1112 Brief communications piroxicam is unusual. However, patients who use piroxicam often also use additional analgesic drugs. Therefore some cases in which fixeddrug eruption has been caused by piroxicam may have been missed because the other drugs have been blamed. When cautious provocation is performed, as described by Kauppinen.l? a mild reaction is produced. Topical provocation can replace systemic testing with phenazone derivatives but with other drugs the results are not reliable," REFERENCES 1. Pasricha JS. Drugs causing fixed eruptions. Br J Dermatol 1979;100:183·5. 2. Kauppinen K, Stubb S. Fixederuptions: causative drugs and challenge tests. Br J Dermatol 1985;112:575-8. 3. StubbS, Alanko K, Reitamo S. Fixed drug eruptions: 77 cases from 1981 to 1985. Br J DermatoI1989;120:583. 4. Alanko K, Stubb S, Reitamo S. Topical provocation of fixed drug eruption. Br J Derrnatol 1987;116:561-7. 5. Bigby M, SternR. Cutaneous reactions to nonsteroidal anti-inflammatory drugs: a review. J AM ACAD DER.>.fATOL 1985;12:866-76. 6. Bertail M-A,Cavelier B, Civatte J. Reaction au piroxicam (Feldene). A type d'ectodermose erosive pluri-orificielle, Ann Dermatol VenereoI1982;109:261-2. 7. Torres H, MartiMR.Urticaria agudapor Piroxicam. Med Cutan Ibero Lat Am 1982;10:351-2. 8. Kauppinen K, Stubb S. Drug eruptions: causative agents and clinical types. Acta DerrnVenereal 1984;64:320-4. 9. Savin JA. Drugs causing fixed eruptions. Br J Dermatol 1970;83:546-9. 10. Kauppinen K. Rational performance ofdrug challenge in cutaneous hypersensitivity. Semin Dermatol 1983;2:22730.
Acute depression from isotretinoin Pamela L. Scheinman, MD, * Gary L. Peck, MD, David R. Rubinow, MD, John J. DiGiovanna, MD, Donita L. Abangan, MD, and Paula D. Ravin, MD
Bethesda, Maryland A spectrum ofcentral nervoussystem sideeffects, similar to that observed with the hypervitaminosis A syndrome induced by retinyl esters has been described with other natural and synthetic retinoids.' For example, depressive symptoms, such as crying spells, malaise, and forgetfulness, have been noted in some patients receiving isotretinoin.e The depression subsides with discontinFrom the Dermatology Branch, National Cancer Institute, National Institutes ofHealth. Reprint requests: Gary L. Peck, MD, Dermatology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Room 12N238, Bethesda, MD 20892. "'Now at the Department of Dermatology, University of Rochester School ofMedicine, Rochester, N.Y. 16/4/20231
Journal of the American Academy of Dermatology
uatiorr' and recurs with reinstitution of therapy." In this article we describe seven patients in whom severe depression developed during isotretinoin therapy.
Material and methods. Seven patients, five women and two men, reported major depressive symptoms during treatment with oral isotretinoin. They participated in clinical trials of isotretinoin involving approximately 700 patients with cystic acne, psoriasis, cutaneous disorders of keratinization, or basal cell carcinoma. Patients involved in clinical trials were volunteersfrom whom informed consent was obtained. The diagnosis of depression wasmadeon the basisof the patients' spontaneous report of the recent onset of the cardinal symptoms of depression.i The diagnosis of a major depressive disorder was confirmed bya psychiatrist (D. R. R.) in the three patients who were interviewed during their depression. The rapid resolution of depression afterdiscontinuation of isotretinoin precluded a psychiatric interview while the remaining four patients were symptomatic.
Results. In five of the seven patients in whom depressivesymptoms developed during treatment with isotretinoin, the symptoms developed during the first course of therapy. The other two previously had one or two courses of treatment with isotretinoin without depression (Table I). The patients in this study voluntarily reported symptoms characteristic of a major depressive episode' during treatment with isotretinoin (Table II). The severity of these symptoms interfered with normal functioning in most patients. In each patient isotretinoin therapy was discontinued when depressive symptoms were reported. All symptoms resolvedwithin 2 to 7 days after discontinuation of the drug. Although two patients had a history of mild depression, none required medication or hospitalization. The depressiveepisodes during isotretinointherapy in patients 1 and 6 were much more severe than those previously experienced. During treatment in these two patients, fatigue, inability to concentrate, lack of motivation, forgetfulness, and crying spells also developed. In one patient (No.5) the relationship of depression to isotretinointherapy was confirmedby rechallenge, In this patient symptoms developed during the tenth week of the initial course of isotretinoin (0.7 mg/kg/day). The depression resolved within 7 days after discontinuation of the medication. Ten weeks later treatment was resumed at 10 mg/day and after a month increased to 20 rug/day (0.3 mg/kg/day). The depression reappeared during the third month of this second course of therapy. Discontinuation of isotretinoin was again followed by rapid disappearance of depressive symptoms. Three of seven patients also had headache during their depression. In one patient the headaches occurred daily and were not relieved by medication (acetaminophen). Headaches in all patients resolvedafter cessation of ther!ipy.One patient had dizzinessthat also resolved promptly.
Volume 22 Number 6, Part 1 June 1990
Briefcommunications 1113
Table I. Characteristics of therapeutic courses of isotretinoin associated with depression Age (yr)/
Time to onset"
Diagnosis
Sex
(wk)
mg/day
Acne Acne Acne Psoriasis Acne
31/M 22/F 24/F 26/F
8 10 14 47
80 40 40 60
10 8-12
40 17 40 40
Patient
No.
1 2 3 4 5
BCC Acne Mean
I
No.of
47/F
7
261M
6 14
32
Time to
c\eart
prior mg/kg/day
courses
Headache
1.3
2:\:
0.1 0.1 1.1
0 0
+
1§
+ +
42jF
1st course 2nd course 6 7
Mean dosage
(days)
7 7 2 4
0.1
0
OJ
1
0.5 0.5 0.1
0
2
0
7
7 2
+, Present; -, absent; Bee.
basal cellcarcinoma. ·Time to' presentation of depression after initiationof therapy. t After discontinuation of therapy. :j:Mean dosage for first coursewas 0.3 rng/kg/day for 16 weeks; meandosageforsecond coursewas2 mg/kg/day for 26 weeks; interval between second and third course was 3.5 years. §Mean dosage for first course was 2,4 mg/kg/day; interval between first and second course was 5 years.
Funduscopic examination in four patients during the depressive episode failed to identify papilledema. At the time ofpresentation none of the patients were taking other medications that have been implicated in the development of pseudotumor cerebri. 6 Discussion. The results of this study suggest that depression is a rare side effect of isotretinoin that was spontaneously reported in 1 of approximately 100 patients. In these patients the onset of depression was related to neither dosage nor time. Irrespective of dosage, all depressive symptoms rapidly resolved within 1 week of cessation of medication. On the basis of the patients' psychiatric history, the development of a major depressive episode in all seven patients in this study most likely represents an idiosyncratic side effect of isotretinoin rather than a predictable effect in a subset of patients predisposed to develop major depressions. Treatment with retinoids can produce benign intracranial hypertension (BIH).l,7 BIH also has been reported after the resolution of a major depressive syndrome.f Nonetheless, depression was reported to precede by 1 year the diagnosis of pseudotumor cerebri in one patient with chronic hypervitaminosis A.9 BIH is characterized by (1) increased intracranial pressure, (2) normal cerebrospinal fluid composition, (3) normal radiographic studies, and (4) symptoms and signs that result from the increased intracranial pressure, such as headache, visual disturbances, and papilledema.f Thus the symptoms of headache and depression observed in this study could suggest a diagnosis of BIll. However, the rapid resolution of the depression after discontinuation of isotretinoin in all patients and the negative funduscopic examination in four patients argue against a diagnosis of BIR. There-
Table II. Symptoms observed during isotretinoin treatment in seven patients developing a major depression No. of patienls with symptom
Fatigue (increased sleep, loss of energy) Irritability Decreased concentration Sadness Crying spells Loss of motivation (school, social contacts) Forgetfulness Suicidal ideation Anhedonia Abnormal dreams Fear of going insane
5
4 4 4 3
3
2 1 1 1 1
fore no further diagnostic studies (e.g., lumbar puncture, computed tomographic scanning) were performed. REFERENCES 1. Peck GL, DiGiovanna n. The retinoids. In: FitzpatrickTB, EisenAZ, WolffK, et al., eds.Dermatology ingeneralmedicine. 3rd ed. New York: McGraw-Hill, 1986;2582-608. 2. Hazen PG,CarneyJF, Walker AE,et al, Depression-a side effect of 13-cis-retinoic acid therapy. JAM ACAD DRRMATOl1983;9:278-9. 3. Meyskens FL, Jr. Short clinical reports. J AM ACAD DERMATOlI982;6:732-3.
1114
Journal of the American Academy of Dermatology
Brief communications
4. Physicians desk reference. 43rd ed. Oradell, NJ: Medical Economics, 1988:1713. 5. Diagnostic and statistical manual of mental disorders. 3rd ed.-revised. Washington, DC: American Psychiatric Association, 1987:218-24. 6. Ahlskog JE, O'Neill BP. Pseudotumor cerebri. Ann Intern Moo 1982;97:249-56. 7. Viraben R, Mathieu C, Fontan B. Benign intracranial hypertension during etretinate therapy for mycosis fungoides [Letter]. J AM ACAD DERMATOL 1985;13:515-7. 8. Ross DR, Coffey CE, Massey EW, et al. Depression and benign intracranial hypertension. Psychosomatics 1985; 26:387-93. 9. Restak RM. Pseudotumor cerebri, psychosis and hypervitaminosis A. J Nerv Mental Dis 1972;155:72-5.
Urticaria) vasculitis and Lyme disease Judyann C. Olson, MD, and Nancy B. Esterly, MD Milwaukee, Wisconsin Erythema chronicum migrans (ECM) is the classic skin lesionof Lyme disease, a multisystem diseasecaused by the spirochete Borrelia burgdorferi. I Other cutaneous manifestations of Lyme disease include localized and generalized urticaria, generalized macular eruptions,malar erythema in febrile patients.? and septal panniculitis.' We describe a child with urticarial vasculitis as the presenting feature of Lyme disease. Case report. A 4-year-old girl had sudden onset of erythematous, pruritic, indurated skin lesions that persisted for several days. Three weeks later the resolving skin lesions became increasingly ecchymotic. Results of a hemostasis screen were normal. Crops of new lesions then developed. The patient had diffuse arthralgias and angioedema of the lip and of the left side of the face. During the illness no fever, fatigue, or anorexia was associated. The patient's parents were uncertain whether she had been bitten by a tick; however, she had visited wooded areas in central Wisconsin. Review of systems was otherwise unremarkable. Results of a physical examination were normal except for the presence of multiple erythematous, slightly elevated, indurated, plaquelike, urticarial lesions that did not blanch completely on diascopy. Many lesions were surrounded by a pale, I to 2 mm halo. The lesions were present on the face, ears, trunk, extremities, buttocks, and sales. Large ecchymoses were present at the sites of old lesions on the dorsum of the feet and on the lower extremities. No petechiae were seen. There was no evidence of synovitis. Laboratory evaluation revealed the following results: white blood cells, 8.8 X 1031JlI, with 47% segmented neutrophils, 17% bands, 30% lymphocytes, 4% monocytes, 1% eosinophils, and 1% reactive lymphocytes; hemoglobin, 11.2 gm/dl; platelets, From the Department of Pediatrics, Divisions of Rheumatology and Dermatology, The Medical College of Wisconsin. Reprint requests: Judyann C. Olson, MD, Department of Pediatrics, The Medical College of Wisconsin, MACC Fund Research Center, 8701 Watertown Plank Rd" Milwaukee, WI 53226.
16/4/16618
490,OOO/~I; erythrocyte
sedimentation rate, 45 mrn/hr; albumin, 3.8 gm/dl: blood urea nitrogen, 10 mg/dl; creatinine, 0.4 mg/dl; SGOT (AST), 27 IU/L; SGPT (ALT), II IU/L; lactate dehydrogenase, 233 lULL, total protein, 7.2 gm/dl; negative cryoglobulins; IgE, 18 Vjml (normal 37 to 70 Vlml); 19G, 1326 mg/dl (normal 434 to 1164 mg/dl): IgA, 133 mg/dl (normal 22 to 137 mg/dl); IgM, 90 mg/dl (normal 41 to 188 mg/dl); antinuclear antibodies, negative; rapid plasma reagin, negative; C3, 229 mg/dl (normal 86 to 166 mg/dl), C4, 19.8 mg/dl (normal 13 to 32 mg/dl); CH50, 149 V/ml (normal 80 to 220 V / ml); hepatitis panel, negative; Epstein-Barr virus and cytomegalovirus titers, negative; polyvalent immunofluorescence antibody titer for B. burgdorferi, 1:256. A skin biopsyspecimen of a fresh lesionshowed a lymphocytic infiltrate surrounding superficial and deep dermal vessels, some degeneration of the vessel walls, and invasion by lymphocytes and eosinophils(Fig. 1). No thrombi, fibrin deposition, erythrocyte extravasation, or nuclear debris was noted. Direct immunofluorescence studies failed to demonstrate deposition of IgG, IgM, 19A, C3, or fibrin in either vesselwalls or at the dermoepidermal junction. In light of the elevated titer for Lyme disease, treatment with phenoxymethyl penicillin, 50 mg/kg/day for 2 weeks, was initiated. Symptoms improved dramatically but did not resolve entirely; therefore treatment was extended for 1 month. At the end of treatment the arthralgias and all skin lesionshad resolved. Telephone follow-up 7 months after treatment revealed neither recurrence of joint pain or skin lesions nor development of neurologic or arthritic symptoms.
DISCUSSION
Erythema chronicum migransisthe hallmark of Lyme disease.' However, Berger noted that a small number of patients (3/51) had secondarycutaneous manifestations. These includedlocalizedand generalizedurticaria, malar erythema, and generalized macular eruptions.' One patient had ECM, and subcutaneous nodules subsequently developed. The biopsyspecimen showed septal panniculitis without evidence of vasculitis. 3 ECM is not always present. In a study of childhood Lyme arthritis, more than half the patients had no history of rash, tick bite, or prodromal illness. In the absence of rash the diagnosis can be made on the basisof a compatibleexposure history,a compatibleclinicalsyndrome,and immunofluorescence antibodytiters of at least 1:256,the recognized value for a "positive" titer suggestive of B. burgdorferi exposure in an endemic area." Antibody testing for the Lyme spirocheteis specific, with false-positive results chiefly limited to other spirochetal illnesses- or, rarely, as a result of infectious mononucleosis or autoimmune disease." In our patient the history was not suggestive ofanother illness and resultsofserologicstudies were negative for syphilis. The resolution of the illness with penicillin therapy, seropositivity suggestive of exposure, and residence in an endemicarea supported the diagnosis of Lyme disease. Although urticaria has been documented in patients with Lyme disease.' we are unaware of previous reports
Acute depression from isotretinoin Pamela L. Scheinman, MD, * Gary L. Peck, MD, David R. Rubinow, MD, John J. DiGiovanna, MD, Donita L. Abangan, MD, and Paula D. Ravin, MD
Bethesda, Maryland A spectrum ofcentral nervoussystem sideeffects, similar to that observed with the hypervitaminosis A syndrome induced by retinyl esters has been described with other natural and synthetic retinoids.' For example, depressive symptoms, such as crying spells, malaise, and forgetfulness, have been noted in some patients receiving isotretinoin.e The depression subsides with discontinFrom the Dermatology Branch, National Cancer Institute, National Institutes ofHealth. Reprint requests: Gary L. Peck, MD, Dermatology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Room 12N238, Bethesda, MD 20892. "'Now at the Department of Dermatology, University of Rochester School ofMedicine, Rochester, N.Y. 16/4/20231
Journal of the American Academy of Dermatology
uatiorr' and recurs with reinstitution of therapy." In this article we describe seven patients in whom severe depression developed during isotretinoin therapy.
Material and methods. Seven patients, five women and two men, reported major depressive symptoms during treatment with oral isotretinoin. They participated in clinical trials of isotretinoin involving approximately 700 patients with cystic acne, psoriasis, cutaneous disorders of keratinization, or basal cell carcinoma. Patients involved in clinical trials were volunteersfrom whom informed consent was obtained. The diagnosis of depression wasmadeon the basisof the patients' spontaneous report of the recent onset of the cardinal symptoms of depression.i The diagnosis of a major depressive disorder was confirmed bya psychiatrist (D. R. R.) in the three patients who were interviewed during their depression. The rapid resolution of depression afterdiscontinuation of isotretinoin precluded a psychiatric interview while the remaining four patients were symptomatic.
Results. In five of the seven patients in whom depressivesymptoms developed during treatment with isotretinoin, the symptoms developed during the first course of therapy. The other two previously had one or two courses of treatment with isotretinoin without depression (Table I). The patients in this study voluntarily reported symptoms characteristic of a major depressive episode' during treatment with isotretinoin (Table II). The severity of these symptoms interfered with normal functioning in most patients. In each patient isotretinoin therapy was discontinued when depressive symptoms were reported. All symptoms resolvedwithin 2 to 7 days after discontinuation of the drug. Although two patients had a history of mild depression, none required medication or hospitalization. The depressiveepisodes during isotretinointherapy in patients 1 and 6 were much more severe than those previously experienced. During treatment in these two patients, fatigue, inability to concentrate, lack of motivation, forgetfulness, and crying spells also developed. In one patient (No.5) the relationship of depression to isotretinointherapy was confirmedby rechallenge, In this patient symptoms developed during the tenth week of the initial course of isotretinoin (0.7 mg/kg/day). The depression resolved within 7 days after discontinuation of the medication. Ten weeks later treatment was resumed at 10 mg/day and after a month increased to 20 rug/day (0.3 mg/kg/day). The depression reappeared during the third month of this second course of therapy. Discontinuation of isotretinoin was again followed by rapid disappearance of depressive symptoms. Three of seven patients also had headache during their depression. In one patient the headaches occurred daily and were not relieved by medication (acetaminophen). Headaches in all patients resolvedafter cessation of ther!ipy.One patient had dizzinessthat also resolved promptly.
Volume 22 Number 6, Part 1 June 1990
Briefcommunications 1113
Table I. Characteristics of therapeutic courses of isotretinoin associated with depression Age (yr)/
Time to onset"
Diagnosis
Sex
(wk)
mg/day
Acne Acne Acne Psoriasis Acne
31/M 22/F 24/F 26/F
8 10 14 47
80 40 40 60
10 8-12
40 17 40 40
Patient
No.
1 2 3 4 5
BCC Acne Mean
I
No.of
47/F
7
261M
6 14
32
Time to
c\eart
prior mg/kg/day
courses
Headache
1.3
2:\:
0.1 0.1 1.1
0 0
+
1§
+ +
42jF
1st course 2nd course 6 7
Mean dosage
(days)
7 7 2 4
0.1
0
OJ
1
0.5 0.5 0.1
0
2
0
7
7 2
+, Present; -, absent; Bee.
basal cellcarcinoma. ·Time to' presentation of depression after initiationof therapy. t After discontinuation of therapy. :j:Mean dosage for first coursewas 0.3 rng/kg/day for 16 weeks; meandosageforsecond coursewas2 mg/kg/day for 26 weeks; interval between second and third course was 3.5 years. §Mean dosage for first course was 2,4 mg/kg/day; interval between first and second course was 5 years.
Funduscopic examination in four patients during the depressive episode failed to identify papilledema. At the time ofpresentation none of the patients were taking other medications that have been implicated in the development of pseudotumor cerebri. 6 Discussion. The results of this study suggest that depression is a rare side effect of isotretinoin that was spontaneously reported in 1 of approximately 100 patients. In these patients the onset of depression was related to neither dosage nor time. Irrespective of dosage, all depressive symptoms rapidly resolved within 1 week of cessation of medication. On the basis of the patients' psychiatric history, the development of a major depressive episode in all seven patients in this study most likely represents an idiosyncratic side effect of isotretinoin rather than a predictable effect in a subset of patients predisposed to develop major depressions. Treatment with retinoids can produce benign intracranial hypertension (BIH).l,7 BIH also has been reported after the resolution of a major depressive syndrome.f Nonetheless, depression was reported to precede by 1 year the diagnosis of pseudotumor cerebri in one patient with chronic hypervitaminosis A.9 BIH is characterized by (1) increased intracranial pressure, (2) normal cerebrospinal fluid composition, (3) normal radiographic studies, and (4) symptoms and signs that result from the increased intracranial pressure, such as headache, visual disturbances, and papilledema.f Thus the symptoms of headache and depression observed in this study could suggest a diagnosis of BIll. However, the rapid resolution of the depression after discontinuation of isotretinoin in all patients and the negative funduscopic examination in four patients argue against a diagnosis of BIR. There-
Table II. Symptoms observed during isotretinoin treatment in seven patients developing a major depression No. of patienls with symptom
Fatigue (increased sleep, loss of energy) Irritability Decreased concentration Sadness Crying spells Loss of motivation (school, social contacts) Forgetfulness Suicidal ideation Anhedonia Abnormal dreams Fear of going insane
5
4 4 4 3
3
2 1 1 1 1
fore no further diagnostic studies (e.g., lumbar puncture, computed tomographic scanning) were performed. REFERENCES 1. Peck GL, DiGiovanna n. The retinoids. In: FitzpatrickTB, EisenAZ, WolffK, et al., eds.Dermatology ingeneralmedicine. 3rd ed. New York: McGraw-Hill, 1986;2582-608. 2. Hazen PG,CarneyJF, Walker AE,et al, Depression-a side effect of 13-cis-retinoic acid therapy. JAM ACAD DRRMATOl1983;9:278-9. 3. Meyskens FL, Jr. Short clinical reports. J AM ACAD DERMATOlI982;6:732-3.
1114
Journal of the American Academy of Dermatology
Brief communications
4. Physicians desk reference. 43rd ed. Oradell, NJ: Medical Economics, 1988:1713. 5. Diagnostic and statistical manual of mental disorders. 3rd ed.-revised. Washington, DC: American Psychiatric Association, 1987:218-24. 6. Ahlskog JE, O'Neill BP. Pseudotumor cerebri. Ann Intern Moo 1982;97:249-56. 7. Viraben R, Mathieu C, Fontan B. Benign intracranial hypertension during etretinate therapy for mycosis fungoides [Letter]. J AM ACAD DERMATOL 1985;13:515-7. 8. Ross DR, Coffey CE, Massey EW, et al. Depression and benign intracranial hypertension. Psychosomatics 1985; 26:387-93. 9. Restak RM. Pseudotumor cerebri, psychosis and hypervitaminosis A. J Nerv Mental Dis 1972;155:72-5.
Urticaria) vasculitis and Lyme disease Judyann C. Olson, MD, and Nancy B. Esterly, MD Milwaukee, Wisconsin Erythema chronicum migrans (ECM) is the classic skin lesionof Lyme disease, a multisystem diseasecaused by the spirochete Borrelia burgdorferi. I Other cutaneous manifestations of Lyme disease include localized and generalized urticaria, generalized macular eruptions,malar erythema in febrile patients.? and septal panniculitis.' We describe a child with urticarial vasculitis as the presenting feature of Lyme disease. Case report. A 4-year-old girl had sudden onset of erythematous, pruritic, indurated skin lesions that persisted for several days. Three weeks later the resolving skin lesions became increasingly ecchymotic. Results of a hemostasis screen were normal. Crops of new lesions then developed. The patient had diffuse arthralgias and angioedema of the lip and of the left side of the face. During the illness no fever, fatigue, or anorexia was associated. The patient's parents were uncertain whether she had been bitten by a tick; however, she had visited wooded areas in central Wisconsin. Review of systems was otherwise unremarkable. Results of a physical examination were normal except for the presence of multiple erythematous, slightly elevated, indurated, plaquelike, urticarial lesions that did not blanch completely on diascopy. Many lesions were surrounded by a pale, I to 2 mm halo. The lesions were present on the face, ears, trunk, extremities, buttocks, and sales. Large ecchymoses were present at the sites of old lesions on the dorsum of the feet and on the lower extremities. No petechiae were seen. There was no evidence of synovitis. Laboratory evaluation revealed the following results: white blood cells, 8.8 X 1031JlI, with 47% segmented neutrophils, 17% bands, 30% lymphocytes, 4% monocytes, 1% eosinophils, and 1% reactive lymphocytes; hemoglobin, 11.2 gm/dl; platelets, From the Department of Pediatrics, Divisions of Rheumatology and Dermatology, The Medical College of Wisconsin. Reprint requests: Judyann C. Olson, MD, Department of Pediatrics, The Medical College of Wisconsin, MACC Fund Research Center, 8701 Watertown Plank Rd" Milwaukee, WI 53226.
16/4/16618
490,OOO/~I; erythrocyte
sedimentation rate, 45 mrn/hr; albumin, 3.8 gm/dl: blood urea nitrogen, 10 mg/dl; creatinine, 0.4 mg/dl; SGOT (AST), 27 IU/L; SGPT (ALT), II IU/L; lactate dehydrogenase, 233 lULL, total protein, 7.2 gm/dl; negative cryoglobulins; IgE, 18 Vjml (normal 37 to 70 Vlml); 19G, 1326 mg/dl (normal 434 to 1164 mg/dl): IgA, 133 mg/dl (normal 22 to 137 mg/dl); IgM, 90 mg/dl (normal 41 to 188 mg/dl); antinuclear antibodies, negative; rapid plasma reagin, negative; C3, 229 mg/dl (normal 86 to 166 mg/dl), C4, 19.8 mg/dl (normal 13 to 32 mg/dl); CH50, 149 V/ml (normal 80 to 220 V / ml); hepatitis panel, negative; Epstein-Barr virus and cytomegalovirus titers, negative; polyvalent immunofluorescence antibody titer for B. burgdorferi, 1:256. A skin biopsyspecimen of a fresh lesionshowed a lymphocytic infiltrate surrounding superficial and deep dermal vessels, some degeneration of the vessel walls, and invasion by lymphocytes and eosinophils(Fig. 1). No thrombi, fibrin deposition, erythrocyte extravasation, or nuclear debris was noted. Direct immunofluorescence studies failed to demonstrate deposition of IgG, IgM, 19A, C3, or fibrin in either vesselwalls or at the dermoepidermal junction. In light of the elevated titer for Lyme disease, treatment with phenoxymethyl penicillin, 50 mg/kg/day for 2 weeks, was initiated. Symptoms improved dramatically but did not resolve entirely; therefore treatment was extended for 1 month. At the end of treatment the arthralgias and all skin lesionshad resolved. Telephone follow-up 7 months after treatment revealed neither recurrence of joint pain or skin lesions nor development of neurologic or arthritic symptoms.
DISCUSSION
Erythema chronicum migransisthe hallmark of Lyme disease.' However, Berger noted that a small number of patients (3/51) had secondarycutaneous manifestations. These includedlocalizedand generalizedurticaria, malar erythema, and generalized macular eruptions.' One patient had ECM, and subcutaneous nodules subsequently developed. The biopsyspecimen showed septal panniculitis without evidence of vasculitis. 3 ECM is not always present. In a study of childhood Lyme arthritis, more than half the patients had no history of rash, tick bite, or prodromal illness. In the absence of rash the diagnosis can be made on the basisof a compatibleexposure history,a compatibleclinicalsyndrome,and immunofluorescence antibodytiters of at least 1:256,the recognized value for a "positive" titer suggestive of B. burgdorferi exposure in an endemic area." Antibody testing for the Lyme spirocheteis specific, with false-positive results chiefly limited to other spirochetal illnesses- or, rarely, as a result of infectious mononucleosis or autoimmune disease." In our patient the history was not suggestive ofanother illness and resultsofserologicstudies were negative for syphilis. The resolution of the illness with penicillin therapy, seropositivity suggestive of exposure, and residence in an endemicarea supported the diagnosis of Lyme disease. Although urticaria has been documented in patients with Lyme disease.' we are unaware of previous reports
