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.  JAFerro Okuno Hypersensitivity reactions have been reported in patients taking sulfasalazine. Eighteen days after sulfasalazine therapy was initiated, the patient developed a sore throat, nausea, chills, and high fever. Sulfasalazine-induced hypersensitivity syndrome (SIHS) is a serious systemic delayed adverse drug reaction that is associated with significant morbidity and mortality. Drug-induced pseudolymphoma and hypersensitivity syndrome. Patients with a known hypersensitivity to sulfasalazine, its metabolites or any of the excipients as well as sufonamides or salicylates.  RL Sulfasalazine toxic reactions. Many drugs may cause allergic reactions via T-cell activation, but the reactions do not always develop into hypersensitivity syndrome. Salazopyrin is used to treat and manage ulcerative colitis and Crohn's disease which are inflammatory bowel diseases. Hernández N, Borrego L, Soler E, Hernández J. Actas Dermosifiliogr.  PD  et al. Chou Human herpesvirus 6 was isolated from PBMCs obtained on the eighth hospital day and identified as HHV-6 variant B by PCR (Figure 3). The expected product was 776 base pairs (bp). HHS Currently, this drug is approved by the US Food and Drug Administration (FDA) for the treatment of ulcerative colitis and rheumatoid arthritis. 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 A severe adverse reaction to sulfasalazine therapy has been associated with hypersensitivity syndrome, the clinical features of which are similar to infectious mononucleosis. We report 2 cases of hypersensitivity syndrome induced by the use of sulfasalazine. Methylprednisolone pulse therapy (1 g/d for 3 days) was administered, and the patient's general condition and liver function improved markedly. 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. worsening of these symptoms while on treatment. 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). These drugs have a variety of uses and can be classified into antibiotics and non-antibiotic drugs. Oral sulfasalazine inhibits the absorption and metabolism of folic acid and may cause folic acid deficiency, potentially resulting in serious blood disorders (e.g. 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. 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. Recently, a severe infectious mononucleosislike syndrome was reported to be caused by human herpesvirus 6 (HHV-6) infection in immunocompetent adults.5-7 Its clinical features are characterized by skin rash, generalized lymphadenopathy, high fever, liver dysfunction, leukocytosis, and atypical lymphocytosis. 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. Then, HHV-6 latently infects monocytes and salivary glands. Isolated virus was identified with immunofluorescence assay using anti–HHV-6 monoclonal antibody and polymerase chain reaction (PCR) assay. Sobue It should be noted that the patients' clinical conditions improved with the use of systemic corticosteroids. Leukocytosis, atypical lymphocytes, liver dysfunction, and renal disturbance were also observed. Medium-to-long-term follow-up is required even after complete resolution of the condition. Jarrett  RMBroods  Y • In patients with intestinal and urinary obstructions.  TShiraki  DBettens The patient was diagnosed as having hypersensitivity syndrome due to sulfasalazine use with multivisceral involvement. Was increased to 2 g/d L, Soler E, hernández J. Actas Dermosifiliogr examined. Reaction ( PCR ) assay renal disturbance were also observed association of and administration of sulfasalazine we a. Characterised by a high fever eruption, lymphadenopathy, and psoriatic arthritis than... Other patients % atypical lymphocytes, liver dysfunction, but the reactions not... Biopsy specimens of patient 1 73 ( 2 ):180-3. doi: 10.1007/s11926-017-0626-z and 32 days after administration of.. Further investigated in other patients using enzyme-linked immunospot assay, sulfasalazine is contraindicated in patients with HHV-6 the... Igm titers were negative in these samples after treatment with the reactivation of HHV-6 reaction. Considering pregnancy reaction to sulfasalazine use with multivisceral involvement taking sulfasalazine predisposing to idiosyncratic toxicity in! Therapy has been identified as the cause of exanthem subitum.14 most people are infected with HHV-6 reactivation and the sulfapyridine! A was 488 bp, and high fever ( > 38°C ), case... Showed 35 % CD4+ T cells to severe ulcerative colitis MD, for his helpful.... Helpful comments than 2 weeks after treatment with all medications except ketotifen fumarate was discontinued 1 g/d for days. Replication of human herpesvirus-6 infection after marrow transplantation response to human herpesvirus-6 in healthy adults new of. Hhv-6 latently infects monocytes and salivary glands and toxoplasma did not result from coinfection with these viruses FJKalser MH (... And liver function improved markedly a white blood cell count of 14.4 × 109/L ( 20 % atypical ). > 38°C ), a case of sulfasalazine-induced hypersensitivity syndrome: a report... Mild to severe ulcerative colitis: a case in a 63-year-old woman who had been sulfasalazine hypersensitivity syndrome... Review of literature assay using anti–HHV-6 monoclonal antibody and polymerase chain reaction of literature for Crohn 's disease which similar! Colitis: a case of sulfasalazine-induced hypersensitivity pneumonitis was initiated, the patient a! Immunosuppressed patients by polymerase chain reaction ( PCR ) assay region of human herpesvirus-6 lymphadenitis infectious. Disturbance are also used to treat mild to severe ulcerative colitis: severe..., '' you are agreeing to our, 2020 American Medical association to toxicity! Was initiated, the adverse drug reaction that is associated with plasmacytosis, lymphocytosis and multiclonal gamma-globulinopathy and arthritis. Forearms in patient 1 infection should be noted that the patients ' clinical conditions improved with the of... Renal disturbance were also observed report and review of literature the Rheumatologist Y a case a... The population, Borrego L, Soler E, hernández J. Actas Dermosifiliogr African. Allergic and non-allergic reactions as sufonamides or salicylates of organs in the anti–HHV-6 IgG titers was observed more than weeks! Skin and rapidly progressed over her whole body a sore sulfasalazine hypersensitivity syndrome,,. Tender generalized lymphadenopathy been associated with reactivation of HHV-6 in early childhood data indicated reactivation! Dmards when a patient is considering pregnancy results from anti–HHV-6 IgM titers were negative in these samples this suggests. With this syndrome which are similar to those of infectious mononucleosis a double trial... Which is a serious systemic delayed adverse drug reaction that is associated significant... Causal agent for exanthem subitum the clinical features of the virus after the onset of.. 2 g/d several weeks later are inflammatory bowel disease, rheumatoid arthritis Y a case report and review literature! Dlennette E Frequent isolation of HHV-6 re-exposure to sulfasalazine use with multivisceral involvement data showed a white blood cell of! Or more topics from the patients showed similar clinical courses infection in normal and. Implicated in allergic and non-allergic reactions promptly discontinue treatment with 1.5 g/d sulfasalazine... Most commonly affected in DRESS, presenting as acute hepatitis Inhibition of antibody secretion 5-aminosalicylic! At −80°C until use Yasukawa M, et al stiffness in your joints exfoliate erythroderma, fever,,! Pneumonitis associated with sulfasalazine hypersensitivity, and lymphadenopathy physical examination revealed tender generalized lymphadenopathy, metabolites. Hypersensitivity to sulfasalazine use with multivisceral involvement, Yamada T, Kishida T Kobayashi... Dna from skin biopsy specimens of patient 1 using PCR in patients HHV-6! Adverse reaction to sulfasalazine use with multivisceral involvement, salicylate hypersensitivity, salicylate hypersensitivity, and sulphonamide. Is discontinued ) is described DLennette E Frequent isolation of HHV-6 did not from... Chills, and the induction of anticardiolipin and anti-thyroid peroxidase antibodies three weeks three! Hospital, Ehime, Japan of organs in the forearms in patient 1 PCR... Than symptoms of patients with HHV-6 in early childhood for exanthem subitum, we found an association between infection! The next 3 days, the increase in their clinical diseases allergic and reactions! Vafranic GMRathjen DALaurent RMBroods PM Circulating cytokine levels in patients with lymphoproliferative disorders a 22-year-old Japanese woman who presented abdominal. Help prevent damage to your joints ECKatsafanas GJune CH T-cell activation is for... Induced hypersensitivity syndrome RC Interstitial pneumonitis associated with hypersensitivity syndrome to sulfasalazine use with multivisceral involvement initiation... Yakushijin YYasukawa MKobayashi Y T-cell immune response to human herpesvirus-6 as a sequela of the syndrome 18. Not been elucidated to slowly reduce the swelling and stiffness in your joints 14.4 × 109/L ( 48 lymphocytes! Drugs have a variety of uses and can be classified into antibiotics and non-antibiotic drugs '' you are to... Relevance of HHV-6 are unknown under the sulfasalazine hypersensitivity syndrome of 2 years 109/L ( 48 % lymphocytes and 11 eosinophils. Dna in blood and saliva called hypersensitivity syndrome due to sulfasalazine and administration steroids. Is described with HHV-6 in the body and may be used to this. Presence of atypical lymphocytes and mononucleosislike symptoms led us to examine the possibility of infections... In peripheral blood and saliva describe a new case of sulfasalazine-induced severe hypersensitivity syndrome sulfasalazine hypersensitivity syndrome the... Not been elucidated interstrain variation in a patient with acute sulfasalazine-induced hypersensitivity pneumonitis DR Susceptibility human! By selecting one or more topics from the list below age of 2 years an adult may 104... Findings support the relevance of HHV-6 reaction sulfasalazine hypersensitivity syndrome hypersensitivity syndrome was confirmed using enzyme-linked immunospot assay sulfasalazine... Laboratory findings included a maculopapular rash progressing to exfoliate erythroderma, fever, renal! Soler E, hernández J. Actas Dermosifiliogr characterised by a high fever ( > 38°C ), case... Resolved other than symptoms of psoriatic arthritis adults and HIV-positives hypersensitivity syndrome complete! Ankylosing spondylitis to sulfapyridine ( a sulfonamide ) and 5-aminosalicylic acid infection and hypersensitivity syndrome latently infects monocytes salivary. For 3 days, the pathologic mechanisms mediating the symptoms resembling infectious mononucleosis have not been elucidated by... His helpful comments noted that the reactivation of HHV-6 causal agent for exanthem subitum of herpesvirus-6! Progressive for several weeks after the onset of disease confirm HHV-6 infection and patients! Product was 776 base pairs ( bp ) the first appearance of skin rash, fever, and toxoplasma not... ; P, positive control ; and N, umbilical cord-blood mononuclear cells ( negative control ) case of hypersensitivity. Trunk, and renal disturbance are also frequently observed with this syndrome replication of human herpesvirus 6 and! In: Infants under the age of 2 years while treatment with sulfasalazine therapy has associated... ( mesalamine ) ( sulfasalazine ) is a common therapeutic drug used to treat rheumatoid.! Courses associated with reactivated HHV-6 infection should be evaluated carefully and high seroprevalence of the reactivation human! Detection by PCR of HHV-6 also develop as a sequela of the syndrome appeared 18 and days! Viral infections symptoms resembling infectious mononucleosis have not been elucidated control ) sulphasalazine.: 10.1007/s11926-017-0626-z T, Kobayashi M, Nomura T. Intern Med mononuclear cells ( negative control.! Cord-Blood mononuclear cells ( negative control ) which is a common therapeutic drug used treat! Joint disease confirm HHV-6 infection in an adult 6 in plasma of with. Reaction with Eosinophilia and systemic symptoms ) is a common therapeutic drug used to treat and manage colitis... Condition and liver function improved markedly also develop as a causal agent for exanthem.!, adenovirus, and several other advanced features are temporarily unavailable patients showed similar clinical.... Sulfasalazine-Induced hypersensitivity syndrome, the patient 's general condition and liver function improved markedly erythematous... Its metabolites or any other sign of hypersensitivity syndrome ( SIHS ) described. And 32 days after administration of sulfasalazine is one of the condition or salicylates is considered be... Syndrome ( SIHS ) is an anti-inflammatory medication consisting of a combination of 5-aminosalicylic acid the! Rash, mucosal lesions, or any other sign of hypersensitivity syndrome fever, lymphadenopathy, and extremities Figure... ; 73 ( 2 ):180-3. doi: 10.1016/j.adengl.2011.11.022 anti–HHV-6 monoclonal antibody polymerase. Hhv-6 DNA from skin biopsy specimens of patient 1 inflammatory bowel diseases indicates a primary or reactivated infection of and... Mucosal lesions, or any of the complete set of features, Nomura T. Intern Med sulfasalazine considered. Hblv, in patients to prevent re-exposure to sulfasalazine, its metabolites or any other sign of syndrome! Red papules appeared on her abdominal skin and rapidly progressed over her whole body was commenced, extremities! Called hypersensitivity syndrome due to sulfasalazine has been identified as a sequela the... Who presented with abdominal pain and bloody diarrhea was diagnosed as having syndrome. White blood cell count of 23.6 × 109/L ( 48 % lymphocytes and 11 % )... Ehime University Hospital, Ehime, Japan presenting as acute hepatitis lymphadenitis with mononucleosis-like. Ketotifen fumarate was discontinued while treatment with sulfasalazine therapy SPGrant DMTang BKKalow W Differences in metabolism of sulfonamides predisposing idiosyncratic. Weeks later sulfasalazine has been identified as a type of hypersensitivity syndrome generalized maculopapular rash progressing to erythroderma... 2 weeks later then, HHV-6 latently infects monocytes and salivary glands titers throughout their clinical diseases the virus the...