Volume 22
`
`Number 2, Part 1
`February 1990
`
`10. Girardin E, Dayer JM, Paumer L. Cyclosporine for juve-
`nile dcrmatomyositis [Letter]. .1 Pediatr 1988;112:165-6.
`11. Mikatsch MJ, Bach J F, Cooradia HM, et a1. Cyclosporine-
`associated nephropathy in patients with autoimmune dis~
`eases. Klin Wochenschr 1988;66:43-7.
`12. Myers BD. Cyclosporine—associated chronic nephropathy.
`N Engl J Med 1984;311:699-705.
`
`Fumaric acid therapy for psoriasis: A randomized,
`double-blind, placebo-controlled study
`
`Wieke M. Nugteren-Huying, MD,a
`Jan Gerrit van der Schroeff, MD,a Jo Hermans, PhD,b
`and Dick Suurmond, MDa Ieiden, The Netherlands
`
`During the past few years, fumaric acid therapy for
`psoriasis has gained interest among Dutch and German
`patients. This treatment was empirically devised by the
`German chemist Schweclcendiek1 and further developed
`by the German physician Schz'ifer.2 Fumaric acid therapy
`is based on the following principles: (1) oral treatment
`with monoethyl and dimethyl esters of fumaric acid, (2)
`topical treatment with monoethylfumarate, and (3) a diet
`that forbids the consumption of nuts, spices, wines, and
`distilled products of wine. Because controlled studies have
`not been reported, we decided to investigate the clinical
`efficacy and side effects of fumaric acid therapy.
`
`Patients and methods. Thirty-nine psoriasis patients (12
`women and 27 men), ranging in age from 20 to 73 years (mean
`44 years), entered the study. The patients had to fulfill the fol-
`lowing criteria: (1) involvement of at least 10% of the body sur-
`face, (2) stable disease, (3) normal kidney and liver function, (4)
`no cardiac or gastrointestinal problems, and (5) no current
`pregnancy. The patients were randomly assigned to three
`groups. Group 1 was treated orally with emetic-coated tablets
`containing 120 mg dimethylfumarate, 87 mg calcium monoet-
`hylfumarate, 5 mg magnesium monoethylfumarate, and 3 mg
`zinc monoethylfumarate. Group 2 was treated orally with
`enteric—coated tablets containing 284 mg octyl hydrogen fuma-
`rate, 5 mg magnesium monoethylfumarate, and 3 mg zinc m0-
`noethylfumarate. Group 3 was given orally administered pla-
`cebo tablets. All tablets (provided by Fumapharm AG, Muri,
`Switzerland) had the same appearance, size, and color. The
`deuble-blind treatment lasted 16 weeks for each patient. The
`dosage schedule called for a gradual increase from one to six
`tablets daily. All patients received topical treatment with 5%
`salicylic acid in white petrolatum. From 2 weeks before treat-
`ment until the end of the study, no other antipsoriatic therapy
`was allowed. All patients were asked to follow strictly the dietary
`
`From the Department of Dermatology, University Hospital,8 and the
`Department of Medical Statistics, University of Leiden.b
`Reprint requests: J. G. van der Schroell, MD, Department of Derma-
`tology, University Hospital, PO. Box 9600, 2300 RC Leiden, The
`Netherlands.
`
`16/4/13804
`
`Brief communications 311
`
`guidelines associated with fumaric acid therapy (avoidance of
`nuts, spices wines, and distilled products of wine). Extent and
`activity of skin disease were assessed by estimating the percent-
`age of body surface affected with psoriasis and by scoring the
`degree of infiltration and scaling of the plaques (from 0, no in-
`filtration or scaling; to 8, very severe infiltration or scaling). The
`following laboratory investigations were performed: erythrocyte
`sedimentation rate; leukocyte differential count; and determi-
`nation of levels of hemoglobin, hematocrit, urea, creatinine,
`AST (SGOT), ALT (SGPT), lactate dehydrogenase, alkaline
`phosphatase, gamma glutamyltransferase, total bilirubin, glu-
`cose, and protein. Urinalysis for levels ofglucose and protein and
`24-hour creatinine clearance rate were also performed. Statis-
`tical analysis was performed with the Kruskal-Wallis test,3 a
`nonparametric analysis of variance.
`
`Results. At baseline no significant differences were
`found among the three groups with regard to sex ratio,
`age, type and duration of psoriasis, extent and severity of
`the skin lesions, and preceding antipsofiatic therapy. Of
`39 patients, 34 completed the study. In the patients
`treated with the combination of monoethyl fumarate and
`dimethylfumarate (group 1, n = 12), the mean percent-
`age of the body surface affected with psoriasis was
`reduced from 21% (at baseline) to 6.7% after 16 weeks.
`This effect was significantly different from the results ob-
`tained in patients of groups 2 (n = 10) and 3 (n= 12)
`(p < 0.01). After 16 weeks of treatment, the mean scores
`for infiltration and scaling were significantly lower in pa-
`tients in group 1 than those in groups 2 and 3 (p < 0.01 ).
`In group 1, six patients showed complete clearance and
`three showed improvement. In group 2 no such results
`were observed, and in group 3 only one patient showed
`improvement.
`The main side effects of the treatment in group 1 were
`flushing (12 patients), diarrhea (13), fatigue (7), and
`nausea (6). One patient became ill as a result of renal in-
`sufficiency. In group 2 diarrhea was the main side effect
`(12 patients). Laboratory investigations showed a tran-
`sient rise in liver function tests in group 1 (eight patients)
`and in group 2 (four). The patient in group 1 in whom a
`reversible renal insufficiency developed showed a rise of
`serum creatinine up to 238 pmol/ L and a 51% reduction
`in the 24-hour creatinine clearance rate. Other abnor-
`
`malities observed in group 1 were transient eosinophilia
`(five patients) and lymphopenia (four).
`Discussion. The results of this study show that oral
`treatment with tablets containing a combination of dim-
`ethyl fumarate and monoethylfumarate may be effective
`in the treatment of psoriasis. This treatment may provide
`a new alternative for patients with severe psoriasis. The
`drawback of fumaric acid therapy may be its side effects.
`Carefully administered,
`low-dose regimens, however,
`may overcome this problem. Further studies with regard
`to the treatment’s long-term therapeutic effects, toxicity,
`and mode of action are needed.
`
`Sawai (IPR2019-00789), EX. 1029, p. 001
`
`Sawai (IPR2019-00789), Ex. 1029, p. 001
`
`

`

`312 Brief communications
`
`REFERENCES
`
`l. Schweckcndiek W. Heilung von Psoriasis vulgaris. Med
`Monatsschr 1959;13:103-4.
`2. Sehz’ifer GN. Fumarséturc lindert die Schuppenfiechte. Se-
`lecta 1984;15:1260—1.
`3. Glantz SA. Primer of biostatistics. New York: McGraw-
`Hill, 1981;269-31l.
`
`Pimou’de in delusions of parasitosis
`
`J. Timothy Damiani, MD,a Franklin P. Flowers, MD,b
`and Douglas K. Pierce, MDb Cross City and
`Gainesville, Florida
`
`Delusions of parasitosis is a type of monosymptomatic
`hypochondriac psychosis (MHP). In MHP the patient’s
`sole complaint focuses on a single delusion. For some, the
`delusion may be their belief in the abnormal shape of their
`face; for others it may take the form of a fantasized odor
`emitted from their body. Dermatologists frequently deal
`with patients who bring a jar full of debris and claim that
`these are creatures that infest their scalp, limbs, or orifices
`(Fig. 1). What seems to set these patients apart is that
`beyond their delusion they are normal, or at least within
`acceptable bounds.
`
`Case report. A 71-year-old white woman had an 8-month
`history of burning and itching of the scalp. She had been treated
`without success with antibiotics and shampoos. Physical exam-
`ination revealed keratotic papules and a few areas of patchy
`alopecia. Results of laboratory studies revealed no significant
`abnormality. Prurigo nodularis was diagnosed and the patient
`was treated with oral doxepin, 25 mg, taken at bedtime.
`Shortly thereafter, she reported “something crawling under
`my scalp" and was convinced thatsome bugs were either “dead"
`or “moving around” on her scalp. The doxepin was discontinued
`and she was treated with oral pimozide, 1 mg, twice a day. In-
`one month the patient was much improved although she still had
`a burning sensation of the scalp. The dosage of pimozide was
`increased to 2 mg twice a day and the complaints subsided. She
`discontinued her medication at 6 months and the delusions re-
`
`turned. Pimozide, 2 mg, twice a day was given again and the
`patient’s symptoms were under control for an additional year.
`
`Discussion. Pimozide is approved for the treatment of
`chronic schizophrenia and Gilles de la Tourette syndrome
`but has also been found effective in the treatment of
`
`MHP.“6 In addition, Duke5 found that patients who had
`postherpetic neuralgia with neurotic excoriations, symp-
`toms of delusions of parasitosis, or both also benefited
`
`From the US. Public Health Service, Cross City,“ and the Division of
`Dermatology & Cutaneous Surgery, University of Florida College of
`Medicine, Gainesville.”
`Reprint recruests: Franklin P. Flowers, MD, Division of Dermatology,
`University of Florida, Box J-277, .lHMHC, Gainesvillc, FL 32610.
`16/1/13805
`
`Journal of the
`American Academy of
`Dermatology
`
`
`
`Fig. 1. Patients with delusions of parasitosis may bring
`in assorted scale and debris to “prove that they are
`infested.”
`
`from pimozide. Only patients with severe pain and no
`other complaint did not benefit from the drug.4 However,
`Hamaun7 observed pimozide to be effective in a case of
`onychotillomania.
`Contraindications to pimozide include vascular insuf—
`ficiency of the central nervous system, blood dyscrasias,
`Parkinson’s disease, prolonged congenital QT syndrome,
`cardiac dysrhythmias, or drugs that prolong the QT
`interval. Pimozide also reduces the convulsive threshold
`
`and should be used with caution in persons with epilepsy.
`Its safety has not been established in children or pregnant
`women.
`
`Acute and transient adverse effects include extrapyra-
`midal reactions (restlessness, dystonia, parkinsonism).
`Tardive dyskinesia is a serious reaction; elderly patients
`receiving high—dose therapy are at greatest risk. This may
`be irreversible after long-term use of the drug. However,
`fine vermicular movements of the tongue may be an early
`sign of tardive dyskinesia; if the medication is stopped at
`that time, the syndrome may disappear. Electrocardio»
`graphic changes have been reported with prolongation of
`QT interval, T-wave changes, and the appearance of
`U waves. Sudden unexpected deaths and grand mal sei-
`zures have occurred at doses greater than 20 mg/day.
`Dosage, after a baseline electrocardiogram, should be
`begun at 1 to 2 mg/day in divided doses. Dosage may be
`increased every other day; however, doses greater than 0.2
`mg/kg/day or 10 mg/day are not recommended. In no
`case should the dose exceed 0.3 mg/kg/day or 20
`mg/day.3
`Gould and Gragg9 recommended that, in a patient who
`has delusions of parasitosis, the role of the dermatologist
`should be to rule out other causes of pruritus that may
`contribute in some way to the delusion. Any attempt at
`referral to a psychiatrist will be often resisted. In fact, it
`may even alienate a patient who has already chosen the
`type of treatment he or she wants or will accept.
`Munro2 recommends that all patients with diagnoses
`
`Sawai (IPR2019-00789), EX. 1029, p. 002
`
`Sawai (IPR2019-00789), Ex. 1029, p. 002
`
`