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In This Article
 »  Abstract
 » Introduction
 » Case Report
 »  References
 »  Article Figures

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DRUG WATCH
Year : 2012  |  Volume : 44  |  Issue : 3  |  Page : 412-414
 

Allopurinol-induced DRESS syndrome


1 Department of Internal Medicine, Sakarya University Faculty of Medicine, Sakarya, Turkey
2 Department of Gastroenterology, Sakarya University Faculty of Medicine, Sakarya, Turkey

Date of Submission30-Nov-2011
Date of Decision27-Jan-2012
Date of Acceptance28-Feb-2012
Date of Web Publication17-May-2012

Correspondence Address:
Selcuk Yaylaci
Department of Internal Medicine, Sakarya University Faculty of Medicine, Sakarya
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.96351

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 » Abstract 

A 70-year-old man was admitted to our clinic with complaints of fever, jaundice, dyspnea, and generalized rash after 3 months of allopurinol treatment for gout. On physical examination, he was found to have fever (38.5°C), jaundice, and generalized maculopapular rash. Leukocytosis, eosinophilia, elevation of liver enzymes, and hyperbilirubinemia were detected in his blood analysis. Skin biopsy was consistent with drug-induced hypersensitivity. He was diagnosed as Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). Allopurinol treatment was stopped and steroid treatment was launched. At day 24 of admission, the patient died because of multiple organ failure.


Keywords: Allopurinol, DRESS syndrome, gout, skin biopsy


How to cite this article:
Yaylaci S, Demir MV, Temiz T, Tamer A, Uslan MI. Allopurinol-induced DRESS syndrome. Indian J Pharmacol 2012;44:412-4

How to cite this URL:
Yaylaci S, Demir MV, Temiz T, Tamer A, Uslan MI. Allopurinol-induced DRESS syndrome. Indian J Pharmacol [serial online] 2012 [cited 2018 Dec 18];44:412-4. Available from: http://www.ijp-online.com/text.asp?2012/44/3/412/96351



 » Introduction Top


Allopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout. [1] The Drug Rash with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. It is a syndrome, caused by exposure to certain medications that may cause a rash, fever, inflamation of internal organs, lymphadenopathy, and characteristic hematologic abnormalities such as eosinophilia, thrombocytopenia, and atypical lymphocytosis.Allopurinol can cause DRESS syndrome in 2-6 weeks after allopurinol therapy. [2],[3],[4] In this text, we present a patient with complaints of fever, jaundice, dyspnea, and generalized rash after 3 months of allopurinol treatment for gout.


 » Case Report Top


A 70-year-old man was admitted to another hospital with arthralgia and was diagnosed as gout; thus, he was prescribed allopurinol treatment. He was admitted to our clinic with complaints of fever, jaundice, dyspnea, and generalized rash after 3 months of allopurinol treatment for gout [Figure 1]. The patient had chronic renal failure and hypertension. There was no history of asthma or rash, nor any known allergies. Family history was unremarkable. Physical examination detected fever (38.5°C), jaundice, diffuse erythema and maculo-papular rash all over the body. Analysis of blood revealed the following: Hemoglobin, 10.1 g/dl; WBC, 19000/mm 3 ; platelet, 326000/mm 3 ; eosinophil, 7300/mm 3 ; Alanine Transaminase (ALT), 429 IU/L; Aspartate Aminotransferase (AST), 369 IU/L; Gamma-Glutamyl Transpeptidase (GGT), 481 IU/L; Alkaline Phosphatase (ALP), 773 IU/L; Lactate Dehydrogenase (LDH), 721 IU/L; urea, 76 mg/dl; creatinine, 2.1 mg/dl; uric acid, 4 mg/ dl; International Normalized Ratio (INR), 1.4; total bilirubin, 16.9 mg/dl; direct bilirubin, 8 mg/dl; and IgE, 574 IU/ ml. No immature eosinophils were observed in the peripheral blood smear. Complete urinalysis was normal. Blood and urine cultures were sterile. Hepatitis B Surface Antigen (HBsAg), IgM Antibody to Hepatitis B Core Antigen (anti-HBcIgM), Antibody to Hepatitis C Virus (anti-HCV), IgM antibody for Hepatitis A Virus (anti-HAV IgM), Anti-Cytomegalovirus IgM Antibody (anti-CMV IgM), and anti-toxoplasma IgM were negative.  Brucella More Details agglutination test showed negative result. Anti-Nuclear Antibodies (ANA), Anti-Mitochondria Antibody (AMA), and Anti-Smooth Muscle Antibody (SMA) were negative. Abdominal ultrasonography showed a normal liver size, grade-2 hepatosteatosis and sludge in the lumen of the gallbladder. Endoscopic Retrograde Cholangiopancreatography (ERCP) was performed to rule out mechanical icterus and was found normal. Transthoracic echocardiography showed normal left ventricular systolic function and ejection fraction was 67%. Skin biopsy was consistent with the clinical suspicion of drug-induced hypersensitivity. The case was diagnosed as DRESS syndrome. Allopurinol was stopped and steroid treatment initiated. Urea, creatinine, and liver enzymes were gradually elevated during the follow-up. Acute renal failure and acute liver failure were detected. Hemodialysis was performed for renal failure. Clinical status of the patient was gradually deteriorated. On day 24 of admission, the patient died because of DRESS.
Figure 1: Rash after 3 months of allopurinol treatment for gout

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Prevelance of hyperuricemia is 5%. Allopurinol is efficacious and safe in most patients, but intolerance is estimated to occur in up to 10% of treated patients. Severe or life-threatening allopurinol Adverse Reactions (AE) occur less frequently. [1],[3],[4],[5]

DRESS syndrome is a severe adverse drug-induced reaction. It is a syndrome, caused by exposure to certain medications, which may cause a rash, fever, inflammation of internal organs, lymphadenopathy, and characteristic hematologic abnormalities such as eosinophilia, thrombocytopenia, and atypical lymphocytosis. DRESS is an acute, severe, and life-threatening disease, whose clinical presentation is unlike that of common drug hypersensitivity reactions. It involves multiorgan failure as a result of conditions such as nephritis, hepatitis, and encephalitis. Liver involvement and eosinophilia generally begin 2-6 weeks after the first drug is administered, that is, later than the skin reactions. Peripheral eosinophilia is a common finding in DRESS. Rash and hepatitis may persist for several weeks after the drug is discontinued and may be life-threatening. Diagnosisis based on clinical and laboratory findings. [2],[4],[5],[6]

The most common drugs known to cause DRESS syndrome are phenytoin, phenobarbital and carbamazepine. Allopurinol, sulphasalazine, nevirapine, and penicillamine are other such drugs. [2],[3],[5],[6] In a study of 38 patients with DRESS syndrome, all opurinol was found to be responsible for 5.3% of the cases. [7]

The pathogenesis of DRESS syndrome is not fully understood. Although the pathophysiology is still unknown, different factors have been postulated in DRESS syndrome's etiology. Immunological factors, genetic factors, and human herpes virus-type 6 are also implicated. A possible mechanism may be allopurinol or oxipurinol (major metabolite of allopurinol) hypersensitivity, and immune complex storage, which may result in vasculitis. Immunological factors, genetic factors, and Human Herpes Virus-type 6 are also implicated. [8],[9],[10]

There is no standard treatment of DRESS syndrome. The first step in treatment is discontinuation of the suspected drugs. High-dose corticosteroids can provide a dramatic improvement in clinical condition. [2],[3],[5],[7] Early cessation of the drug implicated in the development of DRESS syndrome will result in a better outcome. The DRESS syndrome can cause life-threatening multi-organ failure. [11],[12],[13],[14] The syndrome has a mortality rate of 10%. [5]

The patient in this case was admitted to our clinic with complaints of fever, jaundice, dyspnea, and generalized rash after 3 months of allopurinol treatment for gout. Leukocytosis, eosinophilia, elevation of liver enzymes, and hyperbilirubinemia were detected. Blood and urine cultures were sterile. HBsAg, anti-HBcIgM, anti-HCV, anti-HAV IgM, anti-CMV IgM, and anti-toxoplasma IgM were negative. Brucella agglutination test was negative. The ANA, AMA, and SMA were negative. ERCP was normal. Transthoracic echocardiography showed normal left ventricular systolic function and ejection fraction was 67%. The absence of immature eosinophils in the peripheral blood smear makes the diagnosis of eosinophilic leukemia unlikely. Other factors of renal failure and hepatitis (autoimmunity, infections, congestive heart failure, mechanical icterus) were ruled out. Skin biopsy was consistent with drug-induced hypersensitivity. DRESS syndrome was diagnosed with these clinical and laboratory findings. Thereafter, allopurinol treatment was stopped and steroid treatment was initiated. Urea, creatinine and liver enzymes were gradually elevated during the follow-up. Acute renal failure and transaminitis were detected. Hemodialysis was performed for the treatment of renal failure. Clinical status of the patient gradually deteriorated and on the 24 th day of admission, he died because of DRESS multiple organ failure.

The DRESS syndrome is a severe adverse drug reaction and has high mortality rates. It warrants initiation of an early treatment. Drug use must be investigated in patients with complaints of fever, jaundice, generalized rash, acute renal failure, and acute liver failure in order to rule out the possibility of DRESS syndrome.

Furthermore, judicious use of allopurinol may decrease the incidence and morbidity caused by this syndrome.

 
 » References Top

1.Terkeltaub RA. Clinical practice. Gout. N Engl J Med 2003;349:1647-55.  Back to cited text no. 1
    
2.Kumari R, Timshina DK, Thappa DM. Drug hypersensitivity syndrome. Indian J Dermatol Venereol Leprol 2011;77:7-15.  Back to cited text no. 2
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3.Tas S, Simonart T. Management of drug rash with eosinophilia and systemic symptoms (DRESS syndrome): An update. Dermatology 2003;206:353-6.  Back to cited text no. 3
    
4.Lee HY, Ariyasinghe JT, Thirumoorthy T. Allopurinol hypersensitivity syndrome: A preventable severe cutaneous adverse reaction? Singapore Med J 2008;49:384-7.  Back to cited text no. 4
    
5.Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, Finzi L, et al. The DRESS syndrome: A literature review. Am J Med 2011;124:588-97.  Back to cited text no. 5
    
6.Markel A. Allopurinol-induced DRESS syndrome. Isr Med Assoc J 2005;7:656-60.  Back to cited text no. 6
    
7.Um SJ, Lee SK, Kim YH, Kim KH, Son CH, Roh MS, et al. Clinical features of drug-induced hypersensitivity syndrome in 38 patients. J Investig Allergol Clin Immunol 2010;20:556-62.  Back to cited text no. 7
    
8.Sullivan JR, Shear NH. The drug hypersensitivity syndrome: What is the pathogenesis? Arch Dermatol 2001;137:357-64.  Back to cited text no. 8
    
9.Hashimoto K, Yasukawa M, Tohyama M. Human herpes virus 6 and drug allergy. Curr Opin Allergy Clin Immunol 2003;3:255-60.  Back to cited text no. 9
    
10.Bohan KH, Mansuri TF, Wilson NM. Anticonvulsant hypersensitivity syndrome implications for pharmaceutical care. Pharmacotherapy 2007;27:1425-39.  Back to cited text no. 10
    
11.Arellano F, Sacristan JA. Allopurinol hypersensitivity syndrome: A review. Ann Pharmacother 1993;27:337-43.  Back to cited text no. 11
    
12.Gutiérrez-Macías A, Lizarralde-Palacios E, Martínez-Odriozola P, Miguel-De la Villa F. Fatalallopurinol hypersensitivity syndrome after treatment of asymptomatic hyperuricaemia. BMJ 2005;331:623-4.  Back to cited text no. 12
    
13.Gyotoku E, Iwamoto T, Ochi M. A fatal case of drug-induced hypersensitivity syndrome due to allopurinol. Arerugi 2009;58:560-6.  Back to cited text no. 13
    
14.Eshki M, Allanore L, Musette P, Milpied B, Grange A, Guillaume JC, et al. Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: A cause of unpredictable multiple organ failure. Arch Dermatol 2009;145:67-72.  Back to cited text no. 14
    


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