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Hypogammaglobulinemia and antibody deficiency in patients with elevated sweat chloride concentrations
420
Brief clinical and laboratory observations
6. Wilkinson JD, Dawber RPR, Bowers RP, and Fleming K: Twenty-nail dystrophy of childhood, Br J Dermatol 100:217, 1979. 7. Samman PD: Trachyonychia (rough nails), Br J Dermatol 101:701, 1979. 8. Horn RT, and Odom RB: Twenty-nail dystrophy of alopecia areata, Arch Dermatol 116:573, 1980. 9. Taaffe A: Current concepts in lichen planus, lnt J Dermatol 18:533, t979. 10. Herzer P, Czarnetzki BM, Hotzmann H, and Lemmel EM:
The Journal o f Pediatrics March 1982
Immunological studies in patients with alopecia areata, Int Arch Allergy Appl lmmunol 58:212, 1979. 11. Happle R: Antigenic competition as a therapeutic concept for alopecia areata, Arch Dermatol Res 267:109, 1980. 12. Wahba A: Immunological alterations in psoriasis, lnt J Dermatol 19:124, 1980. 13. Ammann A J, and Hong R: Disorders of the lgA System, in Stiehm ER, and Fulginiti VA, editors: Immunological disorders in infants and children, ed 2, Philadelphia, 1980, WB Saunders Company.
Hypogammaglobulinemia and antibody deficiency in patients with elevated sweat chloride concentrations Christopher W. B. Corkey, M,B., and Erwin W. Gelfand, M.D.,* Toronto, Ont, Canada
OCCASIONALLY, an elevated sweat chloride c o n c e n t r a tion has been associated with conditions other t h a n cystic fibrosis.l. 2 It is unlikely, however, that t h e s e conditions will be c o n f u s e d clinically with cystic fibrosis. M a t t h e w s et aP have recently s h o w n t h a t 22% of children with cystic fibrosis u n d e r 10 years of age have low c o n c e n t r a t i o n s o f IgG: H o w e v e r , t h e s e subjects were shown to have n o r m a l a n t i b o d y responses to p a r e n t e r a l l y a d m i n i s t e r e d antigens. In this c o m m u n i c a t i o n , we r e p o r t t h r e e patients w h o were investigated b e c a u s e o f elevated sweat chloride values a n d c h r o n i c respiratory infection in w h o m a diagnosis o f a n t i b o d y deficiency r a t h e r t h a n C F could be m a d e . CASE REPORTS Patient 1. This 24-year-old male Caucasian was first seen at 12 years of age following admission for investigation of growth retardation. There was a history of about three hospital admissions with pneumonia and bronchitis per year during the preschool years, and subsequently one per year. A three-year history of rash over the face and extensor surfaces of both knees and elbows was also elicited. He had a normal diet and no gastrointestinal symptoms. Physical examination was unremarkable except for some roughened erythematous areas over the face, and height and weight were below the third percentile. The patient had a productive cough with copious amounts of green sputum. Chest radiographs showed left lower lobe atelectasis; sinus radiographs showed pansinusitis. Laboratory investigations included a hemoglobin of 12 gm/dl, WBC count 5,500/mm 3 with a normal
From the Division of Immunology, The Hospital for Sick Children. K *Reprints address Division of Immunology, Hospital for Sick Children, 555 University Ave., Toronto, Ont., Canada, M5G IX8.
differential. Sputum culture yielded a scanty growth of Pseudomonas aeruginosa and Serratia marcescens. Sweat chloride concentrations (urecholine iontophoresis) were high on three occasions, being 62, 73, and 85 mEq/L, respectively. Fat excretion was not elevated. Stool trypsin and chymotrypsin values were within normal limits. Serum immunoglobulin assays were done on several occasions; IgG was always low, the highest value being 250 mg/dl; IgA was always 0; and lgM was consistently low, the highest value being 16 mg/dl. There was no evidence of abnormality of thyroid, pituitary, or adrenal function. The skin lesion was diagnosed following skin biopsy as atrophia maculosa varioliformis cutis. He was started on a routine regimen of physiotherapy and continuous antibiotic therapy and initially made some improvement. At the age of 13 years, he was reassessed in view of deterioration of his chest condition, with increased atelectasis of the left lower lobe. Sweat chloride determinations were repeated on five occasions and were normal, ranging between 37 to 47 mEq/L. At 19 years of age, the sweat chloride concentration was 53 mEq/L. Normal quantities of pancreatic enzymes were demonstrated following pancreatic stimulation tests. Immunoglobulins were again shown to be low and the isohemagglutinin titer (anti-B) was 1:2. Schick test was positive and there was no antibody response to polio or tetanus antigens, even following a booster immunization. Bone marrow aspiration showed no plasma cells. He was subsequently treated with gammaglobulin and made a gradual but slow improvement, with no further episodes of pneumonia. Patient 2. This 1&year-old male Caucasian was investigated at the age of 10 years because of a history of recurrent pharyngitis and frequent courses of antibiotic therapy. He also had recurrent otiiis media and had myringotomies on two occasions. In addition, he had a history of pneumonia at 2 and at 4 years of age, At the age of 8 years, he developed eczema. He had received the usual immunizations with DPT, polio, and, smallpox vaccines, and had contracted rubella, rubeola, and chickenpox before 7 years of age with no complications. Investigations revealed a low gammaglobu-
0022-3476/82/030420+03500.30/0 9 1982 The C. V. Mosby Co.
Volume 100 Number 3 lin fraction on electrophoresis (0.3 gm/L). Quantitive immunoglobulin concentrations were IgG 380 mg/dl, IgA 0, lgM < 20 mg/dl. A Schick test was negative. Lymph node biopsy showed an absence of follicle formation and no plasma cells. Isohemagglutinin titers were lov~ (1:1 to 1:2) and he failed to mount an appropriate antibody response to polio and tetanus reimmunization. He was treated with parenteral replacement of gammaglobulin. Soon thereafter, he develoPed right middle lobe and lingular atelectasis, which failed to improve with intensive physiotherapy and appropriate antibiotic therapy. Bronchoscopy revealed purulent thin liquid secretions from both affected regions. During this admission, sweat Chloride assessments were performed on three occasions and were found to be 81, 84, and 96 mEq/L, respectively (urecholine iontophoresis). Fecal fat excretion was not elevated. Chest radiograph showed none of the features typically associated with cystic fibrosis. The patient has subsequently been maintained on gammaglobulin therapy and has had an improvement, both in the appearance of the chest radiograph and in pulmonary function test values. Patient 3. This 14-year-old female Caucasian had a history of recurrent respiratory tract infections with cough, wheezing, and purulent sputum production from age 4 years, especially in the winter; this was diagnose d as bronchitis. In addition, she had focal sclerosing glomerulonephritis, diagnosed at the age of 4 years by renal biopsy. She was treated with prednisone and cyclophosphamide, the latter being discontinued after six .months and prednisone discontinued at the age of 12 years. At 9 years of age, She was noted to have vitiligo on the elbows, knees, ankles, and eyebrows9 At 13 years of age, she had an episode of pneumonia in the left lower lobe. Six months later, she developed bilateral pneumonia; investigations at this time included sweat chloride assessment, which was elevated at '61 mEq/L on one occasion. Subsequent sweat chloride values were normal (25 and 27 mEq/L), lmmunoelectrophoresis showed low gammaglobuli n values and quantitive immunoglobulin concentrations were lgG 42 mg/dl, IgA < 5 mg/dl, and lgM < 8 mg/dl. Is0hemagglutinins were not detectable and she failed to mount appropriate antibody responses following booster immunization. Gammaglobulin therapy was subsequently started and she has remained well since that time, with sweat chloride concentrations remaining within the normal range. DISCUSSION Cystic fibrosis is suspected on the basis of a history of recurrent pulmonary disease, pancreatic insufficiency, or a family history of the diseas e . Confirmation of the diagnosis is made by the finding of an elevated sweat chloride concentration with or without the demonstration of pancreatic insufficiency2 Sweat chloride evaluation Should be repeated on two or preferably three occasions, a number of months apart; a single elevated sweat chloride value should not be considered diagnostic of the condition. The diagnosis of cystic fibrosis was dismissed in one of our patients (Patient 3), despite the initial finding of a raised sweat chloride concentration, by the subsequent finding of two normal values. However, as noted previously, a number of
Brief clinical and laboratory observations
421
conditions are associated with raised sweat chloride values. 2 None of these is associated with a clinical picture which is likely to be mistaken for cystic fibrosis. On the other hand, although hypogammaglobulinemia may present with generalized infection of many organs, recurrent infections are often restricted to the respiratory system, as was seen in each of our patients. 4 The initial diagnostic evaluation for a patient suspected of having cystic fibrosis should include an assessment of serum immunoglobulins; the need for this assessment is further emphasized by the finding of elevated sweat chloride values in our three patients. It is generally accepted that the serum immunoglobulin concentrations in patients with cystic fibrosis rise progressively both with age and increasing infection? ,6 However, Matthews et aP recently have assessed the immunoglobulin values in patients with cystic fibrosis in relation to clinical status, and have shown that 22% of 153 patients with cystic fibrosis of 10 years or less had low serum IgG concentrations (serum IgA and IgM values, although lower in patients with cystic fibrosis with normal or elevated IgG, were within the normal range). Rather than having more severe clinical problems, these patients had less serious lung disease with respect to radiologic changes, reduced colonization with Pseudomonas aeruginosa, and higher Pao2 values compared to age-matched controls with the disease who had normal or elevated serum immunoglobulin values. The finding of hypogammaglobulinemia per se, however, does not indicate a specific dysfunction in antibody production, and each of eight subjects in the group studied by Matthews et al had a normal antibody response to parenterally administered tetanus antigen. Consequently, if low serum immunoglobulin concentrations are found in a patient being investigated for possible cystic fibrosis, immunoelectrophoresis and tests of specific antibody production should be performed to exclude hypogammaglobulinemia as an etiologic factor. The institution of the typical cystic fibrosis treatment regimen of intensive physiotherapy and either continuous prophylactic or intermittent antibiotic therapy will, in general, produce a significant clinical improvement in a patient with either cystic fibrosis or hypogammaglobulinemia. However, the addition of gammaglobulin replacement therapy is required in hypogammaglobulinemia to prevent further deterioration in pulmonary function, although progressive lung disease may occur despite therapy. v In summary, studies of specific antibody formation should be carried out in patients with elevated sweat chloride values and hypogammaglobulinemia. Conversely, the finding of elevated sweat chloride concentrations in patients with repeated lung infections is not sufficient
422
Brief clinical and laboratory observations
The Journal of Pediatrics March 1982
alone to make a diagnosis of cystic fibrosis or to eliminate consideration of an underlying immune deficiency.
3.
We are indebted to Drs. D. Crozier and H. Levison for referral of their patients to us.
4.
REFERENCES
1. Di Sant-Agnese PA, and Talamo RC: Pathogenesis and physiopathology of cystic fibrosis of the pancreas. Fibrocystic disease of the pancreas (mucoviscidosis), N Eng! J Med 277:1344, 1967. 2. Wood RE, Boat TE, and Doershuk CF: Cystic fibrosis, Am Rev Respir Dis 113:833, 1976.
5.
6. 7.
Matthews WJ Jr, Williams M, Oliphant B, Geha R, and Colten HR: Hyp0gammaglobulinemia in patients with cystic fibrosis, N Engl J Med 302:245, 1980. Dauber JH, and Fogarty CM: Immune-deficiency states and recurrent respiratory tract infections, in Fishman AP, editor: Pulmonary diseases and disorders, vol 2, New York, 1980. McGraw-Hill Book Company, pp 997. Green MN, Kulczycki LL, and Shwachman H: Serum protein paper electrophoresis in patients with cystic fibrosis, Am J Dis Child 100:365, 1960. Schwartz RH: Serum immunoglobulin levels in cystic fibrosis, Am J Dis Child 111:408, 1966. Phelan PD, Landau LI, and Williams HE: Lung disease associated with infantile agammaglobulinemia, Aust Paediatr J 9i147, 1973.
Leukemic involvement of the ovaries in childhood acute lymphocytic leukemia Salem O. Zarrouk, M.D., Tae H. Kim, M.D., Hilary K, Hargreaves, M.D., and Abdelsalam H. Ragab, M.D.,* Atlanta, Ga.
As CrlILDRBN with acute lYmphocytic leukem!a survive longer, leukemic involvement of the testes is being recognized more frequently 1-3 and testicular biopsy, even in asymptomatic patients, is being performed on a routine basis. '-5 However, leukemic involvement of the ovaries has received little attention, and the significance of ovarian-associated relapse in relation to the eventual outcome of the patient has not been investigated. We describe two female patients with A L L who completed three years o f chemotherapy. Both developed ovarian-related relapses after cessation of therapy. CASE REPORTS Patien t 1. This 4-year-old white girl was diagnosed as having ALL in August, 1976, when she presented with anemia, thrombocytopenia, and hepatomegaly. Remission was successfully induced with vincristine and prednisone therapy. She received CNS prophylaxis with serial intrathecal injections of methotrexate, and was maintained on 6-mercaptopurine and methotrexate
From the Division of Pediatric Hematology/Oncology, Department of Pediatrics and Department of Pathology and Laboratory Medicine, Emory University School of Medicine. Supported by the CURE organization of Georgia and National Institutes of Healt h Grant Nol 1 RIO CA20549 and Teaching Grant CA17998. Dr. Ragab is the recipient of a faculty research awarc~ from the American Cancer Society. *Reprint address: Department of Pediatrics, 1365 Clifton Road, NE, Atlanta, GA 30322.
therapy for three years. A complete physical examination, lumbar puncture, and bone marrow study iat the time of cessation of chemotherapy showed no evidence of leukemia. Bone marrow aspil"ations were then performed every eight weeks. Eight months after chemotherapy was discontinued, she developed hematuria.
Abbreviations used ALL: acute lymphocytic leukemia IVP: intravenous pyelogram CNS: central nervous system
On physical examination, a large pelvic mass was found. An IVP showed marked hydronephrosis and hydroureter on the right side, with a large soft tissue mass filling the pelvis. At laparotomy there were diffusely enlarged and matted para-aortic lymph nodes, and a large solid pelvic mass which involved both ovaries, uterus, and iliac nodes. Biopsy of the pelvic mass demonstrated that it was composed of lymphoblasts (Figure). A bone marrow aspiration at this time showed 34% lymPhoblasts (n-T, non-B type). The patien t then received the modified LSA~-L2protocol. T No abdominal irradiation was given. Six months following the ovarian relapse the patient is disease free and continues to receive the LSA2-L2 maintenance regimen. Patient 2. This 2a/2-year-old white girl was seen at Emory University clinic in April, 1977, when she was found to have anemia and thrombocytopenia. Physical examination showed no 0rganomegaly or lymphadenopathy. The hemoglobin was 6.8 gm/d!, WBC 22,500/mm *, and plate!et count 26,000/mm 3. A bone marrow aspiration was diagnostic of ALL of non-T, non-B type, and remission was induced with vincristine, prednisone, and L'asparaginase therapy. After completion of CNS pr0phylax0022-3476/82/030422+03500.30/0 9 1982 The C. V. Mosby Co.
Brief clinical and laboratory observations
6. Wilkinson JD, Dawber RPR, Bowers RP, and Fleming K: Twenty-nail dystrophy of childhood, Br J Dermatol 100:217, 1979. 7. Samman PD: Trachyonychia (rough nails), Br J Dermatol 101:701, 1979. 8. Horn RT, and Odom RB: Twenty-nail dystrophy of alopecia areata, Arch Dermatol 116:573, 1980. 9. Taaffe A: Current concepts in lichen planus, lnt J Dermatol 18:533, t979. 10. Herzer P, Czarnetzki BM, Hotzmann H, and Lemmel EM:
The Journal o f Pediatrics March 1982
Immunological studies in patients with alopecia areata, Int Arch Allergy Appl lmmunol 58:212, 1979. 11. Happle R: Antigenic competition as a therapeutic concept for alopecia areata, Arch Dermatol Res 267:109, 1980. 12. Wahba A: Immunological alterations in psoriasis, lnt J Dermatol 19:124, 1980. 13. Ammann A J, and Hong R: Disorders of the lgA System, in Stiehm ER, and Fulginiti VA, editors: Immunological disorders in infants and children, ed 2, Philadelphia, 1980, WB Saunders Company.
Hypogammaglobulinemia and antibody deficiency in patients with elevated sweat chloride concentrations Christopher W. B. Corkey, M,B., and Erwin W. Gelfand, M.D.,* Toronto, Ont, Canada
OCCASIONALLY, an elevated sweat chloride c o n c e n t r a tion has been associated with conditions other t h a n cystic fibrosis.l. 2 It is unlikely, however, that t h e s e conditions will be c o n f u s e d clinically with cystic fibrosis. M a t t h e w s et aP have recently s h o w n t h a t 22% of children with cystic fibrosis u n d e r 10 years of age have low c o n c e n t r a t i o n s o f IgG: H o w e v e r , t h e s e subjects were shown to have n o r m a l a n t i b o d y responses to p a r e n t e r a l l y a d m i n i s t e r e d antigens. In this c o m m u n i c a t i o n , we r e p o r t t h r e e patients w h o were investigated b e c a u s e o f elevated sweat chloride values a n d c h r o n i c respiratory infection in w h o m a diagnosis o f a n t i b o d y deficiency r a t h e r t h a n C F could be m a d e . CASE REPORTS Patient 1. This 24-year-old male Caucasian was first seen at 12 years of age following admission for investigation of growth retardation. There was a history of about three hospital admissions with pneumonia and bronchitis per year during the preschool years, and subsequently one per year. A three-year history of rash over the face and extensor surfaces of both knees and elbows was also elicited. He had a normal diet and no gastrointestinal symptoms. Physical examination was unremarkable except for some roughened erythematous areas over the face, and height and weight were below the third percentile. The patient had a productive cough with copious amounts of green sputum. Chest radiographs showed left lower lobe atelectasis; sinus radiographs showed pansinusitis. Laboratory investigations included a hemoglobin of 12 gm/dl, WBC count 5,500/mm 3 with a normal
From the Division of Immunology, The Hospital for Sick Children. K *Reprints address Division of Immunology, Hospital for Sick Children, 555 University Ave., Toronto, Ont., Canada, M5G IX8.
differential. Sputum culture yielded a scanty growth of Pseudomonas aeruginosa and Serratia marcescens. Sweat chloride concentrations (urecholine iontophoresis) were high on three occasions, being 62, 73, and 85 mEq/L, respectively. Fat excretion was not elevated. Stool trypsin and chymotrypsin values were within normal limits. Serum immunoglobulin assays were done on several occasions; IgG was always low, the highest value being 250 mg/dl; IgA was always 0; and lgM was consistently low, the highest value being 16 mg/dl. There was no evidence of abnormality of thyroid, pituitary, or adrenal function. The skin lesion was diagnosed following skin biopsy as atrophia maculosa varioliformis cutis. He was started on a routine regimen of physiotherapy and continuous antibiotic therapy and initially made some improvement. At the age of 13 years, he was reassessed in view of deterioration of his chest condition, with increased atelectasis of the left lower lobe. Sweat chloride determinations were repeated on five occasions and were normal, ranging between 37 to 47 mEq/L. At 19 years of age, the sweat chloride concentration was 53 mEq/L. Normal quantities of pancreatic enzymes were demonstrated following pancreatic stimulation tests. Immunoglobulins were again shown to be low and the isohemagglutinin titer (anti-B) was 1:2. Schick test was positive and there was no antibody response to polio or tetanus antigens, even following a booster immunization. Bone marrow aspiration showed no plasma cells. He was subsequently treated with gammaglobulin and made a gradual but slow improvement, with no further episodes of pneumonia. Patient 2. This 1&year-old male Caucasian was investigated at the age of 10 years because of a history of recurrent pharyngitis and frequent courses of antibiotic therapy. He also had recurrent otiiis media and had myringotomies on two occasions. In addition, he had a history of pneumonia at 2 and at 4 years of age, At the age of 8 years, he developed eczema. He had received the usual immunizations with DPT, polio, and, smallpox vaccines, and had contracted rubella, rubeola, and chickenpox before 7 years of age with no complications. Investigations revealed a low gammaglobu-
0022-3476/82/030420+03500.30/0 9 1982 The C. V. Mosby Co.
Volume 100 Number 3 lin fraction on electrophoresis (0.3 gm/L). Quantitive immunoglobulin concentrations were IgG 380 mg/dl, IgA 0, lgM < 20 mg/dl. A Schick test was negative. Lymph node biopsy showed an absence of follicle formation and no plasma cells. Isohemagglutinin titers were lov~ (1:1 to 1:2) and he failed to mount an appropriate antibody response to polio and tetanus reimmunization. He was treated with parenteral replacement of gammaglobulin. Soon thereafter, he develoPed right middle lobe and lingular atelectasis, which failed to improve with intensive physiotherapy and appropriate antibiotic therapy. Bronchoscopy revealed purulent thin liquid secretions from both affected regions. During this admission, sweat Chloride assessments were performed on three occasions and were found to be 81, 84, and 96 mEq/L, respectively (urecholine iontophoresis). Fecal fat excretion was not elevated. Chest radiograph showed none of the features typically associated with cystic fibrosis. The patient has subsequently been maintained on gammaglobulin therapy and has had an improvement, both in the appearance of the chest radiograph and in pulmonary function test values. Patient 3. This 14-year-old female Caucasian had a history of recurrent respiratory tract infections with cough, wheezing, and purulent sputum production from age 4 years, especially in the winter; this was diagnose d as bronchitis. In addition, she had focal sclerosing glomerulonephritis, diagnosed at the age of 4 years by renal biopsy. She was treated with prednisone and cyclophosphamide, the latter being discontinued after six .months and prednisone discontinued at the age of 12 years. At 9 years of age, She was noted to have vitiligo on the elbows, knees, ankles, and eyebrows9 At 13 years of age, she had an episode of pneumonia in the left lower lobe. Six months later, she developed bilateral pneumonia; investigations at this time included sweat chloride assessment, which was elevated at '61 mEq/L on one occasion. Subsequent sweat chloride values were normal (25 and 27 mEq/L), lmmunoelectrophoresis showed low gammaglobuli n values and quantitive immunoglobulin concentrations were lgG 42 mg/dl, IgA < 5 mg/dl, and lgM < 8 mg/dl. Is0hemagglutinins were not detectable and she failed to mount appropriate antibody responses following booster immunization. Gammaglobulin therapy was subsequently started and she has remained well since that time, with sweat chloride concentrations remaining within the normal range. DISCUSSION Cystic fibrosis is suspected on the basis of a history of recurrent pulmonary disease, pancreatic insufficiency, or a family history of the diseas e . Confirmation of the diagnosis is made by the finding of an elevated sweat chloride concentration with or without the demonstration of pancreatic insufficiency2 Sweat chloride evaluation Should be repeated on two or preferably three occasions, a number of months apart; a single elevated sweat chloride value should not be considered diagnostic of the condition. The diagnosis of cystic fibrosis was dismissed in one of our patients (Patient 3), despite the initial finding of a raised sweat chloride concentration, by the subsequent finding of two normal values. However, as noted previously, a number of
Brief clinical and laboratory observations
421
conditions are associated with raised sweat chloride values. 2 None of these is associated with a clinical picture which is likely to be mistaken for cystic fibrosis. On the other hand, although hypogammaglobulinemia may present with generalized infection of many organs, recurrent infections are often restricted to the respiratory system, as was seen in each of our patients. 4 The initial diagnostic evaluation for a patient suspected of having cystic fibrosis should include an assessment of serum immunoglobulins; the need for this assessment is further emphasized by the finding of elevated sweat chloride values in our three patients. It is generally accepted that the serum immunoglobulin concentrations in patients with cystic fibrosis rise progressively both with age and increasing infection? ,6 However, Matthews et aP recently have assessed the immunoglobulin values in patients with cystic fibrosis in relation to clinical status, and have shown that 22% of 153 patients with cystic fibrosis of 10 years or less had low serum IgG concentrations (serum IgA and IgM values, although lower in patients with cystic fibrosis with normal or elevated IgG, were within the normal range). Rather than having more severe clinical problems, these patients had less serious lung disease with respect to radiologic changes, reduced colonization with Pseudomonas aeruginosa, and higher Pao2 values compared to age-matched controls with the disease who had normal or elevated serum immunoglobulin values. The finding of hypogammaglobulinemia per se, however, does not indicate a specific dysfunction in antibody production, and each of eight subjects in the group studied by Matthews et al had a normal antibody response to parenterally administered tetanus antigen. Consequently, if low serum immunoglobulin concentrations are found in a patient being investigated for possible cystic fibrosis, immunoelectrophoresis and tests of specific antibody production should be performed to exclude hypogammaglobulinemia as an etiologic factor. The institution of the typical cystic fibrosis treatment regimen of intensive physiotherapy and either continuous prophylactic or intermittent antibiotic therapy will, in general, produce a significant clinical improvement in a patient with either cystic fibrosis or hypogammaglobulinemia. However, the addition of gammaglobulin replacement therapy is required in hypogammaglobulinemia to prevent further deterioration in pulmonary function, although progressive lung disease may occur despite therapy. v In summary, studies of specific antibody formation should be carried out in patients with elevated sweat chloride values and hypogammaglobulinemia. Conversely, the finding of elevated sweat chloride concentrations in patients with repeated lung infections is not sufficient
422
Brief clinical and laboratory observations
The Journal of Pediatrics March 1982
alone to make a diagnosis of cystic fibrosis or to eliminate consideration of an underlying immune deficiency.
3.
We are indebted to Drs. D. Crozier and H. Levison for referral of their patients to us.
4.
REFERENCES
1. Di Sant-Agnese PA, and Talamo RC: Pathogenesis and physiopathology of cystic fibrosis of the pancreas. Fibrocystic disease of the pancreas (mucoviscidosis), N Eng! J Med 277:1344, 1967. 2. Wood RE, Boat TE, and Doershuk CF: Cystic fibrosis, Am Rev Respir Dis 113:833, 1976.
5.
6. 7.
Matthews WJ Jr, Williams M, Oliphant B, Geha R, and Colten HR: Hyp0gammaglobulinemia in patients with cystic fibrosis, N Engl J Med 302:245, 1980. Dauber JH, and Fogarty CM: Immune-deficiency states and recurrent respiratory tract infections, in Fishman AP, editor: Pulmonary diseases and disorders, vol 2, New York, 1980. McGraw-Hill Book Company, pp 997. Green MN, Kulczycki LL, and Shwachman H: Serum protein paper electrophoresis in patients with cystic fibrosis, Am J Dis Child 100:365, 1960. Schwartz RH: Serum immunoglobulin levels in cystic fibrosis, Am J Dis Child 111:408, 1966. Phelan PD, Landau LI, and Williams HE: Lung disease associated with infantile agammaglobulinemia, Aust Paediatr J 9i147, 1973.
Leukemic involvement of the ovaries in childhood acute lymphocytic leukemia Salem O. Zarrouk, M.D., Tae H. Kim, M.D., Hilary K, Hargreaves, M.D., and Abdelsalam H. Ragab, M.D.,* Atlanta, Ga.
As CrlILDRBN with acute lYmphocytic leukem!a survive longer, leukemic involvement of the testes is being recognized more frequently 1-3 and testicular biopsy, even in asymptomatic patients, is being performed on a routine basis. '-5 However, leukemic involvement of the ovaries has received little attention, and the significance of ovarian-associated relapse in relation to the eventual outcome of the patient has not been investigated. We describe two female patients with A L L who completed three years o f chemotherapy. Both developed ovarian-related relapses after cessation of therapy. CASE REPORTS Patien t 1. This 4-year-old white girl was diagnosed as having ALL in August, 1976, when she presented with anemia, thrombocytopenia, and hepatomegaly. Remission was successfully induced with vincristine and prednisone therapy. She received CNS prophylaxis with serial intrathecal injections of methotrexate, and was maintained on 6-mercaptopurine and methotrexate
From the Division of Pediatric Hematology/Oncology, Department of Pediatrics and Department of Pathology and Laboratory Medicine, Emory University School of Medicine. Supported by the CURE organization of Georgia and National Institutes of Healt h Grant Nol 1 RIO CA20549 and Teaching Grant CA17998. Dr. Ragab is the recipient of a faculty research awarc~ from the American Cancer Society. *Reprint address: Department of Pediatrics, 1365 Clifton Road, NE, Atlanta, GA 30322.
therapy for three years. A complete physical examination, lumbar puncture, and bone marrow study iat the time of cessation of chemotherapy showed no evidence of leukemia. Bone marrow aspil"ations were then performed every eight weeks. Eight months after chemotherapy was discontinued, she developed hematuria.
Abbreviations used ALL: acute lymphocytic leukemia IVP: intravenous pyelogram CNS: central nervous system
On physical examination, a large pelvic mass was found. An IVP showed marked hydronephrosis and hydroureter on the right side, with a large soft tissue mass filling the pelvis. At laparotomy there were diffusely enlarged and matted para-aortic lymph nodes, and a large solid pelvic mass which involved both ovaries, uterus, and iliac nodes. Biopsy of the pelvic mass demonstrated that it was composed of lymphoblasts (Figure). A bone marrow aspiration at this time showed 34% lymPhoblasts (n-T, non-B type). The patien t then received the modified LSA~-L2protocol. T No abdominal irradiation was given. Six months following the ovarian relapse the patient is disease free and continues to receive the LSA2-L2 maintenance regimen. Patient 2. This 2a/2-year-old white girl was seen at Emory University clinic in April, 1977, when she was found to have anemia and thrombocytopenia. Physical examination showed no 0rganomegaly or lymphadenopathy. The hemoglobin was 6.8 gm/d!, WBC 22,500/mm *, and plate!et count 26,000/mm 3. A bone marrow aspiration was diagnostic of ALL of non-T, non-B type, and remission was induced with vincristine, prednisone, and L'asparaginase therapy. After completion of CNS pr0phylax0022-3476/82/030422+03500.30/0 9 1982 The C. V. Mosby Co.