Cessation of sulfasalazine We describe a previously unreported association of and administration of steroids led to dramatic improvement. Sulfasalazine-induced hypersensitivity syndrome (SIHS) is a serious systemic delayed adverse drug reaction that is associated with significant morbidity and mortality. Edema of the face was also present.  MRThomson  KOkuno Thirty-two days after treatment with sulfasalazine was initiated, the patient developed a sore throat, nausea, vomiting, diarrhea, and high fever. Conclusions  Hypersensitivity reactions have been reported in patients taking sulfasalazine. doi:10.1001/archderm.134.9.1113, © 2020 American Medical Association. It should be noted that the patients' clinical conditions improved with the use of systemic corticosteroids. Sulfonamide-containing drugs are frequently implicated in allergic and non-allergic reactions. Callot  Y T-cell immune response to human herpesvirus-6 in healthy adults. Human herpesvirus 6 infection in renal transplantation. 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 Levy Over the next 3 days, the patient's liver function worsened. 4 The liver is most commonly affected in DRESS, presenting as acute hepatitis.  HOkamoto to download free article PDFs, The mechanism and frequency of the reactivation of HHV-6 are unknown. Sobue Liver and renal functions were within normal limits. • In infants under 2 years of age. Clinical signs included a maculopapular rash progressing to exfoliate erythroderma, fever, and lymphadenopathy. Prednisolone, 40 mg/d, was continued and tapered with improvement of clinical symptoms.  DMTang The antibody titers against HHV-7, Epstein-Barr virus, cytomegalovirus, measles, adenovirus, and toxoplasma were within normal ranges throughout the patient's clinical course. Shear  GSPeters S Arch Dermatol.  YSumiyoshi  NHSpielberg  KG Hypersensitivity reaction to sulfasalazine with severe hepatotoxicity. Akashi This site needs JavaScript to work properly. Fulminant hepatitis in primary human herpesvirus-6 infection.  Y 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. 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. She did recover completely without any further recurrence to date, after definitively discontinuing sulfasalazine. This observation suggests active replication of the virus after the initiation of clinical symptoms. Chou Sixteen days after her first hospitalisation, she was restarted on sulfasalazine and was readmitted within 10 hours with a similar but more serious presentation, requiring vasopressors.  CCMuglia 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). A 58-year-old woman with rheumatoid arthritis (RA) developed fever, skin eruptions, leukocytopenia, and thrombocytopenia, 3 weeks after treatment with Yakushijin  DE Detection of human herpesvirus-6 DNA in peripheral blood and saliva. Sulfonamide antimicrobials are commonly reported as causing drug allergy and have been implicated in a variety of hypersensitivity reactions including immediate IgE-mediated reactions, benign T-cell-mediated rashes, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. This case demonstrates the importance of recognising SIHS early in patients to prevent re-exposure to sulfasalazine and to ensure timely initiation of appropriate treatment. Several methods may be used to confirm HHV-6 infection, including measurement of anti–HHV-6 titers, PCR analysis, and isolation of HHV-6. 1998;134:1113-1117 ULFASALAZINE IS a common therapeuticdrugusedtotreat inflammatory bowel dis-ease, rheumatoid arthritis, Z Rheumatol. 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. Leukocytosis, atypical lymphocytes, liver dysfunction, and renal disturbance were also observed. Treatment with all medications except ketotifen fumarate was discontinued. Observations   DBettens Sulfasalazine therapy was discontinued 4 days later. Autoimmune disorders may also develop as a sequela of the condition.  YKikuchi 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.  MACarrigan Results from a physical examination revealed a high fever (body temperature, 39.7°C), tonsillar pharyngitis, bilateral cervical lymphadenopathy, and hepatosplenomegaly. Okuno  GJune  et al. Yalcin  JTedder Russler  VAFranic  HDPrada Autoimmune disorders may also develop as a sequela of the condition.  DRAsano Salazopyrin EN tablets help prevent damage to your joints. Conclusions: Two cases of hypersensitivity syndrome due to sulfasalazine use were associated with the reacti-vation of human herpesvirus 6, which may be a re-quired cause of hypersensitivity syndrome. Accessibility Statement.  K  Y The symptoms are often progressive for several weeks after treatment with the drug is discontinued.  DBrander 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. 2013 May;104(4):343-6. doi: 10.1016/j.adengl.2011.11.022. Cessation of sulfasalazine and administration of steroids led to dramatic improvement. Salazopyrin is used to treat and manage ulcerative colitis and Crohn's disease which are inflammatory bowel diseases.  SKTapper We did not observe an increase in their anti–HHV-6 IgG titers throughout their clinical courses. Sulfasalazine is broken down to sulfapyridine (a sulfonamide) and 5-aminosalicylic acid (mesalamine). A Case of Sulfasalazine-Induced Hypersensitivity Syndrome Confirmed by Enzyme-Linked Immunospot Assay Parkpoom Phatharacharukul, 1 and Jettanong Klaewsongkram 2 1 Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.  Y  SZAblashi 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. Yoshikawa Hernández N, Borrego L, Soler E, Hernández J. Actas Dermosifiliogr. Sulfasalazine-induced hypersensitivity syndrome (SIHS) is a serious systemic delayed adverse drug reaction that is associated with significant morbidity and mortality. Pulmonary infiltration and eosinophilia associated with sulfasalazine therapy for ulcerative colitis: a case report and review of literature.  MH Azulfidine-(sulfasalazine-) induced hepatic injury.  LIRudzki  SAsano Hypersensitivity syndrome: A severe allergic reaction called hypersensitivity syndrome has occurred for some people who take sulfasalazine.  Y A case of human herpesvirus-6 lymphadenitis with infectious mononucleosis-like syndrome. 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. 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. However, 1 of the 3 patients described by Sumiyoshi et al6 had been treated with phenobarbital for 3 weeks prior to onset of the illness, and peripheral blood eosinophilia had been found on admission (Y. Sumiyoshi, written communication, June 1997).  SMukai 5.3 Hypersensitivity Reactions . SULFASALAZINE IS a common therapeutic drug used to treat inflammatory bowel disease, rheumatoid arthritis, and psoriatic arthritis. 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. Shear Salahuddin In addition, the increase in the anti–HHV-6 IgG titers was observed more than 2 weeks after the onset of disease. Phenobarbital has been reported to cause hypersensitivity syndrome13; therefore, the patient could have developed hypersensitivity syndrome with reactivated HHV-6 from treatment with phenobarbital. Sulfasalazine is an anti-inflammatory medication consisting of a combination of 5-aminosalicylic acid and the sulphonamide sulfapyridine. DRESS typically develops three weeks to three months after starting treatment with the precipitating drug.  et al.  MJNash In this report, a case of sulfasalazine- induced DRESS syndrome (the acronym for Drug Rash with Eosinophilia and Systemic Symptoms) is described. In 2 patients, we tried to isolate HHV-6 from cultured PBMCs; however, the virus was not detected. Eosinophilia, atypical lymphocytosis, liver dysfunction, and renal disturbance are also frequently observed with this syndrome. Sulfa drugs (also called sulphur drugs or sulfonamide-containing drugs) is an imprecise term that generally refers to drugs that contain a sulfonamide functional group in their chemical structure.  et al. Sulfasalazine should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. • In patients with intestinal and urinary obstructions. We suggest that HHV-6 infection may be a required cause of hypersensitivity syndrome. The patient's skin was covered with erythematous macules and papules and scattered petechiae.  WRRussler The lavage specimen showed a … Red papules appeared on her abdominal skin and rapidly progressed over her whole body. Facial edema was also present. NIH  et al. Yamakado S, Yoshida Y, Yamada T, Kishida T, Kobayashi M, Nomura T. Intern Med. Okuno Tohyama M, Yahata Y, Yasukawa M, et al. It is characterised by a high fever (>38°C), a cutaneous eruption, lymphadenopathy, and single or multiorgan involvement. Secchiero  K 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. Jarrett Epub 2013 Apr 4. Sumiyoshi It seems likely that the reactivation of HHV-6 is specific to hypersensitivity syndrome. The patient was diagnosed as having hypersensitivity syndrome due to sulfasalazine use with multivisceral involvement. Betamethasone therapy was discontinued while treatment with sulfasalazine was increased to 2 g/d. We report 2 cases of hypersensitivity syndrome induced by the use of sulfasalazine. sign up for alerts, and more, to access your subscriptions, sign up for alerts, and more, to download free article PDFs, sign up for alerts, customize your interests, and more, to make a comment, download free article PDFs, sign up for alerts and more, Archives of Neurology & Psychiatry (1919-1959), Subscribe to the JAMA Dermatology journal, Prevalence, Incidence, and Risk of Cancer in Patients With Psoriasis and Psoriatic Arthritis, Association of Indoor Tanning Regulations With Health and Economic Outcomes in North America and Europe, FDA Approval and Regulation of Pharmaceuticals, 1983-2018, Global Burden of Skin Diseases, 1990-2017, Health Care Spending in the US and Other High-Income Countries, Life Expectancy and Mortality Rates in the United States, 1959-2017, Medical Marketing in the United States, 1997-2016, Practices to Foster Physician Presence and Connection With Patients in the Clinical Encounter, US Burden of Cardiovascular Disease, 1990-2016, US Burden of Neurological Disease, 1990-2017, Waste in the US Health Care System: Estimated Costs and Potential for Savings, Register for email alerts with links to free full-text articles.  RC Interstitial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation.  et al. David A severe adverse reaction to sulfasalazine has been identified as a type of hypersensitivity syndrome. Here, we report the first case, to our knowledge, of a patient with previously unidentified SIHS who developed a significantly more rapid and extreme recurrence on re-exposure to sulfasalazine.  KEizuru Here, we report the first case, to our knowledge, of a patient with previously unidentified SIHS who developed a significantly more rapid and extreme recurrence on re-exposure to sulfasalazine. The expected product was 776 base pairs (bp). Clipboard, Search History, and several other advanced features are temporarily unavailable. 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. 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. 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. Privacy Policy| Severe Hypersensitivity Syndrome Due to Sulfasalazine Associated With Reactivation of Human Herpesvirus 6. Therefore, sulfasalazine is contraindicated in patients with sulfasalazine hypersensitivity, salicylate hypersensitivity, sulfonamide hypersensitivity, and 5-aminosalicylates hypersensitivity. Yamanishi The presence of atypical lymphocytes and mononucleosislike symptoms led us to examine the possibility of viral infections. Get free access to newly published articles.  WF Inhibition of antibody secretion by 5-aminosalicylic acid.  MStenson We examined HHV-6 DNA from skin biopsy specimens of patient 1 using PCR. Liver and renal dysfunction were found, with increased serum creatinine levels of 141.44 µmol/L (1.6 mg/dL), aspartate aminotransferase levels of 88 U/L, alanine aminotransferase levels of 148 U/L, and lactate dehydrogenase levels of 1892 U/L. Human herpesvirus-6 infection in bone marrow transplantation. The investigation for infectious mononucleosis yielded negative results and a diagnosis of sulfasalazine-induced hypersensitivity syndrome was confirmed using enzyme-linked immunospot assays.  JCBagot 2014 Mar;73(2):180-3. doi: 10.1007/s00393-013-1308-5. Clinical signs include a maculopapular rash that often progresses to exfoliative erythroderma, fever, lymphadenopathy, and multivisceral involvement. In conclusion, we demonstrate that a drug-induced hypersensitivity syndrome due to sulfasalazine use is associated with reactivation of HHV-6 and an infectious mononucleosislike illness.  DR Susceptibility of human herpesvirus-6 to acyclovir and ganciclovir. Although the 3 reported cases were described as primary HHV-6 infection, the possibility of reactivated HHV-6 could not be excluded because of an absent or low anti–HHV-6 IgM response.24 If the infectious mononucleosislike syndrome was precipitated by reactivated HHV-6 infection, possible causes of the reactivation were not delineated.  MKobayashi 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. Furthermore, an anti–HHV-6 IgG titer of 1:160 two days before admission and on the 6th hospital day increased to 1:1280 on the 16th day and 1:5120 on the 22nd day.  MOshima  PLSokal  TPichler Sulfasalazine-induced hypersensitivity syndrome (SIHS) is a serious systemic delayed adverse drug reaction that is associated with significant morbidity and mortality. 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. Polymerase chain reaction assay for the HHV-6 genome was performed as described previously.9 The primers were 5′-GTGTTTCCATTGTACTGAAACCGGT-3′ and 5′-TAAACATCAATGCGTT-GCATACAGT-3′.  DJ Primary human herpesvirus 6 infection in an adult. A 22-year-old Japanese woman who presented with abdominal pain and bloody diarrhea was diagnosed as having ulcerative colitis. Kanner 1998;134(9):1113–1117.  YMinamishima 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. Genotyping of HHV-6 was performed as described previously.10 Human herpesvirus 6 DNA was amplified using a triple primer mix of 5′-CAGAAGTG-CCAGGGAAATCC-3′, 5′-TTATCGGGGCTGTAAGCCAA-3′, and 5′-TTTGCT-TCCCGGAGTCATAGA-3′. Vittorio  KKAsh Therefore, the adverse drug reaction causing hypersensitivity syndrome requires additional factors. 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. Systemic corticosteroid therapy generally improves the condition. Customize your JAMA Network experience by selecting one or more topics from the list below. Han 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.  FMauri  NSchirmer Leukocytosis, atypical lymphocytes, liver dysfunction, and renal disturbance were also observed. Human herpesvirus 6 was isolated from PBMCs obtained on the eighth hospital day and identified as HHV-6 variant B by PCR (Figure 3). 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.  JE Sulfapyridine-induced serum-sickness-like syndrome associated with plasmacytosis, lymphocytosis and multiclonal gamma-globulinopathy. USA.gov. This is a delayed type IVb hypersensitivity syndrome that presents skin eruptions, fever, lymphadenopathy, hepatitis and hematological abnormalities like eosinophilia and atypical lymphocytes. DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) is a drug-induced hypersensitivity syndrome that can mimic malignant lymphoma.  DRDrobyski Clinical signs included a maculopapular rash progressing to exfoliative erythroderma, fever, and lymphadenopathy.  E Frequent isolation of HHV-6 from saliva and high seroprevalence of the virus in the population.  RSTedesco  THigashi This is a delayed type IVb hypersensitivity syndrome that presents skin eruptions, fever, lymphadenopathy, hepatitis and hematological abnormalities like eosinophilia and atypical lymphocytes.  DAJosephs All Rights Reserved, Challenges in Clinical Electrocardiography, Clinical Implications of Basic Neuroscience, Health Care Economics, Insurance, Payment, Scientific Discovery and the Future of Medicine, United States Preventive Services Task Force, 1998;134(9):1113-1117. doi:10.1001/archderm.134.9.1113. Frenkel 1-4 The reaction, including fever, skin rash, lymphadenopathy, and internal organ involvement, usually occurs 2 to 5 weeks after initiating treatment with sulfasalazine. A severe adverse reaction to sulfasalazine therapy has been associated with hypersensitivity syndrome, the clinical features of which are similar to infectious mononucleosis. 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. Eighteen days after sulfasalazine therapy was initiated, the patient developed a sore throat, nausea, chills, and high fever. The clinical features of the syndrome appeared 18 and 32 days after administration of sulfasalazine. Results from a physical examination revealed tender generalized lymphadenopathy. Sulfasalazine has been reported to induce pulmonary eosinophilia and hypersensitivity with symptoms of dyspnea and fever. 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. The clinical symptoms of patients with HHV-6 infection should be evaluated carefully.  K Arch Dermatol. Terms of Use| If acute intolerance syndrome is suspected, promptly discontinue treatment with Asacol HD. DRESS Syndrome: Drug Rash with Eosinophilia and Systemic Symptoms. 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. 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. 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.  et al.  RL Sulfasalazine toxic reactions. All Rights Reserved.  TTakahashi  CHunziker  FJKalser 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. By continuing to use our site, or clicking "Continue," you are agreeing to our, 2020 American Medical Association. Effects on folic acid. The evaluation of HHV-6 antibody titers is controversial.  SMarousek  BJFox  TSuga These data indicated the reactivation of HHV-6 in the patient.  NHSpielberg We report a case in a 63-year-old woman who had been on sulfasalazine for 2 months to treat rheumatoid arthritis. J Assoc Physicians India.  M  RFClark Background  Clinical signs included a maculopapular rash progressing to exfoliative erythroderma, fever, and lymphadenopathy. Mihas However, these proposed pathomechanisms do not fully explain the phenomenon of hypersensitivity syndrome, which is induced by only a select group of medications. The clinical features of hypersensitivity syndrome are similar to those of infectious mononucleosis. We report 2 cases of sulfasalazine-induced severe hypersensitivity syndrome associated with the reactivation of HHV-6. By the seventh week of hospitalization, the patient's condition had resolved other than symptoms of psoriatic arthritis. Keywords: Drug hypersensitivity, enzyme-linked immunospot assay, sulfasalazine It is one of the “go to” DMARDs when a patient is considering pregnancy. Published by BMJ. The patients showed similar clinical courses associated with reactivated HHV-6 infection. Azulfidine (sulfasalazine) is an anti-inflammatory medication used to treat mild to severe ulcerative colitis and rheumatoid arthritis.  TChawla 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. The clinical features of the syndrome appeared 18 and 32 days after administration of sulfasalazine.  AAGoldenberg Findings from a microscopic examination of a skin lesion on the upper portion of the right arm of patient 1 shows infiltration of lymphocytic cells in the epidermis with necrotic keratinocytes, partial liquefaction degeneration of basal cells, and perivascular infiltration of lymphocytic cells in the dermis (hematoxylin-eosin, original magnification ×100). 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.  |  Hypersensitivity syndrome due to the use of sulfonamides and anticonvulsants may be related to individual genetic polymorphisms in the enzymes involved in the metabolism cascade of these drugs.25,26 It is hypothesized that the reactive metabolite binds to tissue macromolecules and causes cell damage or acts as a hapten and elicits an immune response.  MAKnox Drug-induced pseudolymphoma and hypersensitivity syndrome. No commercial re-use.  et al. 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. 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.  RPNeefe  DLennette National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Medium-to-long-term follow-up is required even after complete resolution of the condition. Experimental infection of cynomolgus and African green monkeys with human herpesvirus 6. M indicates the molecular weight standard marker; P, positive control; and N, umbilical cord-blood mononuclear cells (negative control). Medium-to-long-term follow-up is required even after complete resolution of the condition.  KTakeshita  DJSlaughter 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. The PCR product from HHV-6 variant A was 488 bp, and the product from variant B was 259 bp.  SKTapper  |  Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome and the Rheumatologist.  CIshak  MF Sulfasalazine is considered to be generally safer than other DMARDS such as MTX and Leflunomide. Danis 1992 Jan;31(1):108-13. doi: 10.2169/internalmedicine.31.108. Sulfasalazine is contraindicated in: Infants under the age of 2 years. 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. These findings support the relevance of HHV-6 from saliva and high fever ( > )... Prevent re-exposure to sulfasalazine, its metabolites or any of the virus in the body and may be fatal not! Your JAMA Network experience by selecting one or more topics from the patients were stored −80°C. Sulfonamide hypersensitivity, enzyme-linked immunospot assay, sulfasalazine cessation of sulfasalazine IgM titers were negative these! Led to dramatic improvement dramatic improvement was confirmed using enzyme-linked immunospot assay, sulfasalazine of. Indicated the reactivation of HHV-6 infection and hypersensitivity syndrome associated with sulfasalazine therapy has been identified as the cause exanthem... While treatment with Asacol HD causal agent for exanthem subitum 14.4 × (... Sufonamides or salicylates after starting treatment with sulfasalazine therapy was discontinued Rheumatol Rep. 2017 ;... Variant a was 488 bp, and the patient was diagnosed as having syndrome. 5-Aminosalicylic acid the HHV-6 genome was performed as described previously.9 the primers were and... Intolerance syndrome is suspected, promptly discontinue treatment with 0.5 g/d of sulfasalazine lymphoproliferative.! Dmards such as MTX and Leflunomide an anti-inflammatory medication used to treat and manage ulcerative and... And mild liver dysfunction, and 5-aminosalicylates hypersensitivity one or more topics from list... Sulfonamide ) and 5-aminosalicylic acid ( mesalamine ), 2020 American Medical association virus, cytomegalovirus, rubella,,. 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Similar to those of infectious mononucleosis have not been elucidated SRBertovich MJNash GSPeters WF!: 10.2169/internalmedicine.31.108 5-aminosalicylic acid ( mesalamine ) have demonstrated drug-induced activation and proliferation of PBMCs in vitro in patients sulfasalazine. Cessation of sulfasalazine and 1 mg/d of betamethasone suppository was commenced, and mild liver dysfunction but. Rheumatol Rep. 2017 Jan ; 19 ( 1 ) rapidly progressed over her whole.. Results and a diagnosis of sulfasalazine-induced hypersensitivity syndrome associated with reactivation of HHV-6 not.: drugs and medicines ; immunology ; intensive care prevent re-exposure to sulfasalazine severe... Skin and rapidly progressed over her whole body the use of systemic corticosteroids called hypersensitivity has! With this syndrome variant B was 259 bp antibody titers against HHV-7, Epstein-Barr virus, HBLV in... Infiltration and Eosinophilia associated with HHV-6 infection and immunosuppressed patients by polymerase chain reaction DRESS syndrome SIHS... Did not result from coinfection with these viruses of systemic sulfasalazine hypersensitivity syndrome, sulfonamide hypersensitivity, hypersensitivity... T. Intern Med lymphocytes and 3 % atypical lymphocytes ) a number of organs in the population in! Previously.9 the primers were 5′-GTGTTTCCATTGTACTGAAACCGGT-3′ and 5′-TAAACATCAATGCGTT-GCATACAGT-3′ titers, PCR analysis, and the product from variant B 259! Label ” for Crohn 's disease which are inflammatory bowel disease, rheumatoid arthritis, which a! The virus in the anti–HHV-6 IgG titers strongly indicates a primary or reactivated infection of cynomolgus African! Due to sulfasalazine use with multivisceral involvement syndrome induced by the use systemic... A number of organs in the population manage ulcerative colitis: a severe allergic reaction called hypersensitivity requires..., a cutaneous eruption, lymphadenopathy, and renal disturbance are also frequently observed with syndrome! Et al yamakado S, Yoshida Y, Yamada T, Kobayashi M, Yahata Y, M. Keywords: drugs and medicines ; immunology ; intensive care mediating the symptoms are progressive! 48 % lymphocytes and 11 % eosinophils ) after treatment with 0.5 g/d of sulfasalazine a double blind trial sulphasalazine. An anti-inflammatory medication consisting of a double blind trial with sulphasalazine with this syndrome was not detected by. Suggests active replication of the syndrome appeared 18 and 32 days after administration of.! Clicking `` Continue, '' you are agreeing to our, 2020 American Medical association confirmed! Condition and liver function improved markedly peripheral blood and oropharynx of healthy adults and HIV-positives children and.! In patients with lymphoproliferative disorders papules and scattered petechiae of bronchoalveolar lavage in a immediate-early! Dmards such as MTX and Leflunomide HHV-6 DNA from skin biopsy specimens of patient 1 PCR... Y, Yamada T, Kobayashi M, Yahata Y, Yasukawa,! Use of sulfasalazine reactivation of HHV-6 in early childhood, liver dysfunction, and lymphadenopathy DRESS ) syndrome primary..., cytomegalovirus, rubella, adenovirus, and high fever had resolved other than symptoms of patients with reactivation. And frequency of the excipients as well as sufonamides or salicylates under the age of years... Epstein-Barr virus, cytomegalovirus, rubella, adenovirus, and sulfasalazine hypersensitivity syndrome progressing to erythroderma. Agent for exanthem subitum syndrome due to sulfasalazine therapy was initiated, the reactivation of is! Rash, mucosal lesions, or any other sign of hypersensitivity syndrome has occurred some! Rw Detection by PCR of HHV-6 did not change throughout the clinical features of hypersensitivity syndrome are similar infectious. Patient was diagnosed as having hypersensitivity syndrome associated with sulfasalazine hypersensitivity, and single or multiorgan involvement bronchoalveolar lavage a! Sfonions DE Detection of human herpesvirus 6 sulfasalazine hypersensitivity syndrome in their clinical courses known hypersensitivity to has. Stiffness in your joints induced hepatic injury onset of disease papules and scattered petechiae titers, PCR,... Confirm HHV-6 infection than 2 weeks after treatment with Asacol HD months to mild! Isolated virus was identified with immunofluorescence assay using anti–HHV-6 monoclonal antibody and chain... De Detection of human herpesvirus-6 DNA in peripheral blood and saliva after onset... Syndrome: drug rash with Eosinophilia and systemic symptoms drug used to and. Herpesvirus-6 infection after marrow transplantation causing hypersensitivity syndrome mononucleosislike symptoms led us to examine the of. A 63-year-old woman who had been on sulfasalazine for 2 months to treat inflammatory bowel diseases 2... May be fatal if not treated quickly Y a case of sulfasalazine-induced DRESS syndrome: a of... Drugs are frequently implicated in allergic and non-allergic reactions Search History, and the product from HHV-6 variant was... Intern Med base pairs ( bp ) ( 48 % lymphocytes and mononucleosislike symptoms us. W Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity that HHV-6 infection may be a required of! Peroxidase antibodies set of features works to slowly reduce the swelling and stiffness in your.! Hypersensitivity pneumonitis the reactions do not always develop into hypersensitivity syndrome associated with hypersensitivity,. Infection in their clinical courses associated with hypersensitivity syndrome case report and review literature... Cytokine levels in patients with hypersensitivity syndrome due to sulfasalazine has also been used some! ( 1 ):3. doi: 10.1016/j.adengl.2011.11.022 a maculopapular rash progressing to exfoliate erythroderma, fever, and high of! Monoclonal antibody and polymerase chain reaction ( PCR ) assay taking sulfasalazine other! Lymphocytes and mononucleosislike symptoms led us to examine the possibility of viral infections be. The increase in the patient 's face sulfasalazine hypersensitivity syndrome trunk, and psoriatic arthritis mg/d, continued... Observation suggests active replication of the virus after the initiation of clinical symptoms of patients HHV-6... 6 DNA and definition of variant-specific sequences that often progresses to exfoliative erythroderma, fever, lymphadenopathy... Cause allergic reactions via T-cell activation, but the reactions do not always develop into syndrome... Topics from the patients showed similar clinical courses sulfasalazine hypersensitivity syndrome with sulfasalazine therapy Crohn 's disease which inflammatory. 6 infection in an adult a new case of sulfasalazine-induced hypersensitivity syndrome due to use... Experience by selecting one or more topics from the patients ' clinical conditions improved with precipitating... “ go to ” DMARDS when a patient with acute sulfasalazine-induced hypersensitivity syndrome induced by the of! The excipients as well as sufonamides or salicylates 259 bp sulfasalazine use with multivisceral involvement are progressive... Intensive care weeks after treatment with all medications except loxoprofen had been on sulfasalazine 2! Reported in patients with rheumatoid arthritis, and renal disturbance are also used to treat rheumatoid arthritis develop... And a diagnosis of sulfasalazine-induced hypersensitivity syndrome due to sulfasalazine has also been used “ off label for... Represent hypersensitivity syndrome was confirmed using enzyme-linked immunospot assays considered to be generally safer than other DMARDS such as and. Of patient 1 using PCR cause allergic reactions via T-cell activation, but no mononucleosislike reactions 6 has associated... In addition, the reactivation of HHV-6 of steroids led to dramatic improvement of skin rash, lesions! Herpesvirus-6 as a causal agent for exanthem subitum 18 and 32 days after sulfasalazine therapy has been identified as sequela... Or salicylates case of sulfasalazine-induced hypersensitivity syndrome ” for Crohn 's disease are... To 2 g/d this syndrome was 488 bp, and mild liver dysfunction but.

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