Isotretinoin-induced thrombocytopenia

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Isotretinoin-induced thrombocytopenia To the Editor: Isotretinoin (Accutane) has revolutionized therapy for severe recalcitrant cystic acne. Dermatologists are well aware o f many clinical and laboratory adverse reactions that m a y be associated with this drug. Because isotretinoin is still a relatively new drug, dermatologists should be alert for possible unreported side effects. We report a case of profound thrombocytopenia secondary to isotretinoin therapy for cystic acne. A literature review revealed only one reported case. 1 Hoffmann-La Roche was unaware of any other cases and thrombocytopenia is not listed as a side effect in the package insert. Case report. A 15-year-old Hispanic adolescent in good health on no medications was seen for severe noduloeystic acne. Multisystem chemistry profile, complete blood cell count, and platelets (300,000/mm 3) were all within normal limits and the patient was started on isotretinoin, 60 mg (1 mg/kg) per day, on Dec. 24, 1986. The patient was seen on Jan. 7, 1987, tolerating isotretinoin well and complaining only of cheilitis. Repeat chemistry profile and complete blood cell count were again within normal limits, but platelets were 24,000/mm ~, confirmed by hand count. Isotretinoin was discontinued and the platelet count steadily returned to normal at 328,000/mm ~by Jan. 19, 1987. The patient did not develop signs or symptoms of thrombocytopenia. The patient was rechallenged with 60 mg of isotretinoin on Jan. 25, 1987. On Jan. 26, 1987 the platelet count dropped to 52,000/mm 3 while the complete blood cell count remained within normal limits. A platelet antibody test was positive at that time. Once again, the platelet count steadily increased to normal limits (275,000/mm 3) on Feb. 4, 1987 (Fig. 1). The complete blood cell and platelet counts were again within normal limits on Feb. 11, 1987.

Discussion. Isotretinoin has been shown to induce a number o f adverse laboratory reactions. Approximately 25% of patients develop elevated serum triglycerides while approximately 40% develop elevated sedimentation rates. Decreases in white blood cell counts, decreases in red blood cell parameters, elevated platelet counts, white cells in the urine, and increased alkaline phosphatase, aspartate transaminase (AST; SGOT), alanine transaminase (ALT; SGPT), gamma glutamyl transpeptidase (GGTP), or lactic dehydrogenase (LDH) are seen in 10% to 20% of patients. Less than 10% o f patients develop proteinuria, microscopic or gross hematuria, elevated creatine phosphokinase (CPK), uric acid, or fasting blood sugar. Thrombocytopenia is generally regarded as a platelet 838

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PLATELET count x l O 3 per rnm 3 330320310300290280270260250240230 220210200190180170" 180150140" 130120110100 9 9080" 70" 60" 5040" 30. 20" 10"

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DAYS ~ 2 i 6 h 1012 ~416 18202224282830123436384042 BEGIN ACCUTANE t6Omg/d)

DISCONTINUE ACCUTANE

RE-CHALLENGE WITH ACCUTANE ( 6 0 m g - o n e dose)

Fig. 1. Patients ~ pIatelet counts over time. Treatment with isotretinoin (Accutane) indicated by arrows.

count less than 100,000 mm 3 when bleeding after trauma or surgery may occur. Spontaneous bleeding rarely occurs until the platelet count falls to below 40,000 mm ~. Spontaneous bleeding is c o m m o n when the platelet count falls to 10,000 to 20,000 m m 3 and is often severe below 10,000 mm3. 2 A number of drugs are known to cause thrombocytopenia due to a hypersensitivity reaction. 3 In this reaction it is presumed that an antigen (drug)-antibodyplatelet membrane complex is formed, causing destruction of platelets. 4 The platelet antibody test is usually positive in drug-induced thrombocytopenia, as demonstrated in our patient. In summary, those prescribing isotretinoin should be aware o f the possible development of thrombocyto-

Volume 17 Number 5, Part 1 November 1987

Correspondence 839

penia, which, although very rare, is potentially fatal. Thrombocytopenia is known to occur rarely with etretinate thei'apy, so it makes sense that it may potentially occur with other retinoids such as isotretinoin.

Timothy M. Johnson, M.D., and Ronald P. Rapini, M.D. The University of Texas Medical School Houston, TX 77030 REFERENCES

I. Hesdorffer CS, Weltman MD, Raftopoulos H, et al. Thrombocytopenia caused by isotretinoin. S Afr Meal J 1986;70:705-6. 2. Nossel HL. Platelet disorders. In: Issetbaeher KJ, Adams RD, Braunwalk E, et al, eds. Harrison's Principles of internal medicine. New York: McGraw-Hill, 1980:1555. 3. Miescher PA. Drug-induced thrombocytopenia. Semin Hematol 1973;10:311-25. 4. Shulman NR. A mechanism of cell destruction in individuals sensitized to foreign antigens and its implications in autoimmunity. Ann Intern Med 1964;60:506-21.

Recurrent erythema multiforme due to

Mycoplasma pneumoniae To the Editor: Erythema multiforme is a mucocutaneous disease with a wide spectrum of clinical findings. Erythema multiforme minor iepresents the mild, serflimited form as described by Hebra, while elajthema multiforme major refers to the more severe form classically known as Steveris-Johnson syndrome. ~ Jtecurrent oral erythema multiforme has been well documented? Cases of continuous erythema multiforme both mucosal 2 and cutaneous forms, s have also been reported in recent years. We report a case of recurrent erythema multiforme major with a unique distribution and persistent oral lesions that may represent continuous mucosal erythema multiforme. Case report. A 15-year-old male patient was admitted to Pitt County Memorial Hospital in January 1987 for his fourth episode of recurrent erythema multiforme over an 8-year period. Each episode was preceded by mild upper respiratory symptoms followed by fever and the appearance of vesicles on the oral mucosa after 6 or 7 days. From the history obtained concerning previous outbreaks, mucosal involvement was limited to the oral mucosa and conjunctivae with skin involvement confined to the genitalia. The patient also reported having mouth ulcers that were present almost constantly during the 3-year interval since the last outbreak of erythema multiforme. He had taken no medications prior to the onset of this episode and there was no history of medications

Fig. 1. Vesicles present oia the glans penis with numerous target lesions on the shaft of penis and scrotum.

used, including topical preparations at the time of previous outbreaks. Examination of the patient at the time of hospitalization (3 days after vesicles appeared on the oral mucosa) revealed an acutely ill adolescent with a temperature of 39~ C. There was extensive ulceration of oral mucosa, gingivae, palate, and lips, with further extension to the posterior aspect of the pharynx. Conjunctivae were injected bilaterally with numerous palpebral vesicles present. Severe urethritis with dysuria was present, and the patient could void only by sitting in warm water. Cutaneous findings were limited to the genitalia and consisted of numerous vesicles on the glans penis with characteristic target lesions on the shaft of the penis and scrotum (Fig. 1). The remainder of the physical examination showed normal findings. Pertinent laboratory findings included: white blood cell count, 18,400; herpes titer (indirect fluorescent antibody), negative (<1'.8); herpes culture from oral lesion, negative; bedside cold agglutinins, strongly positive; mycoplasma titers (complement fixation), acute, negative (< i : 8), convalescent, positive (l:128); chest x-ray film, normal. Lesional biopsy was not performed. Prednisone therapy (60 rag/day) was initiated. During the first 12 hours of hospitalization the vesicular lesions coalesced to form a bulla involving the entire glans penis. Periods of epistaxis (4-6/day) began on the second hospital day and continued for 4 days. Conjunctivitis became purulent on the second hospital day and cultures were positive for Staphylococcus aureus. Ophthalmic drops with dexamethasone, neomycin, and polymixin B were started. Development of new mucosal and cutaneous les ions ended on the third hospital day and clinical improvement was evident. The patient was discharged from the hospital after 6 days, with prednisone therapy continued until a follow-up examination 9 days later. Examination at the time of follow-up showed complete resolution of conjunctivitis with marked improvement of the oral lesions. There was no crusting of the mouth or nares.