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Heat stable E-receptors on leukemic lymphoblasts in ataxia-telangiectasia
Volume 91 Number 2
could be misjudged, if thyroid function is not monitored. For these reasons, children with Turner syndrome should be periodically evaluated for normalcy of their thyroid function. The authors thank MI. G, Henry, Mrs. J. Clark, Ms. N. Lightman, and Mrs. B. Threadgill for technical and secretarial assistance.
REFERENCES I.
Sparkes RS, and Motulsky AB: Hashimoto's disease in Turner's syndrome with isochromosone X, Lancet 1:947, 1963. 2. Williams ED, and Forbes AP: Thyroiditis and gonadal dysgenesis, N Engl J Med 270:805, 1964.
Heat stable E-receptors on leukemic lymphoblasts in ataxiatelangiectasia Eric Cameron, M.D., Rama S. Seshadri, M.D., M.R.A.C.P., K. R. Mohan Pai, M.D., F.R.C.P.(C),
and Peter B. Dent, M.D., F.R.C.P.(C),* Hamilton, Ont,, Canada
A T A X I A - T E L A N G I E C T A S I A is a Complex syndrome; consistent and striking central nervous system degenerative changes occur which are often associated with variable defects in humoral and cellular immunity, x''-' Lymphoreticular and nonlymphoid malignancy are estimated to occur in 10% of the patients? In this report, we describe a 12-year-old boy with ataxia-telangiectasia who developed acute lymphoblastic leukemia in w h o m we have characterized the lymphoblasts as having heat-stable sheep erythrocyte receptors.
CASE REPORT Patient H. V. was diagnosed to have ataxia-telangiectasia at the age of 7 years on the basis of ataxia, conjunctival telangiectases, and frequent respiratory infection. He had no IgA, a low lymphocyte level, negative skin tests, and a depressed PHA *Reprint address: McMaster University Medical Centre, Department of Pediatrics, Room 4H17, 1200 Main Street West, Hamilton, Ont., Canada.
B r i e f clinical and laboratory observations
269
3. Engel E, and Forbes AP: Cytogenetic and clinical findings in 48 patients with congenitally defective or absent ovaries, Medicine 44:135, 1965. 4. Grumbach MM~ and Morishima A:X-chromosome abnormalities in gonadal dysgenesis: DNA replication of structurally abnormal X-chromosomes; relation to thyroid disease, J PEDIATR65:1087, 1964 (abstr). 5. Rallison ML, Debyns BM, Rail JE, and Tyler FH: Occurrence and natural history of chronic lymphocytic thyroiditis in childhood, J PEDIATR86:675, 1975. 6. Leboeuf G, and Ducharme JR: Thyroiditis in children, diagnosis and management, Pediatr Clin North Am 13:19, 1966. 7. Hill OW: Thyroglobulin antibodies in 1,297 patients without thyroid disease, Br Med J 1:1793, 1961.
response. At age 12 he presented with a three-month history of pallor, malaise, fever, and progressive neurologic deterioration. The hemoglobulin concentration was 4.0 gm/dl, WBC 22,700/ mm ~with 99% abnormal mononuclear cells and platelet count of 17,000/ram ~. Peripheral blood smear revealed two populations of abnormal mononuclear cells. One population consisted of small ceils with high nuclear-cytoplasmic ratio and indistinct nucleoli. Some of these small cells showed clefting of the nuclei. Cytoplasm was scant and there were no granules. The second population consisted of large cells with a moderate amount of cytoplasm and an immature nucleus containing one or two distinct nucleoli. The cytoplasm was blue in color and had no granules. The large cell population formed approximately 10% of the abnormal mononuclear cells. Abbreviations used AT: ataxia-telangiectasi a PHA: phytohemagglutinin E: sheep erythrocyte WBC: white blood count Hgb: hemoglobin A bone marrow aspirate showed complete replacement of normal cellular elements by abnormal mononuclear cells similar to those found in the peripheral blood. The morphology of the cells was considered to be atypical for acute lymphoblastic leukemia (Fig. 1). Periodic acid-Schiff stain of the peripheral blood and bone marrow cells revealed no positive reaction. The peroxidase stain was also negative. The results of lymphocyte studies done during the course of the illness are shown in Table I. When first seen in April, 1971, at age 7 years he had a low normal level of peripheral blood lymphocytes with a depressed response to PHA in vitro, using a whole blood microculture technique with optimal and threshold concentrations of mitogen2 At the time of diagnosis of leukemia on April 6, 1976, peripheral blood mononuclear cells were isolated on Ficoll-hypaque gradients and the percentage of cells rosetting with sheep erythrocytes at 0~ and 37~ was deter-
270
Brief clinical and laboratory observations
The Journal of Pediatrics August 1977
Table I. Results of immunologic investigations
Date April 13, 1971 Total lymphocytes (mm~)
1,152
Peripheral blood E- rosettes (%) 0~ ND 37 ~ ND Bone marrow E-rosettes (%) 0~ ND 37 ~ Lymphocyte stimulation (cpm :'H-thymidine incorporation) PHA l0 ~tg/ml 1,028 ( > 10,000) PHA 0.3/~g/ml 1,414 ( > 2,000) Unstimulated 52 ( < 200)
April 6, 1976 22,000 abnormal mononuclear
[
April 27, 1976
I
June 6, 1976
7,968
133
80 (63)* 70 (16)
20 (63) 1 (1)
ND ND
88 75
ND
ND
4,333 4,469 4,004
28,186 1,220 425
81 55 31
*Figures in brackets represent normal adult controls.
and 6-mercaptopurine (50 mg/m2/week) but the patient developed pneumonia unresponsive to antibiotics about two weeks later. On June 6, 1976, four weeks after the start of the maintenance schedule the complete blood count was as follows: Hgb 6.2 gm/dl; platelets 70,000/mm~; WBC 1,900/mm a with 83% neutrophils, 9% band forms, 2.% eosinophils, and 7% lymphocytes. There was a marked suppression of his lymphocyte stimulation response (Table I). The patient died 11 weeks aft.er the initial diagnosis of acute lymphoblastic leukemia. At autopsy the thymus and lymphoid tissues were hypoplastic and dysplastic, lntranuclear inclusion bodies were present in numerous organs compatible with widespread cytomegalovirus infection. FiR. 1. Bone marrow aspirate showing the two morphologic types of abnormal lymphoid cells: the predominant small cell with high nu~zlear cytoplasmic ratio and the larger cell with more abundant cytoplasm and immature nucleus (magnification 800 x ). mined? Seventy percent (70%) formed heat stable rosettes as compared with 16% of cells from a normal control individual. Seventy-five percent (75%) of the bone marrow mononuclear cells isolated in a similar fashion formed heat stable E rosettes. In vitro lymphocyte cultures showed a high unstimulated value of 3H-thymidine uptake compatible with large numbers of rapidly dividing cells in the peripheral blood. ~ There was no increase in :'H-thymidine uptake in cultures containing PHA. He was treated with vincristine (l.5 mg/m ~ weekly) and prednisone (50 mg/m ~ daily). On April 27, 1976, three weeks after the start of chemotherapy h e was in remission as judged by peripheral blood smear. Complete Nodd count revealed: Hgb 12.4 gm/dl; WBC 16,600/mm ~ with 5% myelocytes, 3% metamyelocytes, 15% band forms, 63% neutrophils, 45% lymphocytes, and 4% monocytes. Platelet count was 369 000/mm ~. A repeat of the lymphocyt e stimulation showed a normal response to optimal concentration of PHA. Repeat E-rosette studies showed 20% at 0 ~ and 0% at 37~ Therapy was maintained with m ethotrexate (20 mg/mVweek)
COMMENT The precise nature of the defect in AT is poorly understood. The abnormality is clearly not limited to the lymphoid system but appears to be a fundamental defect in cellular differentiation affecting thymus, central nervous system, blood vessels, and gonadsF The finding of elevated levels of alpha fetoprotein in patients with A T is consistent with this hypothesis. 7 In our patient both alpha fetoprotein and the carcinoembryonic antigen* levels were e l e v a t e d - 4 0 0 n g / m l and 10.7 ng/ml, respectively. These patients' susceptibility to neoplasia is well known and may relate as much to the fundamental defect as to the associated imraunodeficiency. The uniqueness of this report is the finding of receptors for sheep erythrocytes on the a b n o r m a l cells in blood and bone marrow, which permit the further definition of the neoplasia as a T cell leukemia. The heat stability of the rosetting lymphocytes differentiates these cells from mature peripheral blood T cells? This temperature independence has been shown to be characteristic of undifferentiated normal T cells within the thymus as well as
Volume 91 Number 2
Brief cfinical and laboratory observations
leukemic l y m p h o b l a s t s o f the T cell variety? It is o f interest that as the patient went into remission the blood m o n o n u c l e a r cell E-rosettes [ost their heat stability a n d showed i m p r o v e d responsiveness to P H A indicating a disappearance o f the a b n o r m a l lymphoblasts, The designation of the leukemia in our patient as T cell in nature is of interest because of the previously described functional a n d morpholog~c thymic a b n o r m a l i t i e s in ataxia-telangiectasia. As indicated above the pathogenesis of the thymic a b n o r m a l i t i e s is not k n o w n a l t h o u g h it has been postulated that a defect in the thymic e p i t h e l i u m m a y be responsible for the a b n o r m a l l y m p h o c y t e function. It is interesting to speculate that the h e i g h t e n e d susceptibility of A T lymphocytes to neoplastic transform a t i o n m a y be secondary to the chronic inability o f the T cells to undergo complete m a t u r a t i o n .
2.
REFERENCES
8.
3.
4.
5.
6.
7.
271
Peterson RDA, Cooper MD, and Good RA: Lymphoid tissue abnormalities associated with ataxia-telangiectasia, Am J Med 41:342, 1966. Kersey JH, Spector BD, and Good RA: Primary immunodeficiency diseases and cancer: The immunodeficiencycancer registry, lnt J Cancer 12:333, 1973. Lui VK, Karpuchas J, Dent PB, McCulloch PB, and Blajchman MA: Cellular immunocompetence in melanoma: Effect of extent of disease and immunotherapy, Br J Cancer 32:323, 1975. Borella L, and Sen L: E receptors on blasts from untreated acute lymphocytic leukemia: Comparison of temperature dependence of E rosettes formed by normal and leukemic lymphoid cells, J Immunol 114:187, 1975. Rubini JR, Bond VP, Keller S, Fliedner TM, and Cronkite EP: DNA synthesis in circulating blood leukocytes labelled in vitro with H~-thymidine, J Lab Clin Med 58.'751, 196l. Waldmann TA, and McIntire KR: Serum alpha-fetoprotein levels in patients with ataxia-telangiectasia, Lancet 2:1112, 1972. Waldmann TA: In discussion of reference 1 above, p 274.
1. Boder E: Ataxia telangiectasia. Some historic, clinical and pathologic observations, B~rth Defects, 11:255, 1975.
Cutaneous sarcoidosis of childhood David J. Waldman, M.D., and E. Richard Stiehm, M,D,,* Los Angeles, Calif.
SARCOIDOSIS, a noncaseating, g r a n u l o m a t o u s disorder of u n k n o w n origin, is rare in childhood. The most c o m m o n presenting features are constitutional complaints (fever, weight loss, a b d o m i n a l pain, and anorexia) a n d p u l m o n a r y involvement. Skin i n v o l v e m e n t occurs in 30% of cases ~ but is almost invariably associated with o t h e r manifestations of the disease. W e h a v e recently e n c o u n tered a 4-year-old girl whose sole clinical m a n i f e s t a t i o n of sarcoidosis was a m a c u l o p a p u l a r skin rash b e g i n n i n g at the age of 18 months. CASE REPORT Patient C.M. is a 4~/2-year-old Caucasian girl first seen at the UCLA Medical Center in November, 1974, with a chief complaint of a maculopapular nonpruritic skin rash, present on the cheeks, arms buttocks, and thighs since the age of 18 months.
trtvm the Department of Pediatrics, University of CuliJbrnia School of Medicine, Comer for the Health Sciences. ~Ret~rint address: Department of Pediatrics, UCLA Centerjbr the Health Sciences. Los Angeles. CA 90024
The rash appeared gradually over a three-month period and remained unchanged over the next 30 months, except for a complete one-month remission associated with varicella. Because the rash was unresponsive to treatment with topical corticosteroids, a skin biopsy was performed in May, 1974. Because of the presence of a few mast cells in the dermis, a diagnosis of urticaria pigmemosa was considered. On admission, the girl appeared healthy. Weight was 14.8 kg (third percentile): height was 96 cm (third percentile). The physical examination was normal except for an erythematous rash over the malar prominences and the bridge of the nose and a papular rash covering the shoulders, arms, thighs, and buttocks (Fig. 1). Ophthalmic examination was normal. All laboratory determinations were normal or negative including complete blood count, chest and hand roentgenograms, blood chemical values, and B and T cell enumeration, except for a slightly elevated erythrocyte sedimentation rate (28 ram/hour by the Wintrobe method) and an elevated serum lysozyme concentration (13.1 mg/ml, normal 2 to 11 mg/ml). Quantitative serum immunoglobulin levels revealed an IgG of 1,125 mg/dl, IgA 228 mg/dl, IgM 133 mg/dl, and IgE 24 iU/ml. A repeat skin biopsy revealed multiple noncaseating granulomata consistent with sarcoidosis (Fig. 2). A one-month trial of prednisone therapy (1 mg/kg/day) was started and within one week the rash disappeared and within two weeks the erythrocyte sedimentation rate decreased to 12 m m / hour. The rash reappeared one week after discontinuing the prednisone, however, and the erythrocyte sedimentation rate increased to 45 mm/hour over the next five months. In April, 1975, a Kveim test was applied to the forearm; six weeks later a punch biopsy of the site revealed the characteristic noncaseating granulomas of sarcoid. In September, 1975, a routine eye
could be misjudged, if thyroid function is not monitored. For these reasons, children with Turner syndrome should be periodically evaluated for normalcy of their thyroid function. The authors thank MI. G, Henry, Mrs. J. Clark, Ms. N. Lightman, and Mrs. B. Threadgill for technical and secretarial assistance.
REFERENCES I.
Sparkes RS, and Motulsky AB: Hashimoto's disease in Turner's syndrome with isochromosone X, Lancet 1:947, 1963. 2. Williams ED, and Forbes AP: Thyroiditis and gonadal dysgenesis, N Engl J Med 270:805, 1964.
Heat stable E-receptors on leukemic lymphoblasts in ataxiatelangiectasia Eric Cameron, M.D., Rama S. Seshadri, M.D., M.R.A.C.P., K. R. Mohan Pai, M.D., F.R.C.P.(C),
and Peter B. Dent, M.D., F.R.C.P.(C),* Hamilton, Ont,, Canada
A T A X I A - T E L A N G I E C T A S I A is a Complex syndrome; consistent and striking central nervous system degenerative changes occur which are often associated with variable defects in humoral and cellular immunity, x''-' Lymphoreticular and nonlymphoid malignancy are estimated to occur in 10% of the patients? In this report, we describe a 12-year-old boy with ataxia-telangiectasia who developed acute lymphoblastic leukemia in w h o m we have characterized the lymphoblasts as having heat-stable sheep erythrocyte receptors.
CASE REPORT Patient H. V. was diagnosed to have ataxia-telangiectasia at the age of 7 years on the basis of ataxia, conjunctival telangiectases, and frequent respiratory infection. He had no IgA, a low lymphocyte level, negative skin tests, and a depressed PHA *Reprint address: McMaster University Medical Centre, Department of Pediatrics, Room 4H17, 1200 Main Street West, Hamilton, Ont., Canada.
B r i e f clinical and laboratory observations
269
3. Engel E, and Forbes AP: Cytogenetic and clinical findings in 48 patients with congenitally defective or absent ovaries, Medicine 44:135, 1965. 4. Grumbach MM~ and Morishima A:X-chromosome abnormalities in gonadal dysgenesis: DNA replication of structurally abnormal X-chromosomes; relation to thyroid disease, J PEDIATR65:1087, 1964 (abstr). 5. Rallison ML, Debyns BM, Rail JE, and Tyler FH: Occurrence and natural history of chronic lymphocytic thyroiditis in childhood, J PEDIATR86:675, 1975. 6. Leboeuf G, and Ducharme JR: Thyroiditis in children, diagnosis and management, Pediatr Clin North Am 13:19, 1966. 7. Hill OW: Thyroglobulin antibodies in 1,297 patients without thyroid disease, Br Med J 1:1793, 1961.
response. At age 12 he presented with a three-month history of pallor, malaise, fever, and progressive neurologic deterioration. The hemoglobulin concentration was 4.0 gm/dl, WBC 22,700/ mm ~with 99% abnormal mononuclear cells and platelet count of 17,000/ram ~. Peripheral blood smear revealed two populations of abnormal mononuclear cells. One population consisted of small ceils with high nuclear-cytoplasmic ratio and indistinct nucleoli. Some of these small cells showed clefting of the nuclei. Cytoplasm was scant and there were no granules. The second population consisted of large cells with a moderate amount of cytoplasm and an immature nucleus containing one or two distinct nucleoli. The cytoplasm was blue in color and had no granules. The large cell population formed approximately 10% of the abnormal mononuclear cells. Abbreviations used AT: ataxia-telangiectasi a PHA: phytohemagglutinin E: sheep erythrocyte WBC: white blood count Hgb: hemoglobin A bone marrow aspirate showed complete replacement of normal cellular elements by abnormal mononuclear cells similar to those found in the peripheral blood. The morphology of the cells was considered to be atypical for acute lymphoblastic leukemia (Fig. 1). Periodic acid-Schiff stain of the peripheral blood and bone marrow cells revealed no positive reaction. The peroxidase stain was also negative. The results of lymphocyte studies done during the course of the illness are shown in Table I. When first seen in April, 1971, at age 7 years he had a low normal level of peripheral blood lymphocytes with a depressed response to PHA in vitro, using a whole blood microculture technique with optimal and threshold concentrations of mitogen2 At the time of diagnosis of leukemia on April 6, 1976, peripheral blood mononuclear cells were isolated on Ficoll-hypaque gradients and the percentage of cells rosetting with sheep erythrocytes at 0~ and 37~ was deter-
270
Brief clinical and laboratory observations
The Journal of Pediatrics August 1977
Table I. Results of immunologic investigations
Date April 13, 1971 Total lymphocytes (mm~)
1,152
Peripheral blood E- rosettes (%) 0~ ND 37 ~ ND Bone marrow E-rosettes (%) 0~ ND 37 ~ Lymphocyte stimulation (cpm :'H-thymidine incorporation) PHA l0 ~tg/ml 1,028 ( > 10,000) PHA 0.3/~g/ml 1,414 ( > 2,000) Unstimulated 52 ( < 200)
April 6, 1976 22,000 abnormal mononuclear
[
April 27, 1976
I
June 6, 1976
7,968
133
80 (63)* 70 (16)
20 (63) 1 (1)
ND ND
88 75
ND
ND
4,333 4,469 4,004
28,186 1,220 425
81 55 31
*Figures in brackets represent normal adult controls.
and 6-mercaptopurine (50 mg/m2/week) but the patient developed pneumonia unresponsive to antibiotics about two weeks later. On June 6, 1976, four weeks after the start of the maintenance schedule the complete blood count was as follows: Hgb 6.2 gm/dl; platelets 70,000/mm~; WBC 1,900/mm a with 83% neutrophils, 9% band forms, 2.% eosinophils, and 7% lymphocytes. There was a marked suppression of his lymphocyte stimulation response (Table I). The patient died 11 weeks aft.er the initial diagnosis of acute lymphoblastic leukemia. At autopsy the thymus and lymphoid tissues were hypoplastic and dysplastic, lntranuclear inclusion bodies were present in numerous organs compatible with widespread cytomegalovirus infection. FiR. 1. Bone marrow aspirate showing the two morphologic types of abnormal lymphoid cells: the predominant small cell with high nu~zlear cytoplasmic ratio and the larger cell with more abundant cytoplasm and immature nucleus (magnification 800 x ). mined? Seventy percent (70%) formed heat stable rosettes as compared with 16% of cells from a normal control individual. Seventy-five percent (75%) of the bone marrow mononuclear cells isolated in a similar fashion formed heat stable E rosettes. In vitro lymphocyte cultures showed a high unstimulated value of 3H-thymidine uptake compatible with large numbers of rapidly dividing cells in the peripheral blood. ~ There was no increase in :'H-thymidine uptake in cultures containing PHA. He was treated with vincristine (l.5 mg/m ~ weekly) and prednisone (50 mg/m ~ daily). On April 27, 1976, three weeks after the start of chemotherapy h e was in remission as judged by peripheral blood smear. Complete Nodd count revealed: Hgb 12.4 gm/dl; WBC 16,600/mm ~ with 5% myelocytes, 3% metamyelocytes, 15% band forms, 63% neutrophils, 45% lymphocytes, and 4% monocytes. Platelet count was 369 000/mm ~. A repeat of the lymphocyt e stimulation showed a normal response to optimal concentration of PHA. Repeat E-rosette studies showed 20% at 0 ~ and 0% at 37~ Therapy was maintained with m ethotrexate (20 mg/mVweek)
COMMENT The precise nature of the defect in AT is poorly understood. The abnormality is clearly not limited to the lymphoid system but appears to be a fundamental defect in cellular differentiation affecting thymus, central nervous system, blood vessels, and gonadsF The finding of elevated levels of alpha fetoprotein in patients with A T is consistent with this hypothesis. 7 In our patient both alpha fetoprotein and the carcinoembryonic antigen* levels were e l e v a t e d - 4 0 0 n g / m l and 10.7 ng/ml, respectively. These patients' susceptibility to neoplasia is well known and may relate as much to the fundamental defect as to the associated imraunodeficiency. The uniqueness of this report is the finding of receptors for sheep erythrocytes on the a b n o r m a l cells in blood and bone marrow, which permit the further definition of the neoplasia as a T cell leukemia. The heat stability of the rosetting lymphocytes differentiates these cells from mature peripheral blood T cells? This temperature independence has been shown to be characteristic of undifferentiated normal T cells within the thymus as well as
Volume 91 Number 2
Brief cfinical and laboratory observations
leukemic l y m p h o b l a s t s o f the T cell variety? It is o f interest that as the patient went into remission the blood m o n o n u c l e a r cell E-rosettes [ost their heat stability a n d showed i m p r o v e d responsiveness to P H A indicating a disappearance o f the a b n o r m a l lymphoblasts, The designation of the leukemia in our patient as T cell in nature is of interest because of the previously described functional a n d morpholog~c thymic a b n o r m a l i t i e s in ataxia-telangiectasia. As indicated above the pathogenesis of the thymic a b n o r m a l i t i e s is not k n o w n a l t h o u g h it has been postulated that a defect in the thymic e p i t h e l i u m m a y be responsible for the a b n o r m a l l y m p h o c y t e function. It is interesting to speculate that the h e i g h t e n e d susceptibility of A T lymphocytes to neoplastic transform a t i o n m a y be secondary to the chronic inability o f the T cells to undergo complete m a t u r a t i o n .
2.
REFERENCES
8.
3.
4.
5.
6.
7.
271
Peterson RDA, Cooper MD, and Good RA: Lymphoid tissue abnormalities associated with ataxia-telangiectasia, Am J Med 41:342, 1966. Kersey JH, Spector BD, and Good RA: Primary immunodeficiency diseases and cancer: The immunodeficiencycancer registry, lnt J Cancer 12:333, 1973. Lui VK, Karpuchas J, Dent PB, McCulloch PB, and Blajchman MA: Cellular immunocompetence in melanoma: Effect of extent of disease and immunotherapy, Br J Cancer 32:323, 1975. Borella L, and Sen L: E receptors on blasts from untreated acute lymphocytic leukemia: Comparison of temperature dependence of E rosettes formed by normal and leukemic lymphoid cells, J Immunol 114:187, 1975. Rubini JR, Bond VP, Keller S, Fliedner TM, and Cronkite EP: DNA synthesis in circulating blood leukocytes labelled in vitro with H~-thymidine, J Lab Clin Med 58.'751, 196l. Waldmann TA, and McIntire KR: Serum alpha-fetoprotein levels in patients with ataxia-telangiectasia, Lancet 2:1112, 1972. Waldmann TA: In discussion of reference 1 above, p 274.
1. Boder E: Ataxia telangiectasia. Some historic, clinical and pathologic observations, B~rth Defects, 11:255, 1975.
Cutaneous sarcoidosis of childhood David J. Waldman, M.D., and E. Richard Stiehm, M,D,,* Los Angeles, Calif.
SARCOIDOSIS, a noncaseating, g r a n u l o m a t o u s disorder of u n k n o w n origin, is rare in childhood. The most c o m m o n presenting features are constitutional complaints (fever, weight loss, a b d o m i n a l pain, and anorexia) a n d p u l m o n a r y involvement. Skin i n v o l v e m e n t occurs in 30% of cases ~ but is almost invariably associated with o t h e r manifestations of the disease. W e h a v e recently e n c o u n tered a 4-year-old girl whose sole clinical m a n i f e s t a t i o n of sarcoidosis was a m a c u l o p a p u l a r skin rash b e g i n n i n g at the age of 18 months. CASE REPORT Patient C.M. is a 4~/2-year-old Caucasian girl first seen at the UCLA Medical Center in November, 1974, with a chief complaint of a maculopapular nonpruritic skin rash, present on the cheeks, arms buttocks, and thighs since the age of 18 months.
trtvm the Department of Pediatrics, University of CuliJbrnia School of Medicine, Comer for the Health Sciences. ~Ret~rint address: Department of Pediatrics, UCLA Centerjbr the Health Sciences. Los Angeles. CA 90024
The rash appeared gradually over a three-month period and remained unchanged over the next 30 months, except for a complete one-month remission associated with varicella. Because the rash was unresponsive to treatment with topical corticosteroids, a skin biopsy was performed in May, 1974. Because of the presence of a few mast cells in the dermis, a diagnosis of urticaria pigmemosa was considered. On admission, the girl appeared healthy. Weight was 14.8 kg (third percentile): height was 96 cm (third percentile). The physical examination was normal except for an erythematous rash over the malar prominences and the bridge of the nose and a papular rash covering the shoulders, arms, thighs, and buttocks (Fig. 1). Ophthalmic examination was normal. All laboratory determinations were normal or negative including complete blood count, chest and hand roentgenograms, blood chemical values, and B and T cell enumeration, except for a slightly elevated erythrocyte sedimentation rate (28 ram/hour by the Wintrobe method) and an elevated serum lysozyme concentration (13.1 mg/ml, normal 2 to 11 mg/ml). Quantitative serum immunoglobulin levels revealed an IgG of 1,125 mg/dl, IgA 228 mg/dl, IgM 133 mg/dl, and IgE 24 iU/ml. A repeat skin biopsy revealed multiple noncaseating granulomata consistent with sarcoidosis (Fig. 2). A one-month trial of prednisone therapy (1 mg/kg/day) was started and within one week the rash disappeared and within two weeks the erythrocyte sedimentation rate decreased to 12 m m / hour. The rash reappeared one week after discontinuing the prednisone, however, and the erythrocyte sedimentation rate increased to 45 mm/hour over the next five months. In April, 1975, a Kveim test was applied to the forearm; six weeks later a punch biopsy of the site revealed the characteristic noncaseating granulomas of sarcoid. In September, 1975, a routine eye