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Oral cyclosporine for severe chronic idiopathic urticaria and angioedema
Oral cyclosporine for severe chronic idiopathic urticaria and angioedema Mark S. Fradin, MD, Charles N. Ellis, MD, Michael T. Goldfarb, MD, and John J. Voorhees, MD Ann Arbor, Michigan Three patients with chronic urticaria, two of whom also had angioedema, were treated with oral cyclosporine, 6 mg/kg per day. In each patient, complete resolution of symptoms occurred within the first week of therapy; however,all patients eventually had to stop therapy as a result of side effects. On stopping therapy, all side effects resolved and the urticaria and angioedema recurred. Although cyclosporine therapy is not an appropriate treatment of urticaria, the results of this preliminary study suggest that cyclosporine and related drugs should be investigated in the treatment of mast cell-mediated diseases. (J AM ACAD DERMATOL 1991;25:1065-7.)
During our investigations into the role of cyclosporine in the treatment of cutaneous conditions, we have been evaluating its spectrum of activity. 1 Subsequent to our previous report, l we chanced upon three patients with severe, chronic urticaria in whom cyclosporine could be tested. These three patients were unresponsive to conventional therapies. We were surprised by the dramatic response to treatment with cyclosporine.
PATIENTS AND METHODS Three patients with chronic idiopathic urticaria (two of whom also had angioedema) were enrolled in this openlabel study. All patients had failed to respond to HI antihistamines alone or in combination with H2 antihistamines. Our protocol was approved by the Food and Drug Administration as a physician-sponsored investigation and by the University of Michigan Medical Center institutional review board. All patients gave informed consent after receiving a full explanation of the protocol. Each patient received oral cyclosporine solution (Sandimmune) at a dosage regimen of 6 mg/kg per day.
From the Dermatopharmacology Unit of the Department of Dermatology, University of Michigan Medical Center. Supported in part by the Babcock Dermatologic Endowment, Ann Arbor, Michigan, and the Clinical and Philanthropic Funds of the Department of Dermatology. Drs. Ellis and Voorhees serve as consultants to Sandoz Pharmaceuticals Corp. Reprint requests: Charles N. Ellis, MD, Department of Dermatology, University of Michigan Medical Center, 1910 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0314. 16/1/32350
CASE REPORTS Case 1. A 42-year-old woman had a 3D-year history of hives and a 5-year history of angioedema, which at times had been severe enough to require hospitalization. Despite a dosage regimen of hydroxyzine hydrochloride up to 300 mg per day, she continued to have hives daily, together with intermittent attacks of angioedema. Because of our concern about triggering an attack of angioedema by sudden discontinuation of the oral antihistamine, she continued to take this when cyc1osporine was initiated. Within 3 days, she noted complete disappearance of her hives for the first time since childhood. After 1 week of cyclosporine therapy, despite a reduction in hydroxyzine hydrochloride to 50 mg per day, she reported no longer feeling the sensation of swelling in her throat and mouth that had previously affected her at least twice weekly. By the third week of cyc1osporine therapy, she was able to stop all oral antihistamines and had complete absence of both hives and episodes of angioedema. Case 2. A 43-year-old woman had urticaria and angioedema for 2 years. The urticaria often affected more than 90% of her body, and the angioedema caused difficulty in breathing and swallowing, requiring numerous visits to an emergency room. Although her condition was controlled reasonably well by prednisone, 30 to 60 mgper day, she had become cushingoid and had to stop corticosteroid therapy. Within 48 hours of initiating cyclosporine, she noted the complete resolution of her symptoms for the first time in 2 years. Case 3. A 56-year-old woman had 10% of her body surface area involved with hives when she started a regimen of cyclosporine therapy. Within 1 week, she noted complete absence of hives for the first time in 5 years. Side effects. As a result of side effects, all patients eventually required discontinuation of cyclosporine after
1065
1066
Journal of the American Academy of Dermatology
Fradin et al.
3 to 9 weeks of treatment. Patients 1 and 2 had a history of migraine headaches and experienced the onset ofsevere headaches that were refractory to treatment within 1 week of starting cyclosporine therapy. Patients 1 and 2 also had a: rise in serum creatinine level up to 70% more than before therapy. Patients 1 and 3 experienced an increase in blood pressure to hypertensive levels. Other side effects included nausea, fatigue, paresthesia, and increased cold sensitivity of the hands and feet. All side effects were typical of cyclosporine therapy,2 although the headaches were unusually severe. Reduction of the cyc1osporine to 3 mg/kg per day was ineffective in preventing the side effects, and all patients noted return of their hives on this dosage. All side effects and laboratory abnormalities resolved after discontinuation of cyc1osporine. FoUow~up. After stopping cyc1osporine, patients 2 and 3 noted return of their symptoms within 48 hours. Patient 1 reported that her angioedema and hives returned within a few days, but her hives, even 6 months after stopping cyclosporine, were never as prevalent as before taking the
drug.
DISCUSSION
The mechanism by which cyclosporine works in the treatment of urticaria and angioedema remains unknown. Cyclosporine has been shown to inhibit the release of mast cell-derived mediators in vitro, however. z-5 Activation of mast cells normally leads to the release of histamine as well as a variety of proinflammatory mediators, including leukotrienes, prostaglandin D z, and platelet-activating factor. 6 Because such mediators are important in the pathogenesis of urticaria and angioedema,7-9 inhibition of their release may explain the beneficial effect we observed in our patients. Studies of human lung mast cells in vitro show that cyclosporine, at concentrations comparable to those achieved with in vivo use, can irreversibly inhibit the release of histamine and prostaglandin Dz. 5, 10 In vitro, cyclosporine also inhibits histamine release from human basophils and rat mast cells, as well as synthesis of leukotriene C4 in human basophils and lung mast cells. z-4, 10-12 An increase in intracellular calcium is necessary for histamine and 1eukotriene secretion from mast cells 13- IS ; cyclosporine appears to interfere with the calcium-dependent release of these mediators. 4, 16 Despite its direct effects on mast cells, the mechanism of action of cycIosporine may be related in part to its effects on T cells. In chronic urticaria, approximately half the cellular infiltrate is composed of
T 1ymphocytes. 17 Cyclosporine inhibits the release of cytokines from T cells,18 and the interaction of T cells with mast cells may be required for the development ofthe lesions of chronic urticaria. 17, 19 Thus cyclosporine may prevent urticaria and angioedema by inhibiting T cell-stimulated release of mast cell mediators. Cyclosporine was ineffective in one case of mastocytosis, however.20 To our knowledge this is the first demonstration of the dramatic efficacy of cycIosporine in the treatment of chronic urticaria and angioedema. However, the potential side effects of cyclosporine, particularly decreased renal function, would preclude its long-term use in the treatment of common hives. Only in our two patients with potentially life-threatening angioedema might a longer use of cyclosporine have been considered. Both patients with angioedema had exacerbation of migraine headaches during cyclosporine therapy that necessitated early discontinuation, however. We did not use agents that inhibit the metabolism of cyc1osporineZI that might have allowed a reduction in cyclosporine dosage; such an approach eliminated cycIosporine-induced headaches in one reported patient. 22 The cyclosporine used in this study was a gift from Sandoz Research Institute, East Hanover, N.J. REFERENCES 1. Gupta AK, Ellis CN, Nickoloff BJ, et al. Oral cyclosporine in the treatment of inflammatory and noninflammatory dermatoses. Arch Dermatol 1990;126:339-50. 2. Pedersen C, Pennin H, Stahl Skov P, et al. Inhibitory effect of cyclosporin A on histamine release from human leukocytes and rat mast cells. Allergy 1985;40:103-7. 3. Hultsch T, Rodriguez JL, Kaliner MA, et al. Cyclosporin A inhibits degranulation of rat basophilic leukemia cells and human basophils. Inhibition of mediator release without affecting PI hydrolysis or Ca2+ fluxes. J Immunol 1990;144:2659-64. 4. Draberova L. Cyclosporin A inhibits rat mast cell activation. Eur J ImmunoI1990;20:1469-73. 5. Triggiani M, Cirillo R, Lichtenstein LM, et al. Inhibition ofhistamine and prostaglandin D 2 release from human lung mast cells by ciclosporin A. Int Arch Allergy Appl Immunol 1989;88:253-5. 6. Schwartz LB, Austen KF. Structure and function of the chemical mediators ofmast cells. ProgAllergy 1984;34:271321. 7. Green GR, Koelsche GA, Kierland RR. Etiology and pathogenesis of chronic urticaria. Ann Allergy 1965; 23:30-6. 8. KaplanAP. Urticaria and angioedema. In: Middleton E Jr, Reed CE, Ellis EF, eds. Allergy: principles and practice. St Louis: Mosby-Year Book, 1983:1341-60. 9. Monroe EW, Jones HE. Urticaria. Arch Dermatol 1977;113:80-90. 10. Ezeamuzie IC, Assem ES. Inhibition of histamine release
Volume 25 Number 6, Part 1 December 1991
11.
12. 13.
14.
15.
Cyclosporine for urticaria/angioedema 1067
from human lung and rat peritoneal mast cells by cyclesporin A. Agents Actions 1990;30:110-3. Cirillo R, Triggiani M, Siri L, et a1. Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin. 1 Immunol 1990; 144:3891-7. Marone G, Triggiani M, Cirillo R, et al. Cyclosporin A inhibits the release of histamine and peptide leukotriene C4 from human lung mast cells. Ric Clin Lab 1988;18:53-9. Kaliner M, Austen KF. A sequence of biochemical events in the antigen-induced release of chemical mediators from sensitized human lung tissue. 1 Exp Med 1973;138:107794. Diamont B, Grosman N, Stahl Skov P, et al. Effect of divalent cations and metabolic energy on the anaphylactic histamine release from rat peritoneal mast cells. Int Arch Allergy Appl Immunol1974;47:4l2-24. Tanizaki Y, Akagi K, Lee KN, et al. Inhibitory effect of nifedipine and cromolyn sodium on skin reactions and 45Ca uptake and histamine release in rat mast cells induced by various stimulating agents. Int Arch Allergy Appl Immunol1983;72:102-9.
16. Ezeamuzie CI, Assem ES. Anti-allergic properties of cyclosporin A: inhibition of mediator release from human basophils and rat basophilic leukemia cells (RBL-2H3). Immunopharmacol1990;20:31-43. 17. Elias 1, Boss E, Kaplan AP. Studies ofthe cellular infiltrate of chronic idiopathic urticaria: prominence of T-1ymphocytes, monocytes, and mast cells. 1 Allergy C!in Immuno! 1986;78:914-8. 18. Kahan BD. Cyclosporine. N Eng1 1 Med 1989;321:172538. 19. Kaplan AP. Urticaria: the relationship of duration oflesion to pathogenesis. Allergy Proc 1990;11:15-8. 20. Metcalf DD. The treatment of mastocytosis: an overview. 1 Invest Dermatol1991;96:55S-9S. 21. Fradin MS, Ellis CN, Voorhees 11. Management of patients and side effects during cyclosporine therapy for cutaneous disorders. JAM ACADDERMATOL 1990;23:126575. 22. Shelley WB, Shelley ED. Portrait of a practice. Cutis 1990;46:469-72.
ABSTRACTS Replication of Epstein-Barr virus and therapy of oral hairy leukoplakia with acyclovir
Anti-Borrelia burgdorferi antibodies in sclerodermiform cutaneous disorders
Naher H, Helfrich S, Hartmann M, et al. Hautarzt 1990;41:680-2 (German)
Garcia Patos V, Pujol RM, ColI P, et al. Actas Derme-Sif 1990;81:663-7 (Spanish)
The therapy of choice for oral hairy leukoplakia in patients infected with the human immunodeficiency virus (HIV) is acyclovir. During treatment the replication of Epstein-Barr virus (EBV) in cells scraped from the epithelium of hairy leukoplakia was investigated by in situ hybridization. On the second day of treatment a slight reduction and on the fifth day a marked reduction in the replication were observed. On the eighth day oftreatment replication ofEBV could hardly be detected. At that time a marked regression in the leukoplakia was seen. Within another 7 days the lesions had completely disappeared. These findings demonstrate the relation between treatment with acyclovir and inhibition of EBV replication in hairy leukoplakia and the relation between inhibition of EBV replication and remission of hairy leukoplakia. Yehudi M. Felman, MD
The presence of antibodies against Borrelia burgdorferi by indirect immunofluorescence assay was determined in the serum of the following groups: (a) 30 patients with morphea (linear, with a single or multiple patches); (b) 8 patients with lichen sclerosus et atrophicus (generalized or genital); (c) II patients with other cutaneous disorders by (pseudosc1eroderma, CREST syndrome, insect bites, lymphadenosis benigna cutis); and (d) 30 patients without any cutaneous diseases.
Receptors of epidermal growth factor (EGF) in basal cell carcinoma, squamous cell carcinoma, and malignant mela~ noma Hagedorn M, Vanscheidt W, Strasser W, et al. H&G Hautkr 1990;65:568·70 (German) The authors studied the binding ofepidermal growth factor receptors (EGF-R) in 19 basal cell carcinomas, eight squamous cell carcinomas, and nine malignant melanomas. Specific binding of EGF-R was detected in 10 basal cell carcinomas and in all eight squamous cell carcinomas. None of the malignant melanomas showed EGF·R binding. A comparative study of the receptor status versus clinical prognostic data, such as grading and clinical course, did not reveal any significant differences, whereas in ovarian carcinomas, the EGF-R correlates with prognosis. Yehudi M. Felman, MD
Indirect immunofluorescence assay showed reactive titers of I:64 in three patients with localized scleroderma, in one patient with cutaneous generalized lichen sclerosus et atrophicus, in one patient with CREST syndrome, and in one patient with lymphadenosis benigna cutis. All patients in the control group had negative antibody titers. Yehudi M. Felman, MD
Paroxysmal hematoma Stieler W, Heinze-Werlitz C. Hautarzt 1990;41:270-1 (German) Paroxysmal hematoma of the fingers (Achenbach's syndrome) is rarely reported. It often occurs spontaneously or after minor injuries. Because of the sudden onset of intense burning pain and the development of hematoma, the patients are frequently alarmed, The cause is still unknown. The authors report three cases ofparoxysmal hematoma of the fingers. The harmless nature of the condition is emphasized. Yehudi M. Felman. MD
During our investigations into the role of cyclosporine in the treatment of cutaneous conditions, we have been evaluating its spectrum of activity. 1 Subsequent to our previous report, l we chanced upon three patients with severe, chronic urticaria in whom cyclosporine could be tested. These three patients were unresponsive to conventional therapies. We were surprised by the dramatic response to treatment with cyclosporine.
PATIENTS AND METHODS Three patients with chronic idiopathic urticaria (two of whom also had angioedema) were enrolled in this openlabel study. All patients had failed to respond to HI antihistamines alone or in combination with H2 antihistamines. Our protocol was approved by the Food and Drug Administration as a physician-sponsored investigation and by the University of Michigan Medical Center institutional review board. All patients gave informed consent after receiving a full explanation of the protocol. Each patient received oral cyclosporine solution (Sandimmune) at a dosage regimen of 6 mg/kg per day.
From the Dermatopharmacology Unit of the Department of Dermatology, University of Michigan Medical Center. Supported in part by the Babcock Dermatologic Endowment, Ann Arbor, Michigan, and the Clinical and Philanthropic Funds of the Department of Dermatology. Drs. Ellis and Voorhees serve as consultants to Sandoz Pharmaceuticals Corp. Reprint requests: Charles N. Ellis, MD, Department of Dermatology, University of Michigan Medical Center, 1910 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0314. 16/1/32350
CASE REPORTS Case 1. A 42-year-old woman had a 3D-year history of hives and a 5-year history of angioedema, which at times had been severe enough to require hospitalization. Despite a dosage regimen of hydroxyzine hydrochloride up to 300 mg per day, she continued to have hives daily, together with intermittent attacks of angioedema. Because of our concern about triggering an attack of angioedema by sudden discontinuation of the oral antihistamine, she continued to take this when cyc1osporine was initiated. Within 3 days, she noted complete disappearance of her hives for the first time since childhood. After 1 week of cyclosporine therapy, despite a reduction in hydroxyzine hydrochloride to 50 mg per day, she reported no longer feeling the sensation of swelling in her throat and mouth that had previously affected her at least twice weekly. By the third week of cyc1osporine therapy, she was able to stop all oral antihistamines and had complete absence of both hives and episodes of angioedema. Case 2. A 43-year-old woman had urticaria and angioedema for 2 years. The urticaria often affected more than 90% of her body, and the angioedema caused difficulty in breathing and swallowing, requiring numerous visits to an emergency room. Although her condition was controlled reasonably well by prednisone, 30 to 60 mgper day, she had become cushingoid and had to stop corticosteroid therapy. Within 48 hours of initiating cyclosporine, she noted the complete resolution of her symptoms for the first time in 2 years. Case 3. A 56-year-old woman had 10% of her body surface area involved with hives when she started a regimen of cyclosporine therapy. Within 1 week, she noted complete absence of hives for the first time in 5 years. Side effects. As a result of side effects, all patients eventually required discontinuation of cyclosporine after
1065
1066
Journal of the American Academy of Dermatology
Fradin et al.
3 to 9 weeks of treatment. Patients 1 and 2 had a history of migraine headaches and experienced the onset ofsevere headaches that were refractory to treatment within 1 week of starting cyclosporine therapy. Patients 1 and 2 also had a: rise in serum creatinine level up to 70% more than before therapy. Patients 1 and 3 experienced an increase in blood pressure to hypertensive levels. Other side effects included nausea, fatigue, paresthesia, and increased cold sensitivity of the hands and feet. All side effects were typical of cyclosporine therapy,2 although the headaches were unusually severe. Reduction of the cyc1osporine to 3 mg/kg per day was ineffective in preventing the side effects, and all patients noted return of their hives on this dosage. All side effects and laboratory abnormalities resolved after discontinuation of cyc1osporine. FoUow~up. After stopping cyc1osporine, patients 2 and 3 noted return of their symptoms within 48 hours. Patient 1 reported that her angioedema and hives returned within a few days, but her hives, even 6 months after stopping cyclosporine, were never as prevalent as before taking the
drug.
DISCUSSION
The mechanism by which cyclosporine works in the treatment of urticaria and angioedema remains unknown. Cyclosporine has been shown to inhibit the release of mast cell-derived mediators in vitro, however. z-5 Activation of mast cells normally leads to the release of histamine as well as a variety of proinflammatory mediators, including leukotrienes, prostaglandin D z, and platelet-activating factor. 6 Because such mediators are important in the pathogenesis of urticaria and angioedema,7-9 inhibition of their release may explain the beneficial effect we observed in our patients. Studies of human lung mast cells in vitro show that cyclosporine, at concentrations comparable to those achieved with in vivo use, can irreversibly inhibit the release of histamine and prostaglandin Dz. 5, 10 In vitro, cyclosporine also inhibits histamine release from human basophils and rat mast cells, as well as synthesis of leukotriene C4 in human basophils and lung mast cells. z-4, 10-12 An increase in intracellular calcium is necessary for histamine and 1eukotriene secretion from mast cells 13- IS ; cyclosporine appears to interfere with the calcium-dependent release of these mediators. 4, 16 Despite its direct effects on mast cells, the mechanism of action of cycIosporine may be related in part to its effects on T cells. In chronic urticaria, approximately half the cellular infiltrate is composed of
T 1ymphocytes. 17 Cyclosporine inhibits the release of cytokines from T cells,18 and the interaction of T cells with mast cells may be required for the development ofthe lesions of chronic urticaria. 17, 19 Thus cyclosporine may prevent urticaria and angioedema by inhibiting T cell-stimulated release of mast cell mediators. Cyclosporine was ineffective in one case of mastocytosis, however.20 To our knowledge this is the first demonstration of the dramatic efficacy of cycIosporine in the treatment of chronic urticaria and angioedema. However, the potential side effects of cyclosporine, particularly decreased renal function, would preclude its long-term use in the treatment of common hives. Only in our two patients with potentially life-threatening angioedema might a longer use of cyclosporine have been considered. Both patients with angioedema had exacerbation of migraine headaches during cyclosporine therapy that necessitated early discontinuation, however. We did not use agents that inhibit the metabolism of cyc1osporineZI that might have allowed a reduction in cyclosporine dosage; such an approach eliminated cycIosporine-induced headaches in one reported patient. 22 The cyclosporine used in this study was a gift from Sandoz Research Institute, East Hanover, N.J. REFERENCES 1. Gupta AK, Ellis CN, Nickoloff BJ, et al. Oral cyclosporine in the treatment of inflammatory and noninflammatory dermatoses. Arch Dermatol 1990;126:339-50. 2. Pedersen C, Pennin H, Stahl Skov P, et al. Inhibitory effect of cyclosporin A on histamine release from human leukocytes and rat mast cells. Allergy 1985;40:103-7. 3. Hultsch T, Rodriguez JL, Kaliner MA, et al. Cyclosporin A inhibits degranulation of rat basophilic leukemia cells and human basophils. Inhibition of mediator release without affecting PI hydrolysis or Ca2+ fluxes. J Immunol 1990;144:2659-64. 4. Draberova L. Cyclosporin A inhibits rat mast cell activation. Eur J ImmunoI1990;20:1469-73. 5. Triggiani M, Cirillo R, Lichtenstein LM, et al. Inhibition ofhistamine and prostaglandin D 2 release from human lung mast cells by ciclosporin A. Int Arch Allergy Appl Immunol 1989;88:253-5. 6. Schwartz LB, Austen KF. Structure and function of the chemical mediators ofmast cells. ProgAllergy 1984;34:271321. 7. Green GR, Koelsche GA, Kierland RR. Etiology and pathogenesis of chronic urticaria. Ann Allergy 1965; 23:30-6. 8. KaplanAP. Urticaria and angioedema. In: Middleton E Jr, Reed CE, Ellis EF, eds. Allergy: principles and practice. St Louis: Mosby-Year Book, 1983:1341-60. 9. Monroe EW, Jones HE. Urticaria. Arch Dermatol 1977;113:80-90. 10. Ezeamuzie IC, Assem ES. Inhibition of histamine release
Volume 25 Number 6, Part 1 December 1991
11.
12. 13.
14.
15.
Cyclosporine for urticaria/angioedema 1067
from human lung and rat peritoneal mast cells by cyclesporin A. Agents Actions 1990;30:110-3. Cirillo R, Triggiani M, Siri L, et a1. Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin. 1 Immunol 1990; 144:3891-7. Marone G, Triggiani M, Cirillo R, et al. Cyclosporin A inhibits the release of histamine and peptide leukotriene C4 from human lung mast cells. Ric Clin Lab 1988;18:53-9. Kaliner M, Austen KF. A sequence of biochemical events in the antigen-induced release of chemical mediators from sensitized human lung tissue. 1 Exp Med 1973;138:107794. Diamont B, Grosman N, Stahl Skov P, et al. Effect of divalent cations and metabolic energy on the anaphylactic histamine release from rat peritoneal mast cells. Int Arch Allergy Appl Immunol1974;47:4l2-24. Tanizaki Y, Akagi K, Lee KN, et al. Inhibitory effect of nifedipine and cromolyn sodium on skin reactions and 45Ca uptake and histamine release in rat mast cells induced by various stimulating agents. Int Arch Allergy Appl Immunol1983;72:102-9.
16. Ezeamuzie CI, Assem ES. Anti-allergic properties of cyclosporin A: inhibition of mediator release from human basophils and rat basophilic leukemia cells (RBL-2H3). Immunopharmacol1990;20:31-43. 17. Elias 1, Boss E, Kaplan AP. Studies ofthe cellular infiltrate of chronic idiopathic urticaria: prominence of T-1ymphocytes, monocytes, and mast cells. 1 Allergy C!in Immuno! 1986;78:914-8. 18. Kahan BD. Cyclosporine. N Eng1 1 Med 1989;321:172538. 19. Kaplan AP. Urticaria: the relationship of duration oflesion to pathogenesis. Allergy Proc 1990;11:15-8. 20. Metcalf DD. The treatment of mastocytosis: an overview. 1 Invest Dermatol1991;96:55S-9S. 21. Fradin MS, Ellis CN, Voorhees 11. Management of patients and side effects during cyclosporine therapy for cutaneous disorders. JAM ACADDERMATOL 1990;23:126575. 22. Shelley WB, Shelley ED. Portrait of a practice. Cutis 1990;46:469-72.
ABSTRACTS Replication of Epstein-Barr virus and therapy of oral hairy leukoplakia with acyclovir
Anti-Borrelia burgdorferi antibodies in sclerodermiform cutaneous disorders
Naher H, Helfrich S, Hartmann M, et al. Hautarzt 1990;41:680-2 (German)
Garcia Patos V, Pujol RM, ColI P, et al. Actas Derme-Sif 1990;81:663-7 (Spanish)
The therapy of choice for oral hairy leukoplakia in patients infected with the human immunodeficiency virus (HIV) is acyclovir. During treatment the replication of Epstein-Barr virus (EBV) in cells scraped from the epithelium of hairy leukoplakia was investigated by in situ hybridization. On the second day of treatment a slight reduction and on the fifth day a marked reduction in the replication were observed. On the eighth day oftreatment replication ofEBV could hardly be detected. At that time a marked regression in the leukoplakia was seen. Within another 7 days the lesions had completely disappeared. These findings demonstrate the relation between treatment with acyclovir and inhibition of EBV replication in hairy leukoplakia and the relation between inhibition of EBV replication and remission of hairy leukoplakia. Yehudi M. Felman, MD
The presence of antibodies against Borrelia burgdorferi by indirect immunofluorescence assay was determined in the serum of the following groups: (a) 30 patients with morphea (linear, with a single or multiple patches); (b) 8 patients with lichen sclerosus et atrophicus (generalized or genital); (c) II patients with other cutaneous disorders by (pseudosc1eroderma, CREST syndrome, insect bites, lymphadenosis benigna cutis); and (d) 30 patients without any cutaneous diseases.
Receptors of epidermal growth factor (EGF) in basal cell carcinoma, squamous cell carcinoma, and malignant mela~ noma Hagedorn M, Vanscheidt W, Strasser W, et al. H&G Hautkr 1990;65:568·70 (German) The authors studied the binding ofepidermal growth factor receptors (EGF-R) in 19 basal cell carcinomas, eight squamous cell carcinomas, and nine malignant melanomas. Specific binding of EGF-R was detected in 10 basal cell carcinomas and in all eight squamous cell carcinomas. None of the malignant melanomas showed EGF·R binding. A comparative study of the receptor status versus clinical prognostic data, such as grading and clinical course, did not reveal any significant differences, whereas in ovarian carcinomas, the EGF-R correlates with prognosis. Yehudi M. Felman, MD
Indirect immunofluorescence assay showed reactive titers of I:64 in three patients with localized scleroderma, in one patient with cutaneous generalized lichen sclerosus et atrophicus, in one patient with CREST syndrome, and in one patient with lymphadenosis benigna cutis. All patients in the control group had negative antibody titers. Yehudi M. Felman, MD
Paroxysmal hematoma Stieler W, Heinze-Werlitz C. Hautarzt 1990;41:270-1 (German) Paroxysmal hematoma of the fingers (Achenbach's syndrome) is rarely reported. It often occurs spontaneously or after minor injuries. Because of the sudden onset of intense burning pain and the development of hematoma, the patients are frequently alarmed, The cause is still unknown. The authors report three cases ofparoxysmal hematoma of the fingers. The harmless nature of the condition is emphasized. Yehudi M. Felman. MD