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Mycosis fungoides—like lesions associated with phenytoin and carbamazepine therapy
Mycosis fungoides-like lesions associated with phenytoin and carbamazepine therapy Udo Rijlaarsdam, MD,a Erik Scheffer, MD,b Chris J. L. M. Meijer, MD,b Metske R. J. Kruyswijk, MD,c and Rein Willemze, MDa Amsterdam and Enschede,
The Netherlands We report the cases of four patients who were taking the anticonvulsant drugs phenytoin or carbamazepine and in whom skin lesions developed that showed histologic features suggestive of mycosis fungoides. Two patients had a solitary lesion on the trunk, whereas the other two patients had multiple plaques. In all four patients systemic signs were absent. (J AM ACAD DERMATOL 1991;24:216-20.)
Pseudolymphomatolls reactions to the anticonvulsantdrugs phenytoin and carbamazepine have been frequently reported. l - lO These patients often have the triad of lymphadenopathy, fever, and a generalized skin eruption. The suspicion of lymphoma is usually based on the clinical features and the histologic changes in affected lymph nodes. loS Only siX patients have been described in whom histologic examination of the skin showed features suggestive of mycosis fungoides (MF). All these patients were taking phenytoin and five had a generalized sldn eruption, fever, and lymphadenopathy.6-IO The other patient had several MF-like plaques and lymphadenopathy but no fever. IO We report the cases Of four patients"in whom cutaneous MF-like lesions developed without systemic signs or symptoms during therll.py with phenytoin or carbamazepine.
CASE REPORTS
Case 1 A 42-year-old woman was seen in February 1984 with a slightly scaling, infiltrated, red, 1.5 X 2.5 em plaque on her back, which had been present for several months (Fig. 1). General physical examination was unremarkable. Because of epilepsy after a stroke in 1981, she was taking
From the Departments of Dermatology' and Pathology,b Free University Hospital, Amsterdam; and the Department of Dermatology, Enschede Hospitals.c Accepted fOT publication Aug. I, 1990. Reprint requests: J. U. Rijlaarsdam, MD, Department of Dermatology, Free University Hospital, De Boelelaan 1117, l081 HV Amsterdam, The Netherlands.
16/1/24279
216
phenytoin, acetylsalicylic acid, and dipyridamole. After an initial biopsy specimen showed features suggestive of MF, the lesion was excised completely. Histologic examination showed a dense subepidermal bandlike infiltrate that extended around some hair follicles (Fig. 2). The infiltrate consisted mainly of atypical mononuclear cells with medium-sized cerebriform nuclei and a few blast cells (Fig. 3). Only moderate numbers of histiocytes were present and eosinophi1s and plasma cells were not seen. There was focal infiltration of the epidermis with atypical cells, without formation of Pautrier's microabscesses. Few mitoses were present. ImrilUnohistochemical analysis showed a predominanceof CD2+, CD3+, CDS+ T cells, with a major predominance of CD4+ cells (CD4/CD8 ratio 4:1). Less than 10% of the infiltrating cells stained with anti-Leu-8. The T cells stained diffusely with anti-HLA-DR. Staining for CD30 (Ki-1) antigens was completely negative. In the dermal infiltrate approximately 10% of Leu-MS+ macrophages and 5% of CD1 + Langerhans cells were present. Electron microscopy showed many large lymphocytes with highly convoluted nuclei (Fig. 4). Morphometric analysis showed high nuclear contour index (NCI) values for these lymphocytes, with 12% of the cells having an NCI of more than 11.5. Similar findings have been published for patients with MF. 11 The patient showed no signs of MFafter a 5-year follOW-Up period. The use of phenytoin and the other drugs was continued.
Case 2 A 43-year-old man was seen in February 1988 with an oval, 1.2 X 1.8 cm, infiltrated plaque on the chest that had been present for several months. The patient had used carbamazepine for epilepsy since 1982. After an initial biopsy the lesion was excised completely. The results of
Volume 24 Number 2, Part I February) 991
Mycosis jungoides-/ike drug eruption 217
Fig. I. Case 1. Slightly scaling, infiltrated 1.5 X 2.5 cm lesion on the back.
.Fig. 2. Dense subepidermal bandlike infiltrate. Infiltration of epidermis is relatively sparse. (X40.)
routine histologic examination, immunohistochemical analysis, and morphometry were similar to those described for patient I and were considered consistent with the diagnosis MF. On follow-up the patient showed no signs of MF. He was continuing to take carbamazepine.
Case 3 An 80-year-old man was seen in October 1989 with many nummular infiltrated plaques on the trunk that had been present for several months. These skin lesions had been unsuccessfully treated with topical steroids. Exam-
ination did not reveal any palpable lymph nodes. Iri addition to the phenytoin that he had been taking for 1 year, the patient was also taking acetylsalicylic acid, dipyridamole, prazosin, and hydrochlorothiazide. The results of routine histologic and immunohistochemical examination were similar to those described in patient 1. Because clinically and histologically a diagnosis of MF or a drug-induced cutaneous pseudolymphoma was considered, the phenytoin use was discontinued. This resulted in complete clearance of the skin lesions within 3 weeks.
Journal of the American Academy of Dermatology
218 Rijlaarsdam et al.
Fig. 3. Infiltrate is composed of mononuclear cells with large cerebriform nuclei and occasional blast cells. (X360.)
Fig. 4. Case 1. Electron micrograph shows large lymphocytes with highly convoluted nuclei. (X5400.)
Case 4
DISCUSSION
A 36-year-old woman was seen in February 1989 with three slightly scaling plaques on the left breast and the abdomen that had been present for several months. Further examination was unremarkable. The patient had been taking carbamazepine for epilepsy. Histologic examination of one of the plaques showed the same features as in case 1 and was suggestive of MF. The skin lesions did not respond to therapy with topical betamethasone valerate. However, when carbamazepine was replaced by phenytoin, the skin lesions cleared completely and after 1 year of follow-up, there has been no relapse.
We have described four patients who were taking anticonvulsant drugs who had skin lesions that showed histologic features suggestive of MF. In two of these patients (cases 3 and 4) there was strong evidence of a causal relation between the skin lesions and the use of phenytoin and carbamazepine. Whereas topical steroids did not produce any improvement, discontinuation of these drugs resulted in complete clearance. In the other two patients (cases 1 and 2) we cannot prove a causal relation
Volume 24 Number 2, Part I February 1991
between the solitary skin lesions and therapy with phenytoin or carbamazepine. In both of these patients the anticonvulsant medication was continued. Because solitary pseudo-MF lesions are extremely rare, we believe the association is more than a coincidence. The histologic features of the four patients were strikingly similar. All cases showed an infiltrate of lymphoid cells with medium-sized cerebriform nuclei with occasional blast cells but few admixed inflammatory cells. In the epidermis only a few atypical lymphocytes were seen, without the formation of Pautrier's microabscesses. Although the histologic features were highly suggestive of MF, there were some differences from classical plaque-stage MF that is often characterized by a polymorphous bandlike infiltrate, with atypical lymphocytes with large cerebriform nuclei admixed with smalllymphocytes, occasional plasma cells and eosinophils, and often marked epidermotropism of atypical cells with or without Pautrier's microabscess formation. 12 Although pseudolymphomatous reactions to phenytoin and carbamazepine have been frequently reported, MF-like lesions have been described in only six patients who were taking phenytoin. 6 - 10 Histologically, these cases showed marked epidermotropism with Pautrier's microabscess formation in four cases. In contrast, our patients had only MFlike lesions without associated lymphadenopathy or fever. The two patients in whom MF-like lesions developed during carbamazepine therapy show that this drug can induce both a systemic pseudolymphomatous reaction and a localized cutaneous pseudolymphoma. Two patients (cases 1 and 2) had a solitary MFlike lesion. Similar lesions, not associated with anticonvulsant therapy, have been described by Oliver and Winkelmann 13 and Van der Putte et a1. 14 Oliver and Winkelmann described four patients who had a solitary plaque with histologic features of MF, under the diagnosis of unilesional MF. In this report drug use was not recorded for all four patients. Histologically, the epidermotropism of the atypical cells was more pronounced in these patients than in our group; Pautrier's microabscess formation was present in two of them. Van der Putte et al. I4 described three patients with a solitary nonepidermotropic T-cell pseudolymphoma. These patients had a solitary lesion on the trunk but were not taking anticonvulsant medication. Infiltration of the epidermis was totally absent and the bandlike infiltrate
Mycosis fungoides-like drug eruption 219 of atypical mononuclear cells was separated from the epidermis by a cell-free grenz zone. The morphologic features of the atypical cells were indistinguishable from those in MF, and with cytomorphometric analysis the infiltrate was classified as malignant. In our two patients with a solitary MF-like lesion, the diagnosis of pseudolymphoma is highly likely because of the clinical presentation, the uneventful follow-up, and the concomitant use of drugs known to induce pseudolymphomas. However, in patients with more widespread skin disease, as in cases ,3 and 4, and in particular in patients with erythroderma who have the histologic features of MF, the possibility of a MF-like drug eruption must be considered. In addition to anticonvulsant drugs, angiotensin-converting enzyme inhibitors and several other drugs (atenolol, mexiletine, thioridazine, D-penicillamine, moduretic) have been mentioned to induce these MF-like drug eruptions. IS-I? In these cases discontinuation of the offending drug may lead to the correct diagnosis and prevent unnecessary aggressive treatment. REFERENCES 1. Charlesworth EN. Phenytoin-induced pseudolymphoma syndrome. Arch Dermatol 1977;113:477-80. 2. Gams RA, Neal lA, Conrad FG. Hydantoin-induced pseudo-pseudolymphoma. Ann Intern Moo 1968;69:55768. 3. Schuttleworth D, Graham-Brown RAC, Williams Al, et al. Pseudo-lymphoma associated with carbamazepine. Clin Exp DermatoI1984;9:421-3. 4. Yates P, Stockdill G, McIntyre M. Hypersensitivity to carbamazepine presenting as pseudolymphoma. 1 Clin Pathol 1986;39:1224-8. 5. Taylor MW, Smith CC, Hern lEC. An unexpected reaction to carbamazepine. Practitioner 1981;225:219-20. 6. Schreiber MM, McGregor lG. Pseudolymphoma syndrome. Arch DermatoI1968;97:297-300. 7. Rosenthal Cl, Noguera CA, Coppola A, et al. Pseudolymphoma with mycosis fungoides manifestations, hyperresponsiveness to diphenylhydantoin and lymphocyte disregulation. Cancer 1982;49:2305-14. 8. Souteyrand P, D'Incan M. Drug induced mycosis fungoides-like lesions. In: Van V10ten WA, Willemze R, Lange Vejlsgaard G, et aI, eds. Cutaneous lymphoma. Curr Prabl DermatoI1990;19:176-82. 9. Cooke LE, Hardin TC, Hendrickson DJ. Phenytoin-induced pseudolymphoma with mycosis fungoides manifestations. Clin Pharm 1988;7:153-7. 10. Wolf R, Kahane E, Sandbank M. Mycosis fungoides-like lesions associated with phenytoin therapy. Arch Dermatol 1985;121:1181-2. 11. Van der Loo EM, Van Vloten WA, Cornelisse CJ, et al. The relevance of morphometry in the differential diagnosis of cutaneous T cell lymphoma. Br J Dermatol 1981;104: 257-69. 12. NickoloffBl. Light-microscopic assessment of 100 patien~"
Journal of the American Academy of
Rijlaarsdam et al. with patch/plaque-stage mycosis fungoides. Am J Dermatopathol 1988;10:469-77. 13. Oliver OF, Winkelmann RK. Unilesional mycosis fungoides: a distinct entity. J AM ACAD DERMATOL 1989;20:6370.
van der Putte SCJ, Toonstra J, Felten PC, et al. Solitary nonepidermotropic T cell pseudolymphoma of the skin. J AM ACAD DERMATOL 1986;14:444-53. 15. Furness PN, Goodfield MJ, MacLennan KA, et al. Severe 14.
Dermatology
cutaneous reactions to captopril and enalapril: histological study and comparison with early mycosis fungoides. J Clin Pathol 1986;39:902-7. 16. Henderson CA, Shamy HK. Atenolol-induced pseudolymphoma. Clin Exp Dermatol 1990;15:119-20. 17. Kardaun SH, Scheffer E, Vermeer BJ. Drug-induced pseudolymphomatous skin reactions. Br J Dermatol 1988;118:545-52.
Dopa reaction test in hair bulbs of fetuses and its application to the prenatal diagnosis of albinism Ruth Gershoni-Baruch, MD,a Avraham Benderly, MD,a Joseph M. Brandes, MD,b and Amos Gilhar, MDC Haifa, Israel No information is available on the amount of tyrosinase normally present in fetuses. A dopa reaction test in hair bulbs from the scalp of normal fetuses obtained after abortion showed that tyrosinase is present in fetuses as early as 17 weeks. Only faint activity was detected in skin specimens other than from the scalp. This assay can serve as a quick and reliable method for the prenatal diagnosis of tyrosinase-negative albinism. (J AM ACAD DERMATOL 1991;24:220-2.)
Oculocutaneous albinism (OCA) is a rare autosomal recessive disorder of melanin metabolism characterized by hypopigmentationof hair, skin, and eyes. 1 At least 10 variants of OCA have been described. 2 The most common are tyrosinase-positive and tyrosinase-negative albinism, so designated to denote partial or total absence of tyrosinase in the melanocytes. 3 Tyrosinase-negative OCA is the most hypopigmentedform and is characterized bymarked photosensitivity to sunlight that leads to severe burning, wrinkling, solar elastosis, and various malignancies. In 1981 Haynes and Robertson 4 extended the idea of prenatal diagnosis in OCA by fetoscopy be-
tween the sixteenth and twentieth weeks of pregnancy. Electron microscopy (EM) showed fully developed melanosomes in samples of scalp hair from 12 aborted fetuses. Eady et al. 5 detected OCA prenatally by electron microscopic examination of scalp samples obtained from a 20-week-old fetus by fetoscopy. Because melanin is not present in amniotic cells, only melanocytes from hair bulb and skin can provide the diagnosis. There is no informationon the amount of tyrosinase in normal fetuses. In this study the maturity of the tyrosinase system has been assessed by the dopa reaction in hair bulbs from skin samples of fetuses at different gestational ages. SUBJECTS AND METHODS
From the Department ofPediatrics· and the Department of Obstetrics and Gynecology,b Rambam Medical Center; and the Laboratory of Skin Research,c Faculty ofMedicine, Technion·' band the Rappoport Institute of Medical Research,b Supported by the Technion Vice President for Research Fund-Albert Goodstein Research Fund. Accepted for publication Aug. 4, 1990. Reprint requests: R. Gershoni-Baruch, MD, Department of Pediatrics, Rambam Medical Center, P.O.B. 9602,31096 Haifa, Israel. 16/1/25308
220
Three millimeter punch biopsy specimens were obtained at autopsy from 19 fetuses after prostaglandin-induced termination of pregnancy. Indications for the termination of pregnancies were determined by a government committee. Gestational ages ranged from 12 to 30 weeks (Table I). Skin samples were taken from the scalp and the back. In two cases an additional specimen was obtained from the thigh, The gestational age was based on menstrual history and ultrasound findings.
The Netherlands We report the cases of four patients who were taking the anticonvulsant drugs phenytoin or carbamazepine and in whom skin lesions developed that showed histologic features suggestive of mycosis fungoides. Two patients had a solitary lesion on the trunk, whereas the other two patients had multiple plaques. In all four patients systemic signs were absent. (J AM ACAD DERMATOL 1991;24:216-20.)
Pseudolymphomatolls reactions to the anticonvulsantdrugs phenytoin and carbamazepine have been frequently reported. l - lO These patients often have the triad of lymphadenopathy, fever, and a generalized skin eruption. The suspicion of lymphoma is usually based on the clinical features and the histologic changes in affected lymph nodes. loS Only siX patients have been described in whom histologic examination of the skin showed features suggestive of mycosis fungoides (MF). All these patients were taking phenytoin and five had a generalized sldn eruption, fever, and lymphadenopathy.6-IO The other patient had several MF-like plaques and lymphadenopathy but no fever. IO We report the cases Of four patients"in whom cutaneous MF-like lesions developed without systemic signs or symptoms during therll.py with phenytoin or carbamazepine.
CASE REPORTS
Case 1 A 42-year-old woman was seen in February 1984 with a slightly scaling, infiltrated, red, 1.5 X 2.5 em plaque on her back, which had been present for several months (Fig. 1). General physical examination was unremarkable. Because of epilepsy after a stroke in 1981, she was taking
From the Departments of Dermatology' and Pathology,b Free University Hospital, Amsterdam; and the Department of Dermatology, Enschede Hospitals.c Accepted fOT publication Aug. I, 1990. Reprint requests: J. U. Rijlaarsdam, MD, Department of Dermatology, Free University Hospital, De Boelelaan 1117, l081 HV Amsterdam, The Netherlands.
16/1/24279
216
phenytoin, acetylsalicylic acid, and dipyridamole. After an initial biopsy specimen showed features suggestive of MF, the lesion was excised completely. Histologic examination showed a dense subepidermal bandlike infiltrate that extended around some hair follicles (Fig. 2). The infiltrate consisted mainly of atypical mononuclear cells with medium-sized cerebriform nuclei and a few blast cells (Fig. 3). Only moderate numbers of histiocytes were present and eosinophi1s and plasma cells were not seen. There was focal infiltration of the epidermis with atypical cells, without formation of Pautrier's microabscesses. Few mitoses were present. ImrilUnohistochemical analysis showed a predominanceof CD2+, CD3+, CDS+ T cells, with a major predominance of CD4+ cells (CD4/CD8 ratio 4:1). Less than 10% of the infiltrating cells stained with anti-Leu-8. The T cells stained diffusely with anti-HLA-DR. Staining for CD30 (Ki-1) antigens was completely negative. In the dermal infiltrate approximately 10% of Leu-MS+ macrophages and 5% of CD1 + Langerhans cells were present. Electron microscopy showed many large lymphocytes with highly convoluted nuclei (Fig. 4). Morphometric analysis showed high nuclear contour index (NCI) values for these lymphocytes, with 12% of the cells having an NCI of more than 11.5. Similar findings have been published for patients with MF. 11 The patient showed no signs of MFafter a 5-year follOW-Up period. The use of phenytoin and the other drugs was continued.
Case 2 A 43-year-old man was seen in February 1988 with an oval, 1.2 X 1.8 cm, infiltrated plaque on the chest that had been present for several months. The patient had used carbamazepine for epilepsy since 1982. After an initial biopsy the lesion was excised completely. The results of
Volume 24 Number 2, Part I February) 991
Mycosis jungoides-/ike drug eruption 217
Fig. I. Case 1. Slightly scaling, infiltrated 1.5 X 2.5 cm lesion on the back.
.Fig. 2. Dense subepidermal bandlike infiltrate. Infiltration of epidermis is relatively sparse. (X40.)
routine histologic examination, immunohistochemical analysis, and morphometry were similar to those described for patient I and were considered consistent with the diagnosis MF. On follow-up the patient showed no signs of MF. He was continuing to take carbamazepine.
Case 3 An 80-year-old man was seen in October 1989 with many nummular infiltrated plaques on the trunk that had been present for several months. These skin lesions had been unsuccessfully treated with topical steroids. Exam-
ination did not reveal any palpable lymph nodes. Iri addition to the phenytoin that he had been taking for 1 year, the patient was also taking acetylsalicylic acid, dipyridamole, prazosin, and hydrochlorothiazide. The results of routine histologic and immunohistochemical examination were similar to those described in patient 1. Because clinically and histologically a diagnosis of MF or a drug-induced cutaneous pseudolymphoma was considered, the phenytoin use was discontinued. This resulted in complete clearance of the skin lesions within 3 weeks.
Journal of the American Academy of Dermatology
218 Rijlaarsdam et al.
Fig. 3. Infiltrate is composed of mononuclear cells with large cerebriform nuclei and occasional blast cells. (X360.)
Fig. 4. Case 1. Electron micrograph shows large lymphocytes with highly convoluted nuclei. (X5400.)
Case 4
DISCUSSION
A 36-year-old woman was seen in February 1989 with three slightly scaling plaques on the left breast and the abdomen that had been present for several months. Further examination was unremarkable. The patient had been taking carbamazepine for epilepsy. Histologic examination of one of the plaques showed the same features as in case 1 and was suggestive of MF. The skin lesions did not respond to therapy with topical betamethasone valerate. However, when carbamazepine was replaced by phenytoin, the skin lesions cleared completely and after 1 year of follow-up, there has been no relapse.
We have described four patients who were taking anticonvulsant drugs who had skin lesions that showed histologic features suggestive of MF. In two of these patients (cases 3 and 4) there was strong evidence of a causal relation between the skin lesions and the use of phenytoin and carbamazepine. Whereas topical steroids did not produce any improvement, discontinuation of these drugs resulted in complete clearance. In the other two patients (cases 1 and 2) we cannot prove a causal relation
Volume 24 Number 2, Part I February 1991
between the solitary skin lesions and therapy with phenytoin or carbamazepine. In both of these patients the anticonvulsant medication was continued. Because solitary pseudo-MF lesions are extremely rare, we believe the association is more than a coincidence. The histologic features of the four patients were strikingly similar. All cases showed an infiltrate of lymphoid cells with medium-sized cerebriform nuclei with occasional blast cells but few admixed inflammatory cells. In the epidermis only a few atypical lymphocytes were seen, without the formation of Pautrier's microabscesses. Although the histologic features were highly suggestive of MF, there were some differences from classical plaque-stage MF that is often characterized by a polymorphous bandlike infiltrate, with atypical lymphocytes with large cerebriform nuclei admixed with smalllymphocytes, occasional plasma cells and eosinophils, and often marked epidermotropism of atypical cells with or without Pautrier's microabscess formation. 12 Although pseudolymphomatous reactions to phenytoin and carbamazepine have been frequently reported, MF-like lesions have been described in only six patients who were taking phenytoin. 6 - 10 Histologically, these cases showed marked epidermotropism with Pautrier's microabscess formation in four cases. In contrast, our patients had only MFlike lesions without associated lymphadenopathy or fever. The two patients in whom MF-like lesions developed during carbamazepine therapy show that this drug can induce both a systemic pseudolymphomatous reaction and a localized cutaneous pseudolymphoma. Two patients (cases 1 and 2) had a solitary MFlike lesion. Similar lesions, not associated with anticonvulsant therapy, have been described by Oliver and Winkelmann 13 and Van der Putte et a1. 14 Oliver and Winkelmann described four patients who had a solitary plaque with histologic features of MF, under the diagnosis of unilesional MF. In this report drug use was not recorded for all four patients. Histologically, the epidermotropism of the atypical cells was more pronounced in these patients than in our group; Pautrier's microabscess formation was present in two of them. Van der Putte et al. I4 described three patients with a solitary nonepidermotropic T-cell pseudolymphoma. These patients had a solitary lesion on the trunk but were not taking anticonvulsant medication. Infiltration of the epidermis was totally absent and the bandlike infiltrate
Mycosis fungoides-like drug eruption 219 of atypical mononuclear cells was separated from the epidermis by a cell-free grenz zone. The morphologic features of the atypical cells were indistinguishable from those in MF, and with cytomorphometric analysis the infiltrate was classified as malignant. In our two patients with a solitary MF-like lesion, the diagnosis of pseudolymphoma is highly likely because of the clinical presentation, the uneventful follow-up, and the concomitant use of drugs known to induce pseudolymphomas. However, in patients with more widespread skin disease, as in cases ,3 and 4, and in particular in patients with erythroderma who have the histologic features of MF, the possibility of a MF-like drug eruption must be considered. In addition to anticonvulsant drugs, angiotensin-converting enzyme inhibitors and several other drugs (atenolol, mexiletine, thioridazine, D-penicillamine, moduretic) have been mentioned to induce these MF-like drug eruptions. IS-I? In these cases discontinuation of the offending drug may lead to the correct diagnosis and prevent unnecessary aggressive treatment. REFERENCES 1. Charlesworth EN. Phenytoin-induced pseudolymphoma syndrome. Arch Dermatol 1977;113:477-80. 2. Gams RA, Neal lA, Conrad FG. Hydantoin-induced pseudo-pseudolymphoma. Ann Intern Moo 1968;69:55768. 3. Schuttleworth D, Graham-Brown RAC, Williams Al, et al. Pseudo-lymphoma associated with carbamazepine. Clin Exp DermatoI1984;9:421-3. 4. Yates P, Stockdill G, McIntyre M. Hypersensitivity to carbamazepine presenting as pseudolymphoma. 1 Clin Pathol 1986;39:1224-8. 5. Taylor MW, Smith CC, Hern lEC. An unexpected reaction to carbamazepine. Practitioner 1981;225:219-20. 6. Schreiber MM, McGregor lG. Pseudolymphoma syndrome. Arch DermatoI1968;97:297-300. 7. Rosenthal Cl, Noguera CA, Coppola A, et al. Pseudolymphoma with mycosis fungoides manifestations, hyperresponsiveness to diphenylhydantoin and lymphocyte disregulation. Cancer 1982;49:2305-14. 8. Souteyrand P, D'Incan M. Drug induced mycosis fungoides-like lesions. In: Van V10ten WA, Willemze R, Lange Vejlsgaard G, et aI, eds. Cutaneous lymphoma. Curr Prabl DermatoI1990;19:176-82. 9. Cooke LE, Hardin TC, Hendrickson DJ. Phenytoin-induced pseudolymphoma with mycosis fungoides manifestations. Clin Pharm 1988;7:153-7. 10. Wolf R, Kahane E, Sandbank M. Mycosis fungoides-like lesions associated with phenytoin therapy. Arch Dermatol 1985;121:1181-2. 11. Van der Loo EM, Van Vloten WA, Cornelisse CJ, et al. The relevance of morphometry in the differential diagnosis of cutaneous T cell lymphoma. Br J Dermatol 1981;104: 257-69. 12. NickoloffBl. Light-microscopic assessment of 100 patien~"
Journal of the American Academy of
Rijlaarsdam et al. with patch/plaque-stage mycosis fungoides. Am J Dermatopathol 1988;10:469-77. 13. Oliver OF, Winkelmann RK. Unilesional mycosis fungoides: a distinct entity. J AM ACAD DERMATOL 1989;20:6370.
van der Putte SCJ, Toonstra J, Felten PC, et al. Solitary nonepidermotropic T cell pseudolymphoma of the skin. J AM ACAD DERMATOL 1986;14:444-53. 15. Furness PN, Goodfield MJ, MacLennan KA, et al. Severe 14.
Dermatology
cutaneous reactions to captopril and enalapril: histological study and comparison with early mycosis fungoides. J Clin Pathol 1986;39:902-7. 16. Henderson CA, Shamy HK. Atenolol-induced pseudolymphoma. Clin Exp Dermatol 1990;15:119-20. 17. Kardaun SH, Scheffer E, Vermeer BJ. Drug-induced pseudolymphomatous skin reactions. Br J Dermatol 1988;118:545-52.
Dopa reaction test in hair bulbs of fetuses and its application to the prenatal diagnosis of albinism Ruth Gershoni-Baruch, MD,a Avraham Benderly, MD,a Joseph M. Brandes, MD,b and Amos Gilhar, MDC Haifa, Israel No information is available on the amount of tyrosinase normally present in fetuses. A dopa reaction test in hair bulbs from the scalp of normal fetuses obtained after abortion showed that tyrosinase is present in fetuses as early as 17 weeks. Only faint activity was detected in skin specimens other than from the scalp. This assay can serve as a quick and reliable method for the prenatal diagnosis of tyrosinase-negative albinism. (J AM ACAD DERMATOL 1991;24:220-2.)
Oculocutaneous albinism (OCA) is a rare autosomal recessive disorder of melanin metabolism characterized by hypopigmentationof hair, skin, and eyes. 1 At least 10 variants of OCA have been described. 2 The most common are tyrosinase-positive and tyrosinase-negative albinism, so designated to denote partial or total absence of tyrosinase in the melanocytes. 3 Tyrosinase-negative OCA is the most hypopigmentedform and is characterized bymarked photosensitivity to sunlight that leads to severe burning, wrinkling, solar elastosis, and various malignancies. In 1981 Haynes and Robertson 4 extended the idea of prenatal diagnosis in OCA by fetoscopy be-
tween the sixteenth and twentieth weeks of pregnancy. Electron microscopy (EM) showed fully developed melanosomes in samples of scalp hair from 12 aborted fetuses. Eady et al. 5 detected OCA prenatally by electron microscopic examination of scalp samples obtained from a 20-week-old fetus by fetoscopy. Because melanin is not present in amniotic cells, only melanocytes from hair bulb and skin can provide the diagnosis. There is no informationon the amount of tyrosinase in normal fetuses. In this study the maturity of the tyrosinase system has been assessed by the dopa reaction in hair bulbs from skin samples of fetuses at different gestational ages. SUBJECTS AND METHODS
From the Department ofPediatrics· and the Department of Obstetrics and Gynecology,b Rambam Medical Center; and the Laboratory of Skin Research,c Faculty ofMedicine, Technion·' band the Rappoport Institute of Medical Research,b Supported by the Technion Vice President for Research Fund-Albert Goodstein Research Fund. Accepted for publication Aug. 4, 1990. Reprint requests: R. Gershoni-Baruch, MD, Department of Pediatrics, Rambam Medical Center, P.O.B. 9602,31096 Haifa, Israel. 16/1/25308
220
Three millimeter punch biopsy specimens were obtained at autopsy from 19 fetuses after prostaglandin-induced termination of pregnancy. Indications for the termination of pregnancies were determined by a government committee. Gestational ages ranged from 12 to 30 weeks (Table I). Skin samples were taken from the scalp and the back. In two cases an additional specimen was obtained from the thigh, The gestational age was based on menstrual history and ultrasound findings.