680
Letters to the Editor
presence of erythematous lesions on buccal mucosa in two of the children. ~ One of these two patients had traumatized the mucosa earlier in the day with a potato peeler, and we suggested that the abrasion may have been the source of her infection. Our current observations in Case 1 appear to support the hypothesis that bacteria in the mouth may directly invade the buccal soft tissues, particularly if preceeded by trauma. It is also possible that bacteremia was the primary event in this patient and that organisms settled at sites of tissue damage as appeared to Occur in Case 2. I would like to thank James Caffee, M.D. for permitting me to report Case 2. Dan M. Granoff,, M.D. Department of Pediatrics UCSF Medical Education Program Valley Medical Center of Fresno 445 S. Cedar Ave. Fresno, CA 93702 REFERENCES
1. Green M, and Fousek MD: Hemophilus influenzae type b cellulitis, Pediatrics 19:80, 1957. 2. Feingold M, and Gellis SS: Cellulitis due to Haemophilus influenzae type b, N Engl J Med 272:788, 1965. 3. Bada H, and Wright SP: Hemophilus influenzae cellulitis, Clin Pediatr 13:658, 1974. 4. Rapkin RH, and Bautista G: Hemophilus influenzae cellulitis, Am J Dis Child 124:540, 1972. 5. Alexander HE: Influenzae bacillus infections, in McIntosh HH, McIntosh LE, editors: Pediatrics, New York, 1953, Appleton-Century-Crofts, p 1200. 6. Nelson JC, and Ginsburg CM: An hypothesis on the pathogenesis of Hemophilus influenzae buccal cellulitis, J PEDIATR 88:709, 1976. 7. Granoff DM, and Nankervis GA: Cellulitis due to Haemophilus influenzae type b, Am J Dis Child 130:1211, 1976.
The Journal of Pediatrics October 1977
time revealed microscopic hematuria as well as mild proteinuria. A week later he developed anuria, and swelling of face and feet. Physical examination revealed moderate edema in the periorbital, pretibial, and sacral regions. The skin of the trunk and proximal extremities showed typical papulovesicular eruption of varicella in healing stage. Blood pressure was 160/110 mm Hg. Results of a systemic examination did not reveal any abnormality. Laboratory data included: hemoglobin, 10.5 gm/dl; leukocyte count, 6,500 cells/mm ~, with a normal differential cell count; normal peripheral blood smear;blood urea nitrogen, 150 mg/dl; creatinine, 12.5 mg/dl; total protein, 5.6 gm/dl (albumin, 2.6 gm; globulin, 3 gin). Normal values were found for platelets, prothrombin index, partial thromboplastin time with kaolin, thrombin time, euglobulin lysis time, and fibrinogen. Antistreptolysin O titer was 25 Todd units and did not show any rise subsequently. The serum complement values were within normal limits. Culture from a posterior pharyngeal swab showed no significant growth on two occasions. Since the patient continued to be progressively azotemic, he was given intermittent peritoneal dialysis. After four weeks of anuria, a percutaneous biopsy of the left kidney was performed; a total of 25 glomeruli was noted in the specimen. All the glomeruli showed hypercellnlarity and epithelial proliferation. Twenty-two glomeruli revealed formation of crescents. There was evidence of focal necrosis of glomerular tufts, with deposition of an eosinophilic hyaline substance. Tubules were dilated, and the interstitium showed focal infiltration with inflammatory cells. Immunofluorescence studies revealed diffuse granular IgG and C3 deposition involving peripheral capillary loops with variable mesangial involvement. Ten days later he started passing some urine (100 to 200 ml/day); the volume increased to 1,000 to 1,200 ml/day within a week. Ten peritoneal dialyses were performed during the annric phase (40 days). At re-evaluation two months after the varicella infection, he was normotensive and had no edema. Laboratory data obtained during that period: blood urea nitrogen, 20 mg/dl; serum creatinine, 2 mg/dl; creatinine clearance, 45 ml/minute/m 2. COMMENT
Rapidly progressive glomerulonephritis associated with varicella infection
Renal involvement is uncommon with varicella. 1 Renal lesions including proliferative glomerulonephritis as well as tubular necrosis have been reported in sporadic cases) We now describe a patient who developed rapidly progressive glomerulonephritis (RPGN) in association with varicella infection. Renal histology revealed characteristic features of crescentic glomerulonephritis. CASE REPORT
A 12-year-old boy was admitted to the hospital with the characteristic papular exanthem of chickenpox. Urinalysis at this
In a large series (2,534 cases) of varicella infection, only three patients with clinical nephritis were observed. 1 Occurrence of renal lesions in fatal cases of varicella infection have b e e n reported to be higher? Renal lesions consist of congested, hemorrhagic glomeruli, endothelial hyperplasia, and varying degree of tubular necrosis. 2 Krebs and Burvant 4 reported a case of nephrotic syndrome in association with varicella infection, the renal lesions included endothelial and epithelial hyperplasia in the glomeruli. There was no mention of the number of glomeruli with crescents. It was unlikely to be RPGN, since creatinine clearance did not fall significantly (92 ml/minute) and the clinical course of the disease was benign. P. C. Singhal, M.D. K. S. Chugh, M.D. M. A. Muthusethupatki, M.D. Department of Nephrology Postgraduate Institute of Medical Education & Research Chandigarh, India
Volume 91 Number 4
Letters to the Editor
REFERENCES
1. Bullowa JGM, and Wishik SM: Complications of varicella, Am J Dis Child 49:923, 1935. 2. Minkowttz S, Wenk R, Friedman E, Yuceoglu A, and Berkovich S: Acute glomerulonephritis associated with varicella infection, Am J Med 44:489, 1968. 3. Rotter R, and Collins JD: Fatal disseminated varicella in adults, Wis Med J 60:325, 1961. 4. Krebs RA, and Burvant MU: Nephrotic syndrome in association with varicella, JAMA 222:325, 1972.
Shunt arthritis
Hypocomplementemic glomerulonephritis is a well-known complication of infected ventriculoatrial (VA) shunts. We would like to call attention to an additional consequence of the immune complex formation resulting from such infections. The child reported below had arthralgia and arthritis for four years before he developed nephritis. CASE REPORT
In 1967, at age 6 months, this boy had a subdural-jugular shunt inserted to drain chronic subdural effusions secondary to head trauma. In 1971 he was noted to have intermittent leg pain with limping, splenomegaly, and anemia. In 1972 his physician observed a swollen left knee during an episode of bilateral knee and ankle pain. A diagnosis of juvenile rheumatoid arthritis (JRA) was made one year later when he developed unexplained fever, persistent arthralgia, and a positive rheumatoid factor (RF) test (1:160). Salicylate therapy resulted in improvement in the joint symptoms. In January, 1974, the RF titer had risen to 1:1280. He developed anasarca in March, 1975, and was transferred to State University Hospital. Laboratory values included: hemoglobin 7.5 gm/dl, erythrocyte sedimentation rate 68 ram/hour, total protein 5.0 gm/dl, albumin 2.5 gm/dl, CH~,0 11 units (normal 60-80), C3 41 mg/dl (normal 90-150), and 24-hour urine protein 3.5 gm. Three blood cultures were positive for Staphylococcus epidermidis as was the shunt catheter which was removed on the second hospital day. Although no antibiotic therapy was given, subsequent blood cultures were negative, fever did not recur, and the edema resolved during the 13 days of hospitalization. A percutaneous renal biopsy was consistent with Type l membranoproliferative (mesangiocapillary) glomerulonephritis. DISCUSSION The pathogenesis of "shunt nephritis" has been elucidated in recent studies? Chronic bacteremia, usually with Staphylococcus epidermidis elicits the formation of specific antibody and circulating immune complexes. The complement system is activated, and glomerular deposition of immunoglobulins, complement, and bacterial antigen leads to a diffuse glomerulonephritis. Antiglobulins (rheumatoid factors) are produced, probably in response to alteration of immunoglobulins in the process of combination with bacterial antigen. The same immunologic events occur in subacute bacterial
681
endocarditis (SBE), a disorder in which arthralgia and arthritis in the lower extremities are common early manifestations? Myers and Schumacher ~ recently demonstrated electron-dense deposits suggesting immune complexes on a synovial biopsy in SBE. Since SBE and chronic VA shunt infection lead to similar immunologic sequelae, one might expect musculoskeletal symptoms to precede the development of shunt nephritis in some patients. We believe that our patient's arthralgia and the arthritis noted on one occasion were secondary to such immune complex deposition. The occurrence of arthralgia and/or arthritis in patients with VA shunts may indicate the presence of shunt infection and should lead to appropriate diagnostic measures. Robert S. Pinals, M.D. Walter IV. Tunnessen Jr., M.D. Departments of Rehabilitation Medicine and Pediatrics State University of New York Upstate Medical Center 750 E. Adams St. Syracuse, N Y 13210 REFERENCES
1. Dobrin RS, Day NK, Quie PG, Moore HL, Vernier RL, Michael AF, and Fish A J: The role of complement, immunoglobulin and bacterial antigen in coagulase-negative staphylococcal shunt nephritis, Am J Med 59:660, 1975. 2. Churchill MA, Garaci JE, and Hunder GG: Musculoskeletal manifestations of bacterial endocarditis, Arthritis Rheum 20:111, 1977. 3. Myers AR, and Schumacher HR: Arthritis of subacute bacterial endocarditis, Arthritis Rheum 19:813, 1976.
Alternative complement pathway activity in cystic fibrosis
The possibility has been raised that complement plays a role in the pathogenesis of cystic fibrosis (CF)? Measurements of components of the complement system by Holzhauer and associates,=' Hann and associates? and Conover, Liebermann, and Scanlin (cited in reference 1) have yielded conflicting results. Policy and Bearn 4 found that inulin activation of the alternative pathway was less than 50% of normal controls in 10 of 11 CF patients studied. This impairment would be colasistent with the thesis that the alternative pathway had been activated in vivo and, therefore, depleted. The purpose of this work is to explore further the function of the alternative pathway in cystic fibrosis.
From the Department of Pediatrics, School of Medicine, The University of Alabama in Birmingham and The Children's Hospital. Supported by a center grant (R.E. 72) from the Cystic Fibrosis Foundation and by grants A I 10286 and CA 16673 from the National Institutes of Health.
Letters to the Editor
presence of erythematous lesions on buccal mucosa in two of the children. ~ One of these two patients had traumatized the mucosa earlier in the day with a potato peeler, and we suggested that the abrasion may have been the source of her infection. Our current observations in Case 1 appear to support the hypothesis that bacteria in the mouth may directly invade the buccal soft tissues, particularly if preceeded by trauma. It is also possible that bacteremia was the primary event in this patient and that organisms settled at sites of tissue damage as appeared to Occur in Case 2. I would like to thank James Caffee, M.D. for permitting me to report Case 2. Dan M. Granoff,, M.D. Department of Pediatrics UCSF Medical Education Program Valley Medical Center of Fresno 445 S. Cedar Ave. Fresno, CA 93702 REFERENCES
1. Green M, and Fousek MD: Hemophilus influenzae type b cellulitis, Pediatrics 19:80, 1957. 2. Feingold M, and Gellis SS: Cellulitis due to Haemophilus influenzae type b, N Engl J Med 272:788, 1965. 3. Bada H, and Wright SP: Hemophilus influenzae cellulitis, Clin Pediatr 13:658, 1974. 4. Rapkin RH, and Bautista G: Hemophilus influenzae cellulitis, Am J Dis Child 124:540, 1972. 5. Alexander HE: Influenzae bacillus infections, in McIntosh HH, McIntosh LE, editors: Pediatrics, New York, 1953, Appleton-Century-Crofts, p 1200. 6. Nelson JC, and Ginsburg CM: An hypothesis on the pathogenesis of Hemophilus influenzae buccal cellulitis, J PEDIATR 88:709, 1976. 7. Granoff DM, and Nankervis GA: Cellulitis due to Haemophilus influenzae type b, Am J Dis Child 130:1211, 1976.
The Journal of Pediatrics October 1977
time revealed microscopic hematuria as well as mild proteinuria. A week later he developed anuria, and swelling of face and feet. Physical examination revealed moderate edema in the periorbital, pretibial, and sacral regions. The skin of the trunk and proximal extremities showed typical papulovesicular eruption of varicella in healing stage. Blood pressure was 160/110 mm Hg. Results of a systemic examination did not reveal any abnormality. Laboratory data included: hemoglobin, 10.5 gm/dl; leukocyte count, 6,500 cells/mm ~, with a normal differential cell count; normal peripheral blood smear;blood urea nitrogen, 150 mg/dl; creatinine, 12.5 mg/dl; total protein, 5.6 gm/dl (albumin, 2.6 gm; globulin, 3 gin). Normal values were found for platelets, prothrombin index, partial thromboplastin time with kaolin, thrombin time, euglobulin lysis time, and fibrinogen. Antistreptolysin O titer was 25 Todd units and did not show any rise subsequently. The serum complement values were within normal limits. Culture from a posterior pharyngeal swab showed no significant growth on two occasions. Since the patient continued to be progressively azotemic, he was given intermittent peritoneal dialysis. After four weeks of anuria, a percutaneous biopsy of the left kidney was performed; a total of 25 glomeruli was noted in the specimen. All the glomeruli showed hypercellnlarity and epithelial proliferation. Twenty-two glomeruli revealed formation of crescents. There was evidence of focal necrosis of glomerular tufts, with deposition of an eosinophilic hyaline substance. Tubules were dilated, and the interstitium showed focal infiltration with inflammatory cells. Immunofluorescence studies revealed diffuse granular IgG and C3 deposition involving peripheral capillary loops with variable mesangial involvement. Ten days later he started passing some urine (100 to 200 ml/day); the volume increased to 1,000 to 1,200 ml/day within a week. Ten peritoneal dialyses were performed during the annric phase (40 days). At re-evaluation two months after the varicella infection, he was normotensive and had no edema. Laboratory data obtained during that period: blood urea nitrogen, 20 mg/dl; serum creatinine, 2 mg/dl; creatinine clearance, 45 ml/minute/m 2. COMMENT
Rapidly progressive glomerulonephritis associated with varicella infection
Renal involvement is uncommon with varicella. 1 Renal lesions including proliferative glomerulonephritis as well as tubular necrosis have been reported in sporadic cases) We now describe a patient who developed rapidly progressive glomerulonephritis (RPGN) in association with varicella infection. Renal histology revealed characteristic features of crescentic glomerulonephritis. CASE REPORT
A 12-year-old boy was admitted to the hospital with the characteristic papular exanthem of chickenpox. Urinalysis at this
In a large series (2,534 cases) of varicella infection, only three patients with clinical nephritis were observed. 1 Occurrence of renal lesions in fatal cases of varicella infection have b e e n reported to be higher? Renal lesions consist of congested, hemorrhagic glomeruli, endothelial hyperplasia, and varying degree of tubular necrosis. 2 Krebs and Burvant 4 reported a case of nephrotic syndrome in association with varicella infection, the renal lesions included endothelial and epithelial hyperplasia in the glomeruli. There was no mention of the number of glomeruli with crescents. It was unlikely to be RPGN, since creatinine clearance did not fall significantly (92 ml/minute) and the clinical course of the disease was benign. P. C. Singhal, M.D. K. S. Chugh, M.D. M. A. Muthusethupatki, M.D. Department of Nephrology Postgraduate Institute of Medical Education & Research Chandigarh, India
Volume 91 Number 4
Letters to the Editor
REFERENCES
1. Bullowa JGM, and Wishik SM: Complications of varicella, Am J Dis Child 49:923, 1935. 2. Minkowttz S, Wenk R, Friedman E, Yuceoglu A, and Berkovich S: Acute glomerulonephritis associated with varicella infection, Am J Med 44:489, 1968. 3. Rotter R, and Collins JD: Fatal disseminated varicella in adults, Wis Med J 60:325, 1961. 4. Krebs RA, and Burvant MU: Nephrotic syndrome in association with varicella, JAMA 222:325, 1972.
Shunt arthritis
Hypocomplementemic glomerulonephritis is a well-known complication of infected ventriculoatrial (VA) shunts. We would like to call attention to an additional consequence of the immune complex formation resulting from such infections. The child reported below had arthralgia and arthritis for four years before he developed nephritis. CASE REPORT
In 1967, at age 6 months, this boy had a subdural-jugular shunt inserted to drain chronic subdural effusions secondary to head trauma. In 1971 he was noted to have intermittent leg pain with limping, splenomegaly, and anemia. In 1972 his physician observed a swollen left knee during an episode of bilateral knee and ankle pain. A diagnosis of juvenile rheumatoid arthritis (JRA) was made one year later when he developed unexplained fever, persistent arthralgia, and a positive rheumatoid factor (RF) test (1:160). Salicylate therapy resulted in improvement in the joint symptoms. In January, 1974, the RF titer had risen to 1:1280. He developed anasarca in March, 1975, and was transferred to State University Hospital. Laboratory values included: hemoglobin 7.5 gm/dl, erythrocyte sedimentation rate 68 ram/hour, total protein 5.0 gm/dl, albumin 2.5 gm/dl, CH~,0 11 units (normal 60-80), C3 41 mg/dl (normal 90-150), and 24-hour urine protein 3.5 gm. Three blood cultures were positive for Staphylococcus epidermidis as was the shunt catheter which was removed on the second hospital day. Although no antibiotic therapy was given, subsequent blood cultures were negative, fever did not recur, and the edema resolved during the 13 days of hospitalization. A percutaneous renal biopsy was consistent with Type l membranoproliferative (mesangiocapillary) glomerulonephritis. DISCUSSION The pathogenesis of "shunt nephritis" has been elucidated in recent studies? Chronic bacteremia, usually with Staphylococcus epidermidis elicits the formation of specific antibody and circulating immune complexes. The complement system is activated, and glomerular deposition of immunoglobulins, complement, and bacterial antigen leads to a diffuse glomerulonephritis. Antiglobulins (rheumatoid factors) are produced, probably in response to alteration of immunoglobulins in the process of combination with bacterial antigen. The same immunologic events occur in subacute bacterial
681
endocarditis (SBE), a disorder in which arthralgia and arthritis in the lower extremities are common early manifestations? Myers and Schumacher ~ recently demonstrated electron-dense deposits suggesting immune complexes on a synovial biopsy in SBE. Since SBE and chronic VA shunt infection lead to similar immunologic sequelae, one might expect musculoskeletal symptoms to precede the development of shunt nephritis in some patients. We believe that our patient's arthralgia and the arthritis noted on one occasion were secondary to such immune complex deposition. The occurrence of arthralgia and/or arthritis in patients with VA shunts may indicate the presence of shunt infection and should lead to appropriate diagnostic measures. Robert S. Pinals, M.D. Walter IV. Tunnessen Jr., M.D. Departments of Rehabilitation Medicine and Pediatrics State University of New York Upstate Medical Center 750 E. Adams St. Syracuse, N Y 13210 REFERENCES
1. Dobrin RS, Day NK, Quie PG, Moore HL, Vernier RL, Michael AF, and Fish A J: The role of complement, immunoglobulin and bacterial antigen in coagulase-negative staphylococcal shunt nephritis, Am J Med 59:660, 1975. 2. Churchill MA, Garaci JE, and Hunder GG: Musculoskeletal manifestations of bacterial endocarditis, Arthritis Rheum 20:111, 1977. 3. Myers AR, and Schumacher HR: Arthritis of subacute bacterial endocarditis, Arthritis Rheum 19:813, 1976.
Alternative complement pathway activity in cystic fibrosis
The possibility has been raised that complement plays a role in the pathogenesis of cystic fibrosis (CF)? Measurements of components of the complement system by Holzhauer and associates,=' Hann and associates? and Conover, Liebermann, and Scanlin (cited in reference 1) have yielded conflicting results. Policy and Bearn 4 found that inulin activation of the alternative pathway was less than 50% of normal controls in 10 of 11 CF patients studied. This impairment would be colasistent with the thesis that the alternative pathway had been activated in vivo and, therefore, depleted. The purpose of this work is to explore further the function of the alternative pathway in cystic fibrosis.
From the Department of Pediatrics, School of Medicine, The University of Alabama in Birmingham and The Children's Hospital. Supported by a center grant (R.E. 72) from the Cystic Fibrosis Foundation and by grants A I 10286 and CA 16673 from the National Institutes of Health.
