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Acute interstitial nephritis and iritis
Acute Interstitial Nephritis and lritis Renal-Ocular Syndrome
THEODORE I. STEINMAN, M.D. PATRICIO
SILVA,
M.D.
Boston, Messechusetts
Acute renal failure developed in a prevlously healthy woman in association with acute lrltis. Renal biopsy revealed acute mononuclear interstitial nephrltls. Known systemic Illnesses that can present as acute renal fatlure and have ocular manifestations of lrltls/uveltls were excluded by detailed testing and observation during a 24-month period. No cause for this renal-ocular syndrome was discovered. There was a dramatic Improvement to normal renal function and complete resolution of ocular findings following a two-month course of steroid therapy. Acute interstitial nephritis is not commonly associated with iritis/ uveitis. Although iritisiuveitis may occur as a manifestation of a variety of systemic illnesses [I], it is unusual for those diseases to be complicated by acute interstitial nephritis. Disorders in which eye findings may be prominent include tuberculosis [2], sarcoidosis [3], Wegener’s granulomatosis [4], collagen vascular disorders [ 51, Behcet’s disease [6], StevensJohnson syndrome, and infectious diseases such as syphilis [2,7], toxoplasmosis [8], cytomegalovirus infection [9], infectious mononucleosis [5], herpes simplex virus infection [lo], Chlamydia psittaci infection [Ill, and leprosy [ 121. Dobrin et al [ 131 described two patients with acute eosinophilic interstitial nephritis and renal failure associated with bone marrow and lymph node granulomas and anterior uveitis of unknown cause. We describe herein a patient with acute mononuclear cell interstitial nephritis with iritis, but no bone marrow granulomas, in whom no obvious cause for the constellation of findings was determined. Treatment with steroids resulted in rapid improvement. CASE REPORT
From the Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of Beth Israel Hospital, Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts. Requests for reprints should be addressed to Dr. Theodore I. Steinman. Department of Medicine, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215. Manuscript accepted September 28, 1983.
A 27-year-old, single, mental health worker has been in excellent health her entire life except for scoliosis corrected by surgery. All laboratory results were within normal limits three years prior to the present illness during her hospitalization for surgery. One month prior to admission, a slight nonproductive cough, lethargy, myalgias, weight loss, and a fever of 102OF developed. She took one aspirin per day for her symptoms. On admission to the hospital, her blood pressure was 90170 mm Hg. The only abnormal findings on examination were conjunctival/scleral injection of her right eye, and bilateral enlargement of the posterior cervical and inguinal lymph nodes. Ophthalmologic consultation documented the presence of acute iritis with no signs of posterior uveitis. Creatinine was 2.0 mg/dl, blood urea nitrogen 33 mg/dl, hematocrit 30 percent, hemoglobin 10.2 g/dl, red blood cell count 3,380,000/mm3, and white blood cell count 8,900/mm3, with 68 percent polymorphonuclear leukocytes, 31 percent lymphocytes, and 1 percent eosinophils. The eryth-
July 1984
The American Journal of Medlclne
Volume 77
189
ACUTE RENAL FAILURE AND IRITIS-STEINMAN and SlLVA
rocyte sedimentation rate was 40 mm per hour (Westergren). Urinalysis revealed 1.013 specific gravity, 6.0 pH, l-i- protein, trace glucose, one or two red blood cells, 25 to 30 white blood cells, white blood cell casts, coarsely granular casts, and 1+ bacteriuria. Wright’s stain of her urine showed no eosinophiluria. Urine culture revealed no growth in 48 hours. The 24-hour urine protein excretion was 1.2 g, and the calculated creatinine clearance was 60 ml/minute/l.73 m*. The complement studies revealed a minimal elevation of the CH50 and C4 values, with a normal C3 value. Chest radiography revealed a slight dorsal scoliosis with two Harrington rods in place. The heat-I and mediastinum were not enlarged, and the lungs were clear. Serologic results for Epstein-Barr virus, cytomegalovirus, herpes simplex virus, rubella, and Toxoplasma were negative or revealed no change in titer between acute and convalescent samples. The mono spot test gave negative results, and the serologic test for syphilis (VDRL) was nonreactive. Intermediate-strength purified protein derivative gave negative results at 48 hours. Blood, sputum, urine, and stool cultures, including those for brucellosis, tuberculosis, and leptospirosis, showed no growth.
After three weeks’ observation, there was no improvement in her renal function, and fever persisted. Slight improvement in her eye condition occurred with topical steroid administration and atropine eyedrops. Percutaneous renal biopsy revealed acute interstitial nephritis with an abundance of mononuclear cells, plasma cells, and a few polymorphonuclear leukocytes. There were few eosinophils. The mononuclear cells were infiltrating the tubules (many lined by low cuboidal epithelium), and the tubular epithelial cells showed degenerative changes. The vessels and glomeruli were unremarkable. The findings were most consistent with acute mononuclear cell interstitial nephritis. Bone marrow biopsy revealed no abnormalities. For one month, she continued to have abnormal renal function with proteinuria and serum creatinine values in the range of 2.0 mg/dl on repeated determinations. Because of ongoing malaise, incomplete resolution of her eye findings, and anemia, she began receiving prednisone, 60 mg per day. Over one month, the dosage was tapered to 30 mg per day and then switched to alternate-day therapy for an additional month before it was tapered to discontinuation. During the second week of prednisone therapy, there was a dramatic improvement in her symptoms, and the serum creatinine Values fell to 1.3 mg/dl. One month after steroid therapy had
been started, her renal function was normal, with a serum creatinine value of 0.8 mg/dl, her hematocrit had increased to 38 percent, the proteinuria disappeared, and the persis-
tently abnormal urine sediment normalized.
The patient was followed up for 24 months after discontinuation of steroids, and she remained in her usual state of good health. There was a complete resolution of her eye condition. In the follow-up period, there were no symptoms or signs suggesting a systemic illness. COMMENTS This patient had acute mononuclear cell interstitial nephritis and iritis, presumably related to a viral-like illness. However, serologic results were negative for those viruses known to be associated with iritisjuveitis (Epstein-Barr virus, cytomegalovirus, herpes simplex virus, and rubella) and Toxoplasma. All cultures were sterile. She had no exposure to any medications or drugs except for a single aspirin tablet per day. The patient had no rashes, eosinophilia, or eosinophiluria. Systemic illnesses known to be associated with either uveitis or iritis [l-13] were not present by either clinical criteria or laboratory investigation. Despite her minimal cough, which resolved rapidly with steroids, the chest radiographic findings were normal. The diagnosis of sarcoidosis seemed unlikely. At no time was there mediastinal lymph node enlargement, hepatic dysfunction, or hypercalcemia. The negative tuberculin test result and the normal chest radiographic appearance militated against a diagnosis of tuberculosis. No evidence of any collagen vascular disease or vasculitis was noted on the initial evaluation or during the 24 months of close follow-up. There were no skin or mucous membrane lesions to suggest Behcet’s disease [6] or the StevensJohnson syndrome. Because of the article by Dobrin et al [ 131, bone marrow biopsy was performed to search for granulomas, but none was found. The patients previously described had eosinophilic interstitial nephritis, in contrast to our patient who had mononuclear cell interstitial infiltration. There was a dramatic response to prednisone treatment tapered to discontinuation over two months. In conclusion, it appears that our patient had acute mononuclear cell interstitial nephritis and iritis associated with a systemic disease. Response to steroid therapy was dramatic. Patients with this renal-ocular constellation may show significant response to a short-term course of steroids.
REFERENCES 1.
James DG: Uveitis is a systemic disorder (editorial). Am J Med
2.
1978; 65: 567-568. Schlaegel TF Jr, O’Connor GR: Tuberculosis and syphilis
3.
(letter). Arch Ophthalmol 1981; 99: 2206-2207. Perkins ES: Ocular sarcoidosis (editorial). Arch Ophthalmol
4.
190
1981; 99: 1193. Haynes BF, Fishman ML, Fauci AS, Wolff SM: The ocular manifestations of Wegener’s granulomatosis. Fifteen years
July 1984
The American Journal of Medlclne
Volume 77
experience and review of the literature. Am J Med 1977; 63: 131-141.
5.
O’Connor GR: Current concepts in ophthalmology. Uveitis and the immunolcgically compromised host N EnglJ Med 1978; 299: 130-132.
6.
Colvard DM, Robertson DM. O’Duffy JD: The ocular manifestations of Behcet’s disease. Arch Ophthalmol 1977; 95: 1813-1817.
ACUTE RENAL FAILURE AND IRITIS-STEINMAN
7. 8.
9.
10.
Ross WH, Sutton HF: Acquired syphilitic uveitis. Arch Ophthalmol 1980; 98: 498-498. Rao NA, Font RL: Toxoplasmic retinochoroiditis: electronmicroscopic and immunofluorescence studies of formalin-fixed tissue. Arch Ophthalmol 1977; 95: 273-277. Guignard JP, Torrado A: Interstitial nephritis and toxoplasmosis in a lo-vear-old child. J Pediatr 1974; 85: 38% 382. Sumers KD, Sugar J, Levine R: Endogenous dissemination of genital herpes virus hominis type 2 to the eye. Br J Ophthalmol 1980; 64: 770-772.
11.
12. 13.
and SILVA
Darougar S, John AC, Viswalingam M, Cornell L, Jones BR: Isolation of chlamydia psittaci from a patient with interstiiial keratitis and uveitis associated with otological and cardiovascular lesions. Br J Ophthalmol 1978; 62: 709714. Shields JA, Waring GD Ill, Monte LG: Ocular findings in leprosy. Am J Oohthalmol 1974; 77: 880-890. Dobrin RS; Vernier RL, Fish AL: Acute eosinophilic interstitial nephritis and renal failure with bone marrow-lymph node granulomas and anterior uveitis. A new syndrome. Am J Med 1975; 59: 325-333.
July 1994
The American Journal of Medlclne
Volume 77
191
THEODORE I. STEINMAN, M.D. PATRICIO
SILVA,
M.D.
Boston, Messechusetts
Acute renal failure developed in a prevlously healthy woman in association with acute lrltis. Renal biopsy revealed acute mononuclear interstitial nephrltls. Known systemic Illnesses that can present as acute renal fatlure and have ocular manifestations of lrltls/uveltls were excluded by detailed testing and observation during a 24-month period. No cause for this renal-ocular syndrome was discovered. There was a dramatic Improvement to normal renal function and complete resolution of ocular findings following a two-month course of steroid therapy. Acute interstitial nephritis is not commonly associated with iritis/ uveitis. Although iritisiuveitis may occur as a manifestation of a variety of systemic illnesses [I], it is unusual for those diseases to be complicated by acute interstitial nephritis. Disorders in which eye findings may be prominent include tuberculosis [2], sarcoidosis [3], Wegener’s granulomatosis [4], collagen vascular disorders [ 51, Behcet’s disease [6], StevensJohnson syndrome, and infectious diseases such as syphilis [2,7], toxoplasmosis [8], cytomegalovirus infection [9], infectious mononucleosis [5], herpes simplex virus infection [lo], Chlamydia psittaci infection [Ill, and leprosy [ 121. Dobrin et al [ 131 described two patients with acute eosinophilic interstitial nephritis and renal failure associated with bone marrow and lymph node granulomas and anterior uveitis of unknown cause. We describe herein a patient with acute mononuclear cell interstitial nephritis with iritis, but no bone marrow granulomas, in whom no obvious cause for the constellation of findings was determined. Treatment with steroids resulted in rapid improvement. CASE REPORT
From the Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of Beth Israel Hospital, Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts. Requests for reprints should be addressed to Dr. Theodore I. Steinman. Department of Medicine, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215. Manuscript accepted September 28, 1983.
A 27-year-old, single, mental health worker has been in excellent health her entire life except for scoliosis corrected by surgery. All laboratory results were within normal limits three years prior to the present illness during her hospitalization for surgery. One month prior to admission, a slight nonproductive cough, lethargy, myalgias, weight loss, and a fever of 102OF developed. She took one aspirin per day for her symptoms. On admission to the hospital, her blood pressure was 90170 mm Hg. The only abnormal findings on examination were conjunctival/scleral injection of her right eye, and bilateral enlargement of the posterior cervical and inguinal lymph nodes. Ophthalmologic consultation documented the presence of acute iritis with no signs of posterior uveitis. Creatinine was 2.0 mg/dl, blood urea nitrogen 33 mg/dl, hematocrit 30 percent, hemoglobin 10.2 g/dl, red blood cell count 3,380,000/mm3, and white blood cell count 8,900/mm3, with 68 percent polymorphonuclear leukocytes, 31 percent lymphocytes, and 1 percent eosinophils. The eryth-
July 1984
The American Journal of Medlclne
Volume 77
189
ACUTE RENAL FAILURE AND IRITIS-STEINMAN and SlLVA
rocyte sedimentation rate was 40 mm per hour (Westergren). Urinalysis revealed 1.013 specific gravity, 6.0 pH, l-i- protein, trace glucose, one or two red blood cells, 25 to 30 white blood cells, white blood cell casts, coarsely granular casts, and 1+ bacteriuria. Wright’s stain of her urine showed no eosinophiluria. Urine culture revealed no growth in 48 hours. The 24-hour urine protein excretion was 1.2 g, and the calculated creatinine clearance was 60 ml/minute/l.73 m*. The complement studies revealed a minimal elevation of the CH50 and C4 values, with a normal C3 value. Chest radiography revealed a slight dorsal scoliosis with two Harrington rods in place. The heat-I and mediastinum were not enlarged, and the lungs were clear. Serologic results for Epstein-Barr virus, cytomegalovirus, herpes simplex virus, rubella, and Toxoplasma were negative or revealed no change in titer between acute and convalescent samples. The mono spot test gave negative results, and the serologic test for syphilis (VDRL) was nonreactive. Intermediate-strength purified protein derivative gave negative results at 48 hours. Blood, sputum, urine, and stool cultures, including those for brucellosis, tuberculosis, and leptospirosis, showed no growth.
After three weeks’ observation, there was no improvement in her renal function, and fever persisted. Slight improvement in her eye condition occurred with topical steroid administration and atropine eyedrops. Percutaneous renal biopsy revealed acute interstitial nephritis with an abundance of mononuclear cells, plasma cells, and a few polymorphonuclear leukocytes. There were few eosinophils. The mononuclear cells were infiltrating the tubules (many lined by low cuboidal epithelium), and the tubular epithelial cells showed degenerative changes. The vessels and glomeruli were unremarkable. The findings were most consistent with acute mononuclear cell interstitial nephritis. Bone marrow biopsy revealed no abnormalities. For one month, she continued to have abnormal renal function with proteinuria and serum creatinine values in the range of 2.0 mg/dl on repeated determinations. Because of ongoing malaise, incomplete resolution of her eye findings, and anemia, she began receiving prednisone, 60 mg per day. Over one month, the dosage was tapered to 30 mg per day and then switched to alternate-day therapy for an additional month before it was tapered to discontinuation. During the second week of prednisone therapy, there was a dramatic improvement in her symptoms, and the serum creatinine Values fell to 1.3 mg/dl. One month after steroid therapy had
been started, her renal function was normal, with a serum creatinine value of 0.8 mg/dl, her hematocrit had increased to 38 percent, the proteinuria disappeared, and the persis-
tently abnormal urine sediment normalized.
The patient was followed up for 24 months after discontinuation of steroids, and she remained in her usual state of good health. There was a complete resolution of her eye condition. In the follow-up period, there were no symptoms or signs suggesting a systemic illness. COMMENTS This patient had acute mononuclear cell interstitial nephritis and iritis, presumably related to a viral-like illness. However, serologic results were negative for those viruses known to be associated with iritisjuveitis (Epstein-Barr virus, cytomegalovirus, herpes simplex virus, and rubella) and Toxoplasma. All cultures were sterile. She had no exposure to any medications or drugs except for a single aspirin tablet per day. The patient had no rashes, eosinophilia, or eosinophiluria. Systemic illnesses known to be associated with either uveitis or iritis [l-13] were not present by either clinical criteria or laboratory investigation. Despite her minimal cough, which resolved rapidly with steroids, the chest radiographic findings were normal. The diagnosis of sarcoidosis seemed unlikely. At no time was there mediastinal lymph node enlargement, hepatic dysfunction, or hypercalcemia. The negative tuberculin test result and the normal chest radiographic appearance militated against a diagnosis of tuberculosis. No evidence of any collagen vascular disease or vasculitis was noted on the initial evaluation or during the 24 months of close follow-up. There were no skin or mucous membrane lesions to suggest Behcet’s disease [6] or the StevensJohnson syndrome. Because of the article by Dobrin et al [ 131, bone marrow biopsy was performed to search for granulomas, but none was found. The patients previously described had eosinophilic interstitial nephritis, in contrast to our patient who had mononuclear cell interstitial infiltration. There was a dramatic response to prednisone treatment tapered to discontinuation over two months. In conclusion, it appears that our patient had acute mononuclear cell interstitial nephritis and iritis associated with a systemic disease. Response to steroid therapy was dramatic. Patients with this renal-ocular constellation may show significant response to a short-term course of steroids.
REFERENCES 1.
James DG: Uveitis is a systemic disorder (editorial). Am J Med
2.
1978; 65: 567-568. Schlaegel TF Jr, O’Connor GR: Tuberculosis and syphilis
3.
(letter). Arch Ophthalmol 1981; 99: 2206-2207. Perkins ES: Ocular sarcoidosis (editorial). Arch Ophthalmol
4.
190
1981; 99: 1193. Haynes BF, Fishman ML, Fauci AS, Wolff SM: The ocular manifestations of Wegener’s granulomatosis. Fifteen years
July 1984
The American Journal of Medlclne
Volume 77
experience and review of the literature. Am J Med 1977; 63: 131-141.
5.
O’Connor GR: Current concepts in ophthalmology. Uveitis and the immunolcgically compromised host N EnglJ Med 1978; 299: 130-132.
6.
Colvard DM, Robertson DM. O’Duffy JD: The ocular manifestations of Behcet’s disease. Arch Ophthalmol 1977; 95: 1813-1817.
ACUTE RENAL FAILURE AND IRITIS-STEINMAN
7. 8.
9.
10.
Ross WH, Sutton HF: Acquired syphilitic uveitis. Arch Ophthalmol 1980; 98: 498-498. Rao NA, Font RL: Toxoplasmic retinochoroiditis: electronmicroscopic and immunofluorescence studies of formalin-fixed tissue. Arch Ophthalmol 1977; 95: 273-277. Guignard JP, Torrado A: Interstitial nephritis and toxoplasmosis in a lo-vear-old child. J Pediatr 1974; 85: 38% 382. Sumers KD, Sugar J, Levine R: Endogenous dissemination of genital herpes virus hominis type 2 to the eye. Br J Ophthalmol 1980; 64: 770-772.
11.
12. 13.
and SILVA
Darougar S, John AC, Viswalingam M, Cornell L, Jones BR: Isolation of chlamydia psittaci from a patient with interstiiial keratitis and uveitis associated with otological and cardiovascular lesions. Br J Ophthalmol 1978; 62: 709714. Shields JA, Waring GD Ill, Monte LG: Ocular findings in leprosy. Am J Oohthalmol 1974; 77: 880-890. Dobrin RS; Vernier RL, Fish AL: Acute eosinophilic interstitial nephritis and renal failure with bone marrow-lymph node granulomas and anterior uveitis. A new syndrome. Am J Med 1975; 59: 325-333.
July 1994
The American Journal of Medlclne
Volume 77
191