Congenital lymphedema and yellow nails

454

Brie[ clinical and laboratory observations

phosphamide therapy. T h e effect of the earlier fom'-day course of cyclophosphamide cannot be determined. The short time interval between recovery from initial varicella and reinstituting cyclophosphamide therapy may have had a role in the reactivation of varicella. A more critical factor may be the severe, prolonged lymphopenia induced by cyclophosphamide 11 days before reactivation of varicella. There is no evidence that effectiveness in controlling nephrosis with cyclophosphamide is related to leukopenia, although this has been suggested?' It, is recommended that children who are candidates for cyclophosphamide therapy, because of steroid-resistant or steroid-dependent nephrosis, be evaluated by history and serologic data to determine if adequate imnmnity exists to varicella and measles. Consideration must be given to withholding cyclophosphamide in the child lacking immunity until natural or vaccine induced immunity develops. Recent reports of sterility with testicular atrophy in males, and amenorrhea in females after cyclophosphamide therapy, ~2 emphasize another risk in the use of cyclophosphamide in children with nephrosis. We are grateful to Drs. William L. Nyhan, University of California, San Diego, for the amino acid determinations, P. L. Baseley, University of California, San Diego, for the varicella antibody titers, and T. S. Edgington, Scripps Clinic and Research Foundation, La Jolla, for

Congenital lymphedema and yellow nails Paul K. Kleinman, M.D., N e w York, N. Y.

From the Department o[ Pediatrics, Cornell University Medical College, and The New York Hospital-Cornell Medical Center. Supported in part by United States Public Health Service, Division o[ Research Facilities and Resources, Clinical Research Center Grant Award RR47. Reprint address: 525 E. 68th St., Nezo York, N. Y. 10021.

The Journal o[ Pediatrics September 1973

the immunofluorescence studies of the renal biopsy. REFERENCES

1. Etteldorf, J. N., Roy, S., III, Summitt, R. L., Sweeney, M. J., Wall, H. P., and Berton, W. M.: Cyclophosphamide in the treatment of idiopathic lipoid nephrosis, J. PEDIATR.70: 758, 1967. 2. Grunberg, J.: Cyclophosphamide therapy for nephrosis, J. PEI)IATR.73: 641, 1968 (Letter.) 3. Scheinman, J. I., and Stamler, F. W.: Cyelophosphamide and fatal varicella, J. PeDIATR. 74: 117, 1969. 4. Yuceoglu, A. M., Berkovich, S., and Chiu, J.: Effect of live measles virus vaccine on childhood nephrosis, J. PEDIATr~.74: 291, 1969. 5. Falliers, C. J., and Ellis, E. F.: Corticosteroids and varicella, Arch. Dis. Child. 40: 593, 1965. 6. Shee, J. C., and Fehrsen, P.: Reactivation of varicella by cortisone therapy, Br. Med. J. 2: 82, 1953. 7. Crisalli, M., and Terragna, A.: Modificazioni indotte dal cortisone sull'esantema varicelloso, Gazz. Sanit. Milano 27: 297, 1956. 8. Churg, J., Habib, R., and White, R. H. R.: Pathology of the nephrotic syndrome in children, Lancet 1: 1299, 1970. 9. Lux, S. E., Johnston, Jr., R. B., August, C. S., Say, B., Penchszadeh, V. B., Rosen, K. S., and McKusick, V. A.: Chronic neutropenia and abnormal cellular immunity in cartilage-hair hypoplasia, N. Engl. J. Med. 282: 231, 1970. 10. Meadow, S. R., Weller, R. O., and Archibald, R. W. R.: Fatal systemic measles in a child receiving cyclophosphamide for nephrotic syndrome, Lar, cet 2: 876, 1969. 11. White, R. H. R.: Cytotoxic drug therapy in steroid-resistant glomerulonephritis, Proe. R. Soc. Med. 60: 1164, 1967. 12. Fairley, K. F., Barrie, J. U., and Johnson, W.: Sterility and testicular atrophy related to cyclophosphamide therapy, Lancet 1: 568, 1972.

S A M M A N and White ~ first noted the association of primary lymphedema and yellow nails and called it the yellow nail syndrome. It has subsequently been reported in 19 patients, 2-~ but has received little attention in the pediatric literature. A patient reported by Zerfas, ~ and one described by Midana and associates ~ had lymphedema and yellow nails which were said to have begun in childhood, but there has been no documented report of the syndrome in a child. This report describes a case of the yellow nail syndrome in a child with congenital lymphedema.

Volume 83 Number 3

CASE R E P O R T This l ly2-year-old Ecuadorian girl had bilateral edema of the lower extremities since birth and several reported episodes of swelling of the face and anterior chest wall in early childhood. She had no ulceration or infection. Yellow toenails, requiring infrequent cutting, were noted several years prior to admission. An episode of "hepatitis" occurred three years earlier. A sister died at four months of age, apparently with total body edema. A roentgenogram taken in March, 1972, revealed a density overlying the right lobe of the lung, and roentgenograms over the next four months showed the possible presence of free fluid associated with this density. In July, 1972, she was admitted to The New York Hospital for investigation. She had mild ocular hypertelorism. There was dullness to percussion at the right base anteriorly. The labia minora and clitoral prepuce were redundant. There was bilateral slightly pitting edema of the legs and feet, right greater than left. The toenails were dull yellow and opaque wi{h accentuated convexity; they obscured the normally pink nail bed, but the lunula could still be identified. The large toenails were thickened and showed cross ridging, but the fingernails were normal in color and form. The remainder of the physical examination was unremarkable. The hemogram, urinalysis, and serum chemical values were normal. A test for hepatitisassociated antigen was negative. Urinary protein excretion per 12 hours was normal. Second strength purified protein derivative, blastomyeosis, coccidioidomycosis, and histoplasmosis skin tests were negative. Chromium'~Mabeled albumin infusion showed no abnormal gastrointestinal loss of protein. Upper gastrointestinal and small bowel series showed a normal mucosal pattern. Roundworms were seen in the ileum and jejunum, and Ascaris eggs were identified in a stool specimen. Chromosome analysis showed a normal female karyotype. Surgical exploration of the dorsum of both feet following the subcutaneous administration of blue dye revealed no discernible lymphatic vessels. An inferior vena cavagram was normal. Right-sided thoracentesis from anterior and posterior approaches revealed no fluid. She was treated with support stockings, elastic bandages, and elevation at night, and she had a visible decrease of leg edem'a. The Ascaris infestation was successfully treated with thiabendazole.

Brief clinical and laboratory obsereations

455

DISCUSSION I n 1960, Lorber a n d Illingworth 1~ and Jones 11 described several children with l y m p h e d e m a a n d incidentally mentioned dystrophic toenails, b u t not u n t i l 1964 did S a m m a n and White l link p r i m a r y lymphedema with a characteristic abnormality of the nails. They described pale yellow to slightly green nails with accentuated convexity, slow rate of growth, and cross ridging, a n d suggested that the changes were due to a defect in the lymphatic drainage of the fingers a n d toes. T h e yellow nails are not only of interest because they may represent a n o t h e r manifestation of a b n o r m a l lymphatic vessels in a patient evidencing lymphedema. T h e y may, in fact, precede the development of the l y m p h e d e m a by as m u c h as five yearsY T h e i r presence in an otherwise n o r m a l individual should alert one to the possibility of subseq u e n t edema formation. A family history of l y m p h e d e m a in a child should p r o m p t careful examination of the finger- a n d toenails, even in the absence of clinical edema. The author wishes to thank Drs. Wallace McCrory and John Ribble for their thoughtful criticism of the manuscript. REFERENCES 1. Samman, P. D., and White, W. F.: The "yellow nail" syndrome, Br. J. Dermatol. 76: 153, 1964. 2. Wells, G. C.: Yellow nail syndrome: With familial primary hypoplasia of lymphatics, manifest late in life, Proc. R. Soc. Med. 59: 447, 1966. 3. Zerfas, A. J.: Yellow nail syndrome with bilateral bronchietasis, Proc. R. Soc. Med. 59: 448, 1966. 4. Emerson, P. A.: Yellow nails, lymphoedema, and pleural effusions, Thorax 21: 247, 1966. 5. Dilley, J. J., Kiertand, R. R., Randall, R. V., and Shick, R. M.: Primary lymphedema associated with yellow nails and pleural effusions, J. A. M. A. 204: 670, 1968. 6. Bowers, D.: Unequal breasts, yellow nails, bronehiectasis and lymphedema, Can. Med. Assoc. J. 100: 437, 1969. 7. Siegelman, S. S., Heckman, B. H., and Hasson, J.: Lymphedema, pleural effusions and yellow nails, Dis. Chest 56: 116, 1969. 8. D'Souza, M. F.: Generalized lymphoedema with yellow nails, pleural effusions and macroglobulinaemia, Proc. R. Soc. Med. 63: 456, 1970.

456

Brief clinical and laboratory observations

9. Midana, A., Zina, G., and Mazza, C.: "Lymphoedema" primaire associ6 aux epanchements pleuraux et aux ongl6s jaunes (The Yellow Nails de Samman et White), Bull. Fr. Dermatol. Syphiligr. 78: 225, 1971.

Transient obstructive uropathy associated with the nephrotic syndrome.. Case report Michael Berger, M.D., L u t h e r B. Travis, M.D., William B. Lorentz, Jr., M.D., and Hugo F. Carvajal, M.D., Galveston, Texas

H Y D R O U R E T E R O N EP I~RO S IS i n t h e absence of demonstrable fixed anatomic obstruction is unusual. T h e present report describes a patient with the nephrotic syndrome in whom hydronephrosis developed and cleared without surgical intervention. Physicians should be aware of this previously unreported possibility so that medical m a n agement is not forsaken too soon in favor of surgical intervention.

CASE REPORT Patient B. R., a 12-year-old Negro boy, was recently readmitted to the University of Texas Medical Branch Hospital for evaluation of "frequently relapsing nephrotic syndrome. The diagnosis was made initially in April, 1963, when he presented with massive proteinuria, hypoalbuFrom the Department of Pediatrics, Division of Nephrology, University of Texas Medical Branch. Supported in part by the Academic Training Grant DHEW 5TO1 HD 00267 (04). Some of these studies were per[ormed during hospitalization in the Clinical Study Center, University of Texas Medical Branch, under support of Department o[ Health, Education, and Wel[are Grant RR-73. Reprint address: Department o[ Pediatrics, Division o[ Nephrology, University,of Texas Medical Branch, Galveston, Texas 77550.

2"he Journal o[ Pediatrics September 1973

10. Lorber, J., and Illingworth, R. S.: Generalized oedema of obscure origin, Acta Paediatr. Scand. 49" 748, 1960. 11. Jones, H. E.: Symmetrical periferal oedema in infants, Arch. Dis. Child. 35: 192, 1960.

minemia, elevated plasma cholesterol, and edema. A renal biopsy specimen was interpreted as being indicative of the minimal-lesion variety of lipoid nephrosis. Intravenous pyelography was normal. Following an initial response to standard glucocorticoid therapy, he began to have frequent exacerbations of proteinuria and edema; each required reinstitution of steroid therapy. He subsequently received two courses of cyclophosphamide (1966 and 1967) ill attempts to prolong remission; neither course was particularly successful in accomplishing this goal. The patient was again admitted to the hospital in July, 1968, when a renal biopsy demonstrated no progression of his renal lesion, and laboratory studies revealed normal renal function. An intravenous pyelogram showed an irregular appearance of the calyceal fomices; this was thought to be a morphologic variant. Multiple urine cultures during this admission were sterile. Between July, 1968, and the present admission (August, 1972), he continued to have frequent recurrences of proteinuria and edema whenever maintenance steroid dosage was decreased to less than 30 mg. every other day. At the time of each recurrence of edema, daily administration of the steroid was resumed. At the time of the present admisslon, he was in the midst of an exacerbation and had been receiving prednisone daily for two weeks without noticeable reduction in the degree of proteinuria. Physical examination revealed him to have a markedly cushingoid appearance. Blood pressure was 138/85, and there was moderate generalized edema. Significant laboratory data included: massive proteinuria (4.2 Gin. per 24 hours), a total serum protein of 5.9 Gm. per cent (albumin 2.1 Gm. per cent), and a serum cholesterol concentration of 485 mg. per cent. His glomerular filtration rate, measured by inulin clearance, was 55 ml. per minute per square meter of body surface area (normal 60 to 80 ml. per minute per square meter). Renal histology revealed mild mesangial sclerosis, epithelial cell pedocyte fusion, and mild vacuolization of the endothelial cell cytoplasm. An intravenous pyelogram (Fig. 1) showed bilateral hydronephrosis and hydroureter which were more marked on the left. A voiding cysto-