A 46-year-old man comes to the office due to recurrent joint pain. The patient has had 3 gout flares during the past year and was prescribed allopurinol 2 months ago. He has had mild pain in multiple joints over the past week that feels different from prior gout attacks. He has also had malaise, nausea, and low-grade fevers. Medical history is otherwise significant for hypertension, for which he takes lisinopril. Temperature is 37.5 C (99.5 F), blood pressure is 128/84 mm Hg, and pulse is 68/min. Physical examination shows mild tenderness of small joints of the hands, elbows, and knees without edema or erythema. There is faint maculopapular rash on the extremities and trunk. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 13 g/dL |
| Platelets | 320,000/mm3 |
| Leukocytes | 8,200/mm3 |
| Neutrophils | 73% |
| Lymphocytes | 20% |
| Eosinophils | 7% |
| Serum chemistry | |
| Sodium | 140 mEq/L |
| Potassium | 4.4 mEq/L |
| Bicarbonate | 24 mEq/L |
| Blood urea nitrogen | 36 mg/dL |
| Creatinine | 2.2 mg/dL |
| Urinalysis | |
| Protein | 1+ |
| White blood cells (WBCs) | 20-30/hpf |
| Casts | WBC casts |
Laboratory studies were within normal limits 2 months ago. Which of the following is the most likely diagnosis in this patient?
Acute interstitial nephritis | |
Causes |
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Clinical features |
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Diagnosis |
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Management |
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*Medications account for ~75% of cases. **Classic triad is present in only ~10% of cases. CMV = cytomegalovirus; NSAID = nonsteroidal anti-inflammatory drug; PPI = proton pump inhibitor; RBC = red blood cell; SLE = systemic lupus erythematosus; WBC = white blood cell. | |
This patient has acute kidney injury (AKI); the peripheral eosinophilia and pyuria with white blood cell (WBC) casts are indicative of acute interstitial nephritis (AIN). AIN involves antigen hypersensitivity that causes inflammation within the renal interstitium and tubules that leads to tubular accumulation of WBCs (ie, pyuria). Tubular damage may also lead to mild proteinuria and hematuria.
Patients with AIN are often asymptomatic but may present with nonspecific systemic signs and symptoms, such as fever, malaise, polyarthralgia, and maculopapular rash. AIN is commonly caused by medications, including antibiotics, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors. Allopurinol, which was given to this patient 2 months ago, is also commonly implicated. AIN is typically diagnosed clinically without the need for a biopsy. Treatment is prompt discontinuation of the offending medication; glucocorticoids are used if the syndrome persists after drug discontinuation.
(Choice B) Acute urate nephropathy is characterized by precipitation of uric acid within the renal tubules, which can cause AKI. Unlike AIN, it is not a hypersensitivity response, and it typically occurs in patients with sudden hyperuricemia caused by rapid malignant cell lysis (eg, chemotherapy administration). Long-standing gout may lead to renal dysfunction due to chronic urate nephropathy, but a bland urine sediment (eg, no WBCs) is expected.
(Choice C) Drug-induced lupus commonly causes malaise, arthralgias, and/or rash (as in this patient). However, AKI is uncommon and is typically caused by glomerulonephritis (eg, red blood cell casts, significant proteinuria) rather than AIN.
(Choice D) A serum sickness–like reaction can occur in response to certain medications (eg, allopurinol) and typically manifests with skin rash and arthralgias; however, AKI and peripheral eosinophilia are not expected.
(Choice E) Stevens-Johnson syndrome (SJS), which can be caused by a number of medications, including allopurinol, can present with nonspecific systemic symptoms and skin rash. However, the characteristic rash involves vesicle formation and epidermal detachment (rather than faint and maculopapular, as in this patient). AKI due to SJS is usually prerenal in etiology (ie, due to fluid loss from the skin) with a bland urinalysis.
Educational objective:
Acute interstitial nephritis (AIN) is characterized by acute kidney injury with pyuria and often white blood cell casts in the urine. AIN can be caused by a number of medications (eg, allopurinol) and may be accompanied by nonspecific systemic signs and symptoms (eg, fever, malaise, polyarthralgias, skin rash).