 25, , ) Miyachi, Y. and Niwa, Y. : Effect of potassium iodide, colchicine and dapsone on the generation of polymorphonuclear leukocyte derived oxygen intermediates. Br. J. Derm., 107, , ) Niwa, Y., Miyake, S., Sakane, T., Shingu, M. and Yokoyama, M, : Auto-oxidative damage in Behcet's disease. Endothelial cell damage following the elevated oxygen radicals generated by stimulatedneutrophils. Clin. Exp. Immunol., 49, , ) Domonkos, A. N., Arnold, H. L. Jr. and Odom, R. B. : Andrews' diseases of the skin. 7th Ed., Saunders, Philadelphia 1982, p ) Johnston, R. B. Jr. and Lehmeyer, J. E. : Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease. J. Clin. Invest., 57, , ) Sedgwick, J. B., Bergstresser, P. R. and Hurd, E. R. : Increased superoxide generation by normal granulocytes incubated in sera from patients with psoriasis. J. Invest. Derm., 76, , ) Ryan, T. I. and Baker, H. : The prognosis of generalized pustular psoriasis. Br. J. Derm., 85, , ) Baker, H. and Wilkinson, D. S. : Psoriasis ; in Rook, Wilkinson and Ebling Textbook of dermatology Supplement to J. Kansai Med. Univ., Vol. 36, Dec. 1984

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