NLM The patient is a 58-year-old woman with asymptomatic Crohn's disease who, 10 days after initiating sulfasalazine, developed fevers, diffuse rash, pancytopenia, hypotension and hepatitis without a definitive source of infection. The diagnosis is DRESS, also known as drug induced hypersensitivity syndrome. Other viral infections must be excluded, because coinfections with HHV-6 and other herpesviruses have been reported.23 The 2 patients in our study showed no increase in anti–HHV-7, anti-cytomegalovirus, and anti–Epstein-Barr virus IgG titers.  JTedder Systemic corticosteroid therapy generally improves the condition. Pulmonary infiltration and eosinophilia associated with sulfasalazine therapy for ulcerative colitis: a case report and review of literature. Salazopyrin is used to treat and manage ulcerative colitis and Crohn's disease which are inflammatory bowel diseases. We report 2 cases of sulfasalazine-induced severe hypersensitivity syndrome associated with the reactivation of HHV-6.  RFClark DRESS typically develops three weeks to three months after starting treatment with the precipitating drug.  DE Detection of human herpesvirus-6 DNA in peripheral blood and saliva.  TKazuhiro Betamethasone therapy was discontinued while treatment with sulfasalazine was increased to 2 g/d. Yamanishi  Y Sulfasalazine has been reported to induce pulmonary eosinophilia and hypersensitivity with symptoms of dyspnea and fever. Sotolongo Drug Hypersensitivity Syndrome, also known as Drug Rash with Eosinophilia and Systemic Symptoms is a severe adverse reaction characterized by clinical manifestations including fever, skin eruption, lymphoadenopathy, associated with eosinophilia, leukocytosis and multiple visceral involvement, with 10% of mortality due to development of multiple organ failure. Customize your JAMA Network experience by selecting one or more topics from the list below. 2015 May;63(5):78-9. Associated rash usually progressed to desquamation.  GI Analysis of interstrain variation in a putative immediate-early region of human herpesvirus 6 DNA and definition of variant-specific sequences. Sulfasalazine is contraindicated in patients with porphyria, urinary or intestinal obstruction, and hypersensitivity to sulfasalazine, its metabolites, sulfonamides, or salicylates. Experimental infection of cynomolgus and African green monkeys with human herpesvirus 6.  et al.  TTakahashi  DRDrobyski  WRRussler  MKobayashi  CCMuglia Published by BMJ.  ECKatsafanas Methods: PBMC from 2 patients with severe hypersensitivity syndrome to sulfasalazine, 3 patients with sulfamethoxazole allergy and 5 healthy donors were isolated and incubated with medium only (negative control), 2 concentrations (10, 100 μg/ml) of sulfapyridine, 2 concentrations (100, 200 μg/ml) of sulfamethoxazole, and tetanus toxoid (10 μg/ml) as a positive control. Mauri-Hellweg  |  DRESS Syndrome: Drug Rash with Eosinophilia and Systemic Symptoms.  THigashi It is one of the “go to” DMARDs when a patient is considering pregnancy. Danis Human herpesvirus 6 has been identified as the cause of exanthem subitum.14 Most people are infected with HHV-6 in early childhood. The clinical symptoms of patients with HHV-6 infection should be evaluated carefully. Leukocytosis, atypical lymphocytes, liver dysfunction, and renal disturbance were also observed. In 1 patient, human herpesvirus 6 variant B was isolated from peripheral blood mononuclear cells, and in both patients anti–human herpesvirus 6 IgG titers increased considerably. On the patient's third hospital day, 30 mg/d of oral prednisolone was readministered because of high fever (body temperature, 39.5°C), erythroderma, progressive facial edema, and increasing levels of aspartate aminotransferase and alanine aminotransferase. Liver and renal functions were within normal limits. The antibody titers against HHV-7, Epstein-Barr virus, cytomegalovirus, measles, adenovirus, and toxoplasma were within normal ranges throughout the patient's clinical course. Okuno  et al. pms-SULFASALAZINE and pms-SULFASALAZINE-E. C. (sulfasalazine) are contraindicated: • In patients with hypersensitivity to sulfasalazine, its metabolites, or any other component of the product (See Composition), sulfonamides, or salicylates. 1-4 The reaction, including fever, skin rash, lymphadenopathy, and internal organ involvement, usually occurs 2 to 5 weeks after initiating treatment with sulfasalazine. By the seventh week of hospitalization, the patient's condition had resolved other than symptoms of psoriatic arthritis.  BJFox  DMTang  NHSpielberg  MRThomson A severe adverse reaction to sulfasalazine therapy has been associated with hypersensitivity syndrome, the clinical features of which are similar to infectious mononucleosis. All Rights Reserved. We present the results of bronchoalveolar lavage in a patient with acute sulfasalazine-induced hypersensitivity pneumonitis.  MEizuru In 2 patients, we tried to isolate HHV-6 from cultured PBMCs; however, the virus was not detected.  KG Hypersensitivity reaction to sulfasalazine with severe hepatotoxicity.  JAFerro  FMauri  FJKalser  MOshima Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction. Laboratory data showed a white blood cell count of 14.4 × 109/L (48% lymphocytes and 3% atypical lymphocytes).  RW Detection by PCR of HHV-6 and EBV DNA in blood and oropharynx of healthy adults and HIV-positives. to download free article PDFs,  CIshak Hernández N, Borrego L, Soler E, Hernández J. Actas Dermosifiliogr. Human herpesvirus 6 was isolated from PBMCs obtained on the eighth hospital day and identified as HHV-6 variant B by PCR (Figure 3).  et al. Therefore, the adverse drug reaction causing hypersensitivity syndrome requires additional factors. A drug-associated hypersensitivity syndrome has been reported with administration of sulfasalazine, anticonvulsants, dapsone, allopurinol, and several other medications.1-4,12,13 Its clinical features resemble those of infectious mononucleosis and appear 2 to 5 weeks after administration of the drugs. Salazopyrin EN tablets help prevent damage to your joints. This case illustrates that the hemophagocytic syndrome associated with reactivation of EBV can occur as part of drug hypersensitivity reactions in RA patients taking sulfasalazine.  HDPrada  WF Inhibition of antibody secretion by 5-aminosalicylic acid. Over the next 3 days, the patient's liver function worsened. Several methods may be used to confirm HHV-6 infection, including measurement of anti–HHV-6 titers, PCR analysis, and isolation of HHV-6. The mechanism and frequency of the reactivation of HHV-6 are unknown.  DJ Primary human herpesvirus 6 infection in an adult. Seven days after the onset of the disease, sulfasalazine therapy was discontinued, and the patient was treated with 50 mg/d of oral prednisolone for 4 days.  TPichler Yamakado S, Yoshida Y, Yamada T, Kishida T, Kobayashi M, Nomura T. Intern Med. Common side effects of Azulfidine include gastrointestinal disturbances, headache, allergic reactions, rash when exposed to sunlight, and changes in skin or urine color.  et al. A severe adverse reaction to sulfasalazine has been identified as a type of hypersensitivity syndrome. Nevertheless, the patient developed a generalized eruption and was admitted to Ehime University Hospital, Ehime, Japan. Interestingly, it has been considered that the reactivation of HHV-6 from latently infected PBMCs requires T-cell activation.28 On investigation of 4 patients who developed adverse drug reactions but not hypersensitivity syndrome, an increase in anti–HHV-6 IgG titer was not found and the virus was not isolated.  et al.  PLSokal  K  RSHoness The DNA was detected from frozen skin specimens obtained on the patient's 19th hospital day, but not from paraffin-embedded skin specimens obtained on the 6th day. The patients showed similar clinical courses associated with reactivated HHV-6 infection. S Arch Dermatol. IgG antibody to HHV-6 was determined using the indirect immunofluorescent antibody assay described previously.11 Mononuclear cells infected with HHV-6 (HST strain) were used as a target antigen. Eighteen days after sulfasalazine therapy was initiated, the patient developed a sore throat, nausea, chills, and high fever. We report 2 cases of hypersensitivity syndrome induced by the use of sulfasalazine. We would like to suggest possible treatment with an antiviral drug such as ganciclovir for hypersensitivity syndrome, since our observations indicate that HHV-6 infection occurs in a late stage of hypersensitivity syndrome.31.  FGreenspan No serologic evidence of viral infections has been reported with this syndrome; however, human herpesvirus 6 infection has not been specifically investigated, which could cause an infectious mononucleosislike syndrome. Severe Hypersensitivity Syndrome Due to Sulfasalazine Associated With Reactivation of Human Herpesvirus 6. Get the latest public health information from CDC:, Get the latest research information from NIH:, Find NCBI SARS-CoV-2 literature, sequence, and clinical content:  VRoujeau Clinical signs included a maculopapular rash progressing to exfoliate erythroderma, fever, and lymphadenopathy. We describe a new case of sulfasalazine-induced hypersensitivity syndrome associated with HHV-6 reactivation and the induction of anticardiolipin and anti-thyroid peroxidase antibodies. We describe 2 patients who experienced the sudden onset of severe infectious mononucleosislike illness 18 and 32 days after the initiation of therapy with sulfasalazine. Shear  DLennette Severe, lifethreatening, systemic hypersensitivity reactions such as drug rash with - eosinophilia and systemic symptoms (DRESS) have been reported in patients taking various drugs including sulfasalazine.  K Privacy Policy| Autoimmune disorders may also develop as a sequela of the condition. From the Department of Dermatology (Drs Tohyama, Yahata, and Hashimoto) and the First Department of Internal Medicine (Dr Yasukawa), Ehime University School of Medicine, Ehime, the Department of Microbiology, Osaka University Medical School, Osaka (Drs Inagi and Yamanishi), and the Department of Dermatology, Tokushima University School of Medicine, Tokushima (Dr Urano), Japan. Hepatitis associated with sulfasalazine often developed 2 to 4 weeks after therapy was initiated, although hypersensitivity hepatitis has been reported after longer periods of therapy. The clinical features of the syndrome appeared 18 and 32 days after administration of sulfasalazine.  RC Interstitial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation. 2014 Mar;73(2):180-3. doi: 10.1007/s00393-013-1308-5.  NSchirmer : 2 Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Allergy and Clinical Immunolgy Research Group, Chulalongkorn … A 29-year-old Japanese man with an 8-year history of psoriatic arthritis had been treated with numerous agents, including loxoprofen, cyclosporine, and prednisolone, which moderately controlled the disease.  et al. Two cases of hypersensitivity syndrome due to sulfasalazine use were associated with the reactivation of human herpesvirus 6, which may be a required cause of hypersensitivity syndrome.  YKikuchi Sulfasalazine has been reported to modulate the immune response by inhibiting the secretion of IgA and the production of interleukin 1 and tumor necrosis factor α.29,30 These effects of sulfasalazine on the immune system may facilitate the reactivation of HHV-6 by activated T cells and induce the constellation of symptoms and signs of hypersensitivity syndrome.  KEizuru  MJNash To exclude the possibility that the adverse drug reaction was nonspecifically associated with HHV-6 reactivation, we investigated 4 patients who developed adverse drug reactions due to oral administration of phenytoin, allopurinol, and acetaminophen.  RPNeefe  YSumiyoshi Secchiero We report 2 cases of hypersensitivity syndrome induced by the use of sulfasalazine.  Y T-cell immune response to human herpesvirus-6 in healthy adults.  SP Anticonvulsant hypersensitivity syndrome. 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