Sulfasalazine therapy was discontinued 4 days later. No commercial re-use. 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.  MACarrigan Treatment with 60 mg/d of oral prednisolone was begun on the patient's ninth day at the hospital and tapered with improvement of clinical symptoms. Betamethasone therapy was discontinued while treatment with sulfasalazine was increased to 2 g/d. © BMJ Publishing Group Limited 2020. No serologic evidence of Epstein-Barr virus, cytomegalovirus, or other viral infections have been reported in hypersensitivity syndrome, although HHV-6 infection has not been specifically investigated. This is a delayed type IVb hypersensitivity syndrome that presents skin eruptions, fever, lymphadenopathy, hepatitis and hematological abnormalities like eosinophilia and atypical lymphocytes. Yoshikawa The clinical features of hypersensitivity syndrome are similar to those of infectious mononucleosis.  YKikuchi Carrigan Recently, a severe infectious mononucleosislike syndrome caused by HHV-6 infection was reported in immunocompetent adults.5-7 Clinical signs included high fever, skin rash, generalized lymphadenopathy, liver dysfunction, and leukocytosis with the appearance of atypical lymphocytes. Shear See rights and permissions. Reprints: Mikiko Tohyama, MD, Department of Dermatology, Ehime University School of Medicine, Shitsukawa, Shigenobucho, Onsengun, Ehime 791-0295, Japan (e-mail: tohm@m.ehime-u.ac.jp). 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.  KShiraki Han 1-4 The reaction, including fever, skin rash, lymphadenopathy, and internal organ involvement, usually occurs 2 to 5 weeks after initiating treatment with sulfasalazine. Abnormal laboratory findings included a white blood cell count of 23.6 × 109/L (20% atypical lymphocytes and 11% eosinophils). To confirm this observation, it must be further investigated in other patients. Human herpesvirus 6 has been identified as the cause of exanthem subitum.14 Most people are infected with HHV-6 in early childhood. Clipboard, Search History, and several other advanced features are temporarily unavailable. Yalcin Customize your JAMA Network experience by selecting one or more topics from the list below.  GMRathjen Pulmonary infiltration and eosinophilia associated with sulfasalazine therapy for ulcerative colitis: a case report and review of literature. The lavage specimen showed a … Okuno  GJune Treatment with all medications except ketotifen fumarate was discontinued. Sulfasalazine-induced hypersensitivity syndrome (SIHS) is a serious systemic delayed adverse drug reaction that is associated with significant morbidity and mortality.  et al. Treatment with 1.5 g/d of sulfasalazine and 1 mg/d of betamethasone suppository was commenced, and the patient's symptoms resolved 2 weeks later. Sulfasalazine has been reported to induce pulmonary eosinophilia and hypersensitivity with symptoms of dyspnea and fever. Yamakado S, Yoshida Y, Yamada T, Kishida T, Kobayashi M, Nomura T. Intern Med. However, PCR analysis is more sensitive, detecting HHV-6 DNA in 49% to 88% of PBMCs in healthy seropositive adults.19,20 A recent study suggested that the detection of HHV-6 DNA in serum by quantitative PCR defined the border between latency and active viral replication.21 In contrast, isolating the virus is the most reliable method of proving infection, because HHV-6 is rarely isolated from the PBMCs of healthy subjects.22 Our observations of the isolation of HHV-6 from PBMCs and the remarkable increase in anti–HHV-6 IgG titers without the appearance of IgM antibodies indicated reactivated HHV-6 infection.  NSchirmer Clinical signs included a maculopapular rash progressing to exfoliative erythroderma, fever, and lymphadenopathy.  KEizuru  RPSchloemann  NHSpielberg • In infants under 2 years of age.  RW Detection by PCR of HHV-6 and EBV DNA in blood and oropharynx of healthy adults and HIV-positives. Leukocytosis, atypical lymphocytes, liver dysfunction, and renal disturbance were also observed. Leukocytosis, atypical lymphocytes, liver dysfunction, and renal disturbance were also observed. A severe adverse reaction to sulfasalazine has been identified as a type of hypersensitivity syndrome.1-4 The reaction, including fever, skin rash, lymphadenopathy, and internal organ involvement, usually occurs 2 to 5 weeks after initiating treatment with sulfasalazine. Mauri-Hellweg et al27 have demonstrated drug-induced activation and proliferation of PBMCs in vitro in patients with hypersensitivity syndrome. It seems likely that the reactivation of HHV-6 is specific to hypersensitivity syndrome. Jarrett Azulfidine (sulfasalazine) is an anti-inflammatory medication used to treat mild to severe ulcerative colitis and rheumatoid arthritis. Patients with a known hypersensitivity to sulfasalazine, its metabolites or any of the excipients as well as sufonamides or salicylates.  MH Azulfidine-(sulfasalazine-) induced hepatic injury. Published by BMJ. Oral sulfasalazine inhibits the absorption and metabolism of folic acid and may cause folic acid deficiency, potentially resulting in serious blood disorders (e.g. Our website uses cookies to enhance your experience. 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. We suggest that HHV-6 infection may be a required cause of hypersensitivity syndrome. 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.  Y T-cell immune response to human herpesvirus-6 in healthy adults. If acute intolerance syndrome is suspected, promptly discontinue treatment with Asacol HD. These findings led us to hypothesize that severe drug-induced hypersensitivity syndromes have a 2-stage course: first, T-cell activation develops as an immune response to reactive drug metabolites and second, HHV-6 reactivated by activated T cells affects the general condition of the patients and causes infectious mononucleosislike symptoms. Treatment with 0.5 g/d of sulfasalazine was started after all medications except loxoprofen had been discontinued. DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) is a drug-induced hypersensitivity syndrome that can mimic malignant lymphoma. The patient was diagnosed as having hypersensitivity syndrome due to sulfasalazine use with multivisceral involvement. The expected product was 776 base pairs (bp). The antibody titers against HHV-7, Epstein-Barr virus, cytomegalovirus, measles, adenovirus, and toxoplasma were within normal ranges throughout the patient's clinical course. In this report, a case of sulfasalazine- induced DRESS syndrome (the acronym for Drug Rash with Eosinophilia and Systemic Symptoms) is described. Eosinophilia, atypical lymphocytosis, liver dysfunction, and renal disturbance are also frequently observed with this syndrome. David Sumiyoshi S Arch Dermatol. Okuno The patients showed similar clinical courses associated with reactivated HHV-6 infection. In this report, a case of sulfasalazine-induced DRESS syndrome (the acronym for Drug Rash with Eosinophilia and Systemic Symptoms) is described. worsening of these symptoms while on treatment. Results from a physical examination revealed a high fever (body temperature, 39.7°C), tonsillar pharyngitis, bilateral cervical lymphadenopathy, and hepatosplenomegaly. 4 The liver is most commonly affected in DRESS, presenting as acute hepatitis.  VRoujeau Cessation of sulfasalazine and administration of steroids led to dramatic improvement. 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. We are indebted to Mark R. Pittelkow, MD, for his helpful comments.  JAFerro Callot  et al. Sulfasalazine-induced hypersensitivity syndrome (SIHS) is a serious systemic delayed adverse drug reaction that is associated with significant morbidity and mortality. Keywords: Drug hypersensitivity, enzyme-linked immunospot assay, sulfasalazine Autoimmune disorders may also develop as a sequela of the condition. A severe adverse reaction to sulfasalazine therapy has been associated with hypersensitivity syndrome, the clinical features of which are similar to infectious mononucleosis.  RL Sulfasalazine toxic reactions. fasalazine hypersensitivity was proven by interferon-gamma A Case of Sulfasalazine-Induced Hypersensitivity Syndrome Confirmed by Enzyme-Linked Immunospot Assay Parkpoom Phatharacharukul,1 Jettanong Klaewsongkram2* 1Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Clinical signs include a maculopapular rash that often progresses to exfoliative erythroderma, fever, lymphadenopathy, and multivisceral involvement. 1998;134:1113-1117 ULFASALAZINE IS a common therapeuticdrugusedtotreat inflammatory bowel dis-ease, rheumatoid arthritis, 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. Systemic corticosteroid therapy generally improves the condition.  DAJosephs  |  Experimental infection of cynomolgus and African green monkeys with human herpesvirus 6. 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. Sobue Sulfasalazine should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.  SZAblashi Severe Hypersensitivity Syndrome Due to Sulfasalazine Associated With Reactivation of Human Herpesvirus 6. Privacy Policy| The investigation for infectious mononucleosis yielded negative results and a diagnosis of sulfasalazine-induced hypersensitivity syndrome was confirmed using enzyme-linked immunospot assays. A generalized maculopapular rash was observed over the patient's face, trunk, and extremities (Figure 1). Therefore, the adverse drug reaction causing hypersensitivity syndrome requires additional factors.  et al. Seroconversion to human herpesvirus 6 following liver transplantation is a marker of cytomegalovirus disease. We did not observe an increase in their anti–HHV-6 IgG titers throughout their clinical courses.  W Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity.  K Drug-induced pseudolymphoma and hypersensitivity syndrome. Sulfasalazine is contraindicated in patients with porphyria, urinary or intestinal obstruction, and hypersensitivity to sulfasalazine, its metabolites, sulfonamides, or salicylates. However, we determined that her anti–HHV-6 IgG titer had increased from 1:320 on the second hospital day to 1:2560 on the sixth hospital day when a preserved serum sample was examined. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Fulminant hepatitis in primary human herpesvirus-6 infection. Sotolongo One explanation for this finding might be that the corticosteroids suppressed an excessive immune response to drug metabolites and/or inhibited the production of cytokines caused by massive replicated viruses, which in turn induced severe illness. Clinical signs included a maculopapular rash progressing to exfoliative erythroderma, fever, and lymphadenopathy. 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. drugs and medicines; immunology; intensive care. Sulfasalazine is contraindicated in: Infants under the age of 2 years. DRESS typically develops three weeks to three months after starting treatment with the precipitating drug. doi:10.1001/archderm.134.9.1113, © 2020 American Medical Association. 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. Cessation of sulfasalazine We describe a previously unreported association of and administration of steroids led to dramatic improvement. It has also been used “off label” for Crohn's disease and ankylosing spondylitis. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome and the Rheumatologist. Sulfasalazine Sulfasalazine 2013-01-18 00:00:00 Reactions 723 - 17 Oct 1998 Hypersensitivity syndrome associated with reactivation of human herpesvirus 6: 2 case reports Sulfasalazine-induced hypersensitivity syndrome was associated with the reactivation of human herpesvirus 6 (HHV-6) in 2 patients. Get free access to newly published articles. 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. The clinical features of the syndrome appeared 18 and 32 days after administration of sulfasalazine. Common side effects of Azulfidine include gastrointestinal disturbances, headache, allergic reactions, rash when exposed to sunlight, and changes in skin or urine color. : 2 Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Allergy and Clinical Immunolgy Research Group, Chulalongkorn … In general, the appearance of anti–HHV-6 IgM antibodies suggests primary infection, while a remarkable increase in IgG titers without IgM antibodies indicates reactivated HHV-6 infection. Medications except loxoprofen had been on sulfasalazine for 2 months to treat mild to severe ulcerative colitis Crohn! We believe these cases represent hypersensitivity syndrome has occurred for some people who sulfasalazine. Mauri-Hellweg et al27 have demonstrated drug-induced sulfasalazine hypersensitivity syndrome and proliferation of PBMCs in vitro patients... 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