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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2017  |  Volume : 28  |  Issue : 4  |  Page : 934-936
Acute renal failure secondary to drug-related crystalluria and/or drug reaction with eosinophilia and systemic symptom syndrome in a patient with metastatic lung cancer

1 Department of Nephrology, Faculty of Medicine, Cukurova University, Adana, Turkey
2 Department of Internal Medicine, Faculty of Medicine, Cukurova University, Adana, Turkey

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Date of Web Publication21-Jul-2017


Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity is a severe adverse drug-induced reaction. Aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, and some drugs, can induce DRESS. Atypical crystalluria can be seen in patients treated with amoxycillin or some drugs and can cause acute renal failure. We describe a 66-year-old man who presented fever and rash and acute renal failure three days after starting amoxycillin. He was also using phenytoin because of cerebral metastatic lung cancer. Investigation revealed eosinophilia and atypical crystalluria. The diagnosis of DRESS syndrome was made, amoxicillin was stopped, and dose of phenytoin was reduced. No systemic corticosteroid therapy was prescribed. Symptoms began to resolve within three to four days. The aim of this paper is to highlight the importance of microscopic examination of urine in a case with acute renal failure and skin lesions to suspect DRESS syndrome.

How to cite this article:
Paydas S, Balal M, Kocabas F, Ay N. Acute renal failure secondary to drug-related crystalluria and/or drug reaction with eosinophilia and systemic symptom syndrome in a patient with metastatic lung cancer. Saudi J Kidney Dis Transpl 2017;28:934-6

How to cite this URL:
Paydas S, Balal M, Kocabas F, Ay N. Acute renal failure secondary to drug-related crystalluria and/or drug reaction with eosinophilia and systemic symptom syndrome in a patient with metastatic lung cancer. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2021 Oct 18];28:934-6. Available from: https://www.sjkdt.org/text.asp?2017/28/4/934/211331

   Introduction Top

Drug reaction with eosinophilia and systemic symptom (DRESS) syndrome including a severe skin eruption, fever, hematologic abnormalities (eosinophilia or atypical lymphocytes), and internal organ involvement usually two to six weeks after the initiation of drug therapy is a severe adverse drug reaction.[1] Eosinophilia is not a constant clinical finding, and cutaneous and systemic signs are variable. The main culprit drugs are carbamazepine and allopurinol. Sulfa derivatives, antidepressants, nonsteroidal anti-inflammatory drugs, and antimicrobials can induce DRESS. Despite the discontinuation of the culprit drug, there is a possibility of persistence or aggravation of symptoms. It is important for emergency physicians to consider this entity in patients with severe rashes. Severe cases of DRESS often require aggressive treatment; however, current pharmacologic treatment options are limited.[2]

   Case Report Top

A sixty-six-year-old male heavy smoker patient admitted to nephrology clinic because of generalized skin eruption, fever, sore throat, and acute renal failure. Following usage of amoxicillin plus clavulanic acid one week ago, he developed generalized pruritic and hyperemic eruption. He was also using phenytoin sodium, levetiracetam, enoksoparin sodium. In his medical history, he had right hemiparesis secondary to cerebral metastasis. He was treated with gemcitabie for 12 days following radiotherapy one month ago for metastatic lung cancer. He had treated with antituberculosis drugs 40 years ago. Physical examination showed blood pressure 130/80 mm Hg, pulse 80 beat/min, temperature 37.8°C, generalized erythematous pruritic skin eruptions, and right hemiparesis. On admission, his laboratory values are as following: white blood cell (WBC) 9900/μL (4500–10,300), eosinophil 22.6% (0.9%–4%), hemoglobin 12.1 g/dL (13.6–17.2), hematocrit 34.7% (39.5–50.3), platelets 257,000/μL (156,000-373,000), glucose 120 mg/dL (70–105), aspartate amino-transferase 45 U/L (15–41), alanine amino-transferase 43 U/L (17–63), Ca 7.9 mg/dL (8.9–10.3), blood urea nitrogen 51 mg/dL (820), lactate dehydrogenase 300 U/L (115248), creatinine 2.49 mg/dL (0.7–1.2), sodium (Na) 135 mmol/L (132–144), potassium 4.2 mmol/L (3.6–5.1), phosphorus 3.2 mg/dL (2.4–4.7), procalcitonin 0.853 ng/dL (0–05), and C-reactive protein 14.7 mg/dL (0–0.8). On stick examination, urinary density was 1014, pH 5, protein positive, WBC 1, red blood cell (RBC) 2, amorphous phosphate-crystal negative, and amorphous urate crystals negative. Urine Na was 10 mEq/L. Urine micros-copic examination showed WBC 3–4, RBC 5–6, granular casts and large amount of crystalls per high power field. On peripheral blood smear, eosinophilia was detected and other cell series were found to be normal.

At first evaluation, we considered that the patient had DRESS syndrome. Although dermatologist recommended stopping of anticonvulsive drugs, we only reduced the dose of these drugs. Renal functions and skin lesions improved by the 4th hospital day, and he was discharged with clinical improvement.

   Discussion Top

The clinical findings of our patient were compatible drug rash with eosinophilia and systemic symptoms (DRESS) syndrome which is a rare drug reaction. Clinical findings such as fever, eruptions, eosinophilia, and involvement of organs all developed suddenly. Especially, aromatic anticonvulsive drugs such as in our patient and sulfonamides are most common causes of DRESS. However, a variety of other drugs such as allopurinol, mino-cycline, dapsone, sulfasalazine, and mexiletine and antiretrovirals have also been associated with DRESS. Cross-sensitivity is as high as 75% among the aromatic anticonvulsants.[3]

The diagnostic criteria of DRESS syndrome have been well described and consist of acute rash, fever (>38°C), lymphadenopathy at least in two different regions, at least one organ involvement and laboratory findings of eosinophilia, lymphocytosis, thrombocytopenia, and atypical lymphocytes. More than three findings are accepted as diagnostic. Our patient fulfilled these diagnostic criteria.

The pathogenesis of DRESS syndrome is only partially understood. Different mechanisms have been implicated in its development, including detoxification defects leading to reactive metabolite formation and subsequent immunological reactions resulting in slow acetylation and reactivation of dormant viruses, including Epstein–Barr virus and human herpesvirus (HHV)-6.[1],[4] The detection of HHV-6 reactivation has even been recently proposed as a diagnostic marker for DRESS. Some authors suggested that reactivation of HHV-6 was related to the activation of DRESS syndrome. Mortality is 10% in DRESS syndrome, especially in patients with eosinophilic infiltration in the liver. There is no curative therapy, and the potential drug has to be stopped immediately. We doubted amoxicillin plus clavulanic acid with or without anticonvulsive drugs caused the development of DRESS syndrome and stopping of amoxicillin plus clavulanic acid and also the dose reduction of phenytoin sodium and levetiracetam resulted in his improvement. Some authors reported that systemic corticosteroids and/or intravenous immune globulin improved the clinical symptoms in severe disease.[5] In patients with reactivation of HHV-6, steroids plus ganciclovir is recommended (the French Society of Dermatology published a report in 2010 outlining a consensus on therapeutic management of DRESS).[6] Because of potential properties of detoxification, N-acetylcysteine was also recommended. In literature, there are case reports that improved the clinic and laboratory values with high-dose N-acetyl cysteine in DRESS syndrome due to anticonvulsants.[7] However, it must be kept in mind that high-dose N-acetylcysteine can cause the angioedema.

Dermatological findings in our patient may represent immune complex syndromes related to drugs or infection. Malignancies and/or vasculitis can be other possibilities in our patient, but the improvement of clinical and laboratory values with only conservative measures supports the diagnosis of DRESS syndrome.

Detection of excessive crystals in his urine sediment was the important finding, and there were some risk factors in our patient for crystalluria such as high dose of drugs, relatively low urine pH and dehydration. Amoxicillin can be related to transient asymptomatic crystalluria and/or macroscopic hematuria without renal insufficiency and crystalluria with or without hematuria and renal insufficiency. The pathophysiology is not clearly understood, but it is supposed that renal insufficiency is related to precipitation of crystals in tubules and medullary congestion. We did not perform renal biopsy, but we consider that mild renal insufficiency seen in our patient was secondary to crystalluria. According to some authors after cessation of drug, crystalluria improves within 24 h, and hematuria and acute renal failure also improve in three and three to 17 days, respectively, as in our patient.[8]

In conclusion, we describe a case with acute renal failure secondary to amoxicillin-related crystalluria and/or DRESS syndrome and metastatic lung cancer. Besides amoxicillin, HHV, anticonvulsive drugs, or dehydration could have contributed to renal failure in our patient. While urinary examination through dipstick method may not warn clinician, microscopic examination of urine sediment provides essential clues for the diagnosis and one may reach surprising diagnosis.

Conflict of interest: None declared.

   References Top

Criado PR, Criado RF, Avancini JM, Santi CG. Drug reaction with Eosinophilia and Systemic Symptoms (DRESS)/Drug-induced Hypersensitivity Syndrome (DIHS): A review of current concepts. An Bras Dermatol 2012; 87:435-49.  Back to cited text no. 1
Ting TY. Anticonvulsant hypersensitivity syndrome: Identification and management. Curr Treat Options Neurol 2007;9:243-8.  Back to cited text no. 2
Wang XQ, Lang SY, Shi XB, Tian HJ, Wang RF, Yang F. Cross-reactivity of skin rashes with current antiepileptic drugs in Chinese population. Seizure 2010;19:562-6.  Back to cited text no. 3
Kano Y, Inaoka M, Shiohara T. Association between anticonvulsant hypersensitivity syndrome and human herpesvirus 6 reactivation and hypogammaglobulinemia. Arch Dermatol 2004;140:183-8.  Back to cited text no. 4
Kito Y, Ito T, Tokura Y, Hashizume H. High-dose intravenous immunoglobulin monotherapy for drug-induced hypersensitivity syndrome. Acta Derm Venereol 2012;92:100-1.  Back to cited text no. 5
Descamps V, Ben Saïd B, Sassolas B, et al. Management of drug reaction with eosinophilia and systemic symptoms (DRESS). Ann Dermatol Venereol 2010;137:703-8.  Back to cited text no. 6
Vélez A, Moreno JC. Toxic epidermal necrolysis treated with N-acetylcysteine. J Am Acad Dermatol 2002;46:469-70.  Back to cited text no. 7
van Noord C, Wulkan RW, van den Dorpel MA. Crystalluria. Neth J Med 2012;70:84, 87.  Back to cited text no. 8

Correspondence Address:
Saime Paydas
Department of Nephrology, Faculty of Medicine, Cukurova University, Adana 01330
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PMID: 28748902

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