Agranulocytosis from isotretinoin

Volume 18 Number 2, Part 1 February 1988

REFERENCES 1. Weiss SW, EnzingerEM. Spindle cell hemangioendothelioma--a low-grade angiosarcoma resembling a cavernous hemangioma and Kaposi's sarcoma. Am J Surg Pathol 1986;10:521-30. 2. Millard PR, Heryet AR. An irnmunohistochemieal study of factor VIII related antigen and Kaposi's sarcoma using polyclonal and monoclonal antibodies. J Pathol 1985; 146:31-8. 3. Nadji M, Morales AR. Immunoperoxidase techniques-a practical approach to tumor diagnosis. Chicago: ASCP Press, 1986. Agranulocytosis from isotretinoin

To the Editor: Since its development as a potent medication for cystic acne, isotretinoin has been a source of numerous side effects. One of the adverse effects known since early days of research with isotretinoin is leukopenia. In my experience, however, such a complication has been infrequent and relatively mild. This communication discusses a notable exception: a patient with granulocytopenia so severe that agranulocytosis was imminent.

Case report, The patient was a 16-year-old boy with pustulocystic acne that was unresponsive to treatment with tetracycline, erythromyein, minocyeline, and trimethoprimsulfamethoxazole. He denied taking any drugs other than those prescribed for his acne. Weighing 64 kg, he was started on isotretinoin 40 mg twice a day (1.25 mg/kg). All baseline laboratory data showed normal findings. The patient developed dry lips and extreme dryness of his face but had no other symptoms. At the end of the third week of therapy the dosage of isotretinoin was decreased to 40 mg a day (0.63 mg/kg) because of elevation of some of the liver enzymes: his alanine aminotransferase (ALT) was 56 U/L and his aspartate aminotransferase (AST) was 89 U/L (normals, 0-46 and 0-41 U/L). By week 6 isotretinoin dosage was restored to 40 mg twice daily, as the liver enzymes had returned to normal levels. During the eighth week of therapy the patient was noted to have a granulocytopenia of 33% of a total white blood cell count of 3300/ram 3 and a total granulocyte count of 1089/mm 3. At week 9 the patient's white blood cell count was reported as 10,700, only 9% of which were granulocytes. As the granulocyte count was 963/mm 3, isotretinoin was discontinued. The next day his granulocyte count declined to 570/ram ~. The total white blood cell count was 8150, 7% of which were granulocytes. Amazingly, the patient was asymptomatic. At no time did he have fever or sore throat; although he complained of slight fatigue, he was never anemic. His hematocrit ranged from 39% to 46% and was usually 42% to 45%. Because the patient was coping so well with the drug reaction, his internist elected not to hospitalize him and not to perform a bone marrow aspiration.

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Within 3 days the granulocytes began to rebound: 18% of his 7500 white blood cells were neutrophils. Over the next 4 weeks the granulocyte count continued to rise until it reached normal levels. Acne attained near-clearing for 3 months after the treatment was discontinued and then relapsed. C o m m e n t . Agranulocytosis in general is thought to occur either as a result of direct action on bone marrow cell production by a drug or by immunologic destruction of granulocytes. There m a y be a genetic predisposition to metabolize certain drugs in a way that results in selective bone marrow suppression. In this case agranulocytosis may have been an idiosyncratic reaction, representing an abnormality in metabolism o f the drug so that suppression of myeloid precursors occurs. Typically there is no anemia or thrombocytopenia. Fever, either from the drug reaction or from infection, is common, as are sore throat, fatigue, and flulike symptoms. Death can result from inability of the patient to fight overwhelming infection. The only other report of profound granulocytopenia from isotretinoin is Friedman's. 1 Unlike m y patient, his patient had persistent granulocytopenia 35 weeks after stopping isotretinoin. Isotretinoin is known to cause numerous s y m p t o m s and laboratory abnormalities. Most patients learn to tolerate the dryness that occurs c o m m o n l y on the lips, face, eyes, and other parts of the body. Pruritus of the dry skin is common, and many patients interpret this mistakenly as evidence of an allergic drug reaction. Other side effects include dry nose, sometimes with nosebleed, reversible hair thinning, fragility of skin, skin infections (which are probably related to the increase in nasal carriage of staphylococcus), photosensitivity, onycholysis, headache, pseudotumor cerebri, decreased night vision, tinnitus, corneal opacities, fatigue, menstrual abnormalities, hepatotoxicity, and regional ileitis. The drug is highly teratogenic and should be used with extreme caution in women during the childbearing years. Laboratory abnormalities include high triglycerides, aberrant liver function tests, low hemoglobin, leukopenia, increased platelets, abnormal urinalysis, and hyperut4cemia. Hyperostosis is found on x-ray examination of some patients. This report is submitted to alert dermatologists to an uncommon, possibly catastrophic reaction to isotretinoin and to emphasize the importance of frequent clinical and laboratory monitoring of all patients treated with this drug.

Margaret Waisman, M.D. Baylor College of Medicine, Houston, TX 77098

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REFERENCE i. Friedman SJ. Leukopenia and neutropenia associated with isotretinoin therapy. Arch Dermatol 1987;123:293-4.

Clinical presentation of scabies in a nursing home population To the Editor: Human scabies is a c o m m o n derrnatosis whose areas of predilection are classically described as involving the interdigital web spaces, flexor areas of the wrists, extensor surfaces of the elbows, anterior axillary folds, breasts, umbilical area, genitalia, and buttocks. Recently I encountered a scabies epidemic in a nursing home for the elderly. The patients had lesions involving the trunk and extremities in a haphazard array. I believe the clinical presentation of scabies in the elderly represents a distinct subset caused by a multitude of host-parasite interactions. Case report. Thirty-two patients were involved in an epidemic that occurred in a high level care nursing home. All patients were white, and all were suffering from multiple systemic disorders. Twenty-nine of the thirty-two patients had been treated previously with topical steroids without significant change in symptoms or presentation. All thirty-two patients had involvement of the trunk; five patients had lesions scattered on the extremities. In addition, eight patients had papulopustules at the time of presentation, and one had a l-era hyperkeratotic plaque on the outer aspect of the arm. A clear linear burrow was seen in only one very debilitated patient. No site preference was noted in regard to involvement of the breasts, genitalia, elbows, or buttocks. The papulopustule was found to harbor the mite in three of four epidermal shave biopsies performed. Some of the patients had involvement of the volar aspects of the wrists, web spaces of the hands, or genitalia. Lindane was elected as the mitocide. Lindane 1% lotion was applied from the neck down, left on for 8 hours, and repeated in 1 week. All signs and symptoms of the eruption abated within approximately 2 weeks, except in two patients who required a third treatment. Among the support staff, several members were infected. The clinical presentation in these patients was more classic in distribution, with a positive scraping for Sarcoptes scabiei noted on the web space of one individual. However, the most common diagnosis was acrophobia. In these cases, if the individual had no close contact with direct patient care, reassurance and bland emollients were prescribed. Four months after treatment no recurrence of the epidemic had been noted.

Discussion. Treatment o f a scabies epidemic in a nursing home requires intense dermatologic intervention. Partial treatment of the high-risk and moderaterisk groups is d o o m e d to failure. Close coopera-

Fig. 1, Excoriated patches noted on anterior aspect of chest.

tion of the entire support staff is critical for complete success. In the elderly patients studied, several interesting features emerged. A higher incidence of infection was noted in the patients as opposed to the support staff. This probably reflects an altered inflammatory response in the elderly, as well as racial differences; many of the support staff are Negro. z'3 Of particular interest was the distribution of the lesions, as shown in Fig. 1. A similar epidemic has been reported with these unusual and atypical f e a t u r e s . 4 It is my position that this presentation is not "atypical" but represents the true presentation of scabies in the elderly. The adult female S. scabiei walks a brisk 2.5 cm per minute looking for an ideal site to burrow. 5 As the ultrastructure of the stratum corneum changes with aging, it is of little surprise that the adult organism and its immature larvae and nymph respond to the changing topography. Some of these changes include an alteration in comeocyte shedding and an increase in stratum corneum renewal time. 6 Surface lipid changes are also known to O c c u r . 7 Other epidermal changes are a progressive uniformity of the epidermal undersurface, with a subsequent loss of epidermal undulations. These observations have been noted in the lower abdomen, areolae of the breasts, and genitalia of women. In the extreme elderly, frank uniformity is found, with the undersurface o f the epidermis completely flattened, s This uniformity of skin topography, along with changes in the stratum corneum associated with aging, may reflect in the site specificity acceptable to the mite. Scabies presents differently in the extreme elderly