Dapsone Hypersensitivity Syndrome Research Articles

#823 Effect of dapsone on the treatment of refractory IgA vasculitis

Abstract Background and Aims IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is a systemic IgA-mediated vasculitis of the small vessels commonly seen in children. The natural history of IgAV is generally self-limiting. However, one-third of patients experience symptom recurrence and a refractory course. We performed this study to examine the use of dapsone (4,4'-sulfonyldianiline or diaminodiphenyl sulfone) in refractory IgAV cases. Method A literature search of PubMed databases retrieved 16 articles published until May 31, 2023. A total of 38 patients with IgAV were recruited. Results A palpable purpura persisted in nearly all the patients with refractory course, followed by joint pain (25 of 38 patients; 69.2%). Hematuria and proteinuria were noted in 11 (28.9%) and 7 (18.4%) of the patients, respectively. Treatment response within 1-2 days was obtained in 12 of 38 patients (31.6%), compared to within ≥3 days in 22 patients (57.9%). Relapse after treatment discontinuation was reported in 21 patients (55.3%) but not in 11 patients (28.9 %). Twelve of the 38 patients (31.6%) reported adverse effects of dapsone, including arthralgia (5.3%), rash (5.3%), dapsone hypersensitivity syndrome (2.6%), methemoglobinemia (21%), and hemolysis (15.8%). These findings indicate that dapsone may have a beneficial effect on refractory IgAV. Conclusion It is observed that in spite of several adverse effects, dapsone treatment exerts a beneficial effect in IgAV patients with prolonged cutaneous manifestation refractory to corticosteroid. Close renal monitoring may be needed to discover renal involvement of IgAV. Multicenter randomized placebo-controlled trials are necessary to determine the standard dosage of dapsone at initial or tapering of treatment in IgAV patients.

Sulfone Syndrome: A Unique Delayed Type of Drug Hypersensitivity from Dapsone

Nowadays, dapsone is more commonly used in some dermatologic and inflammatory conditions other than leprosy. Even though it has excellent therapeutic efficacy, its side effects are of common concern. Although immune mediated drug hypersensitivity is less common, it can be fatal. Sulfone syndrome is a unique presentation that occurs in dapsone hypersensitivity syndrome (DHR). Here, we report on a 22-year-old female who was prescribed one month of dapsone for dermatitis. She developed a generalized maculopapular rash and low-grade fever and observed that her sclera had a yellowish discoloration. This case report demonstrates a unique character of delay-type drug hypersensitivity from dapsone, with the aim of increasing physician awareness when prescribing dapsone.

Development of an ARMS multiplex real-time PCR assay for the detection of HLA-B*13:01 genotype by detecting highly specific SNPs.

HLA-B*13:01 was strongly associated with Dapsone Hypersensitivity Syndrome (DHS). This study aimed to develop and validate a rapid and economical method for HLA-B*13:01 genotyping. Two tubes multiplex real-time PCR detection system comprising amplification refractory mutation system primers and TaqMan probes was established for HLA-B*13:01 genotyping. Sequence-based typing was applied to validate the accuracy of the assay. The accuracy of the assay was 100% for HLA-B*13:01 genotyping. The detection limit of the new method was 0.025 ng DNA. The positive rate of HLA-B*13:01 in the Bouyei (20%, n = 50) populations was significantly higher than that in the Uighur population (4%, n = 100), Han (4.5%, n = 200), and Tibetan (1%, n = 100) ( P < 0.05). The proposed method is rapid and reliable for HLA-B*13:01 screening in a clinical setting.

Overview and Current Advances in Dapsone Hypersensitivity Syndrome.

As a sulfone antibacterial agent, dapsone has been widely used to treat leprosy. Moreover, dapsone is also used in many immune diseases such as herpetic dermatitis because of its anti-inflammatory and immunomodulatory effects. However, dapsone can cause several adverse effects, the most serious being dapsone hypersensitivity syndrome. Dapsone hypersensitivity syndrome is characterized by a triad of eruptions, fever, and organ involvement, which limits the application of dapsone to some extent. In this article, we review current research about the interaction model between HLA-B*13:01, dapsone, and specific TCR in dapsone-induced drug hypersensitivity. In addition to the proposed mechanisms, we also discussed clinical features, treatment progress, prevalence, and prevention of dapsone hypersensitivity syndrome. These studies reveal the pathogenesis, clinical features, and prevalence from the perspectives of genetic susceptibility and innate and adaptive immunity in dapsone hypersensitivity syndrome, thereby guiding clinicians on how to diagnose, prevent, and treat dapsone hypersensitivity syndrome.

Dapsone hypersensitivity syndrome.

Dapsone hypersensitivity syndrome.

TAP2 Drives HLA-B∗13:01‒Linked Dapsone Hypersensitivity Syndrome Tolerance and Reactivity

Dapsone hypersensitivity syndrome (DHS) is restricted to HLA-B∗13:01. However, the positive predictive value for HLA-B∗13:01 is only 7.8%. To explore the potential coexisting factors involved in the occurrence of DHS, we carried out a GWAS and a genome-wide DNA methylation profile analysis comparing patients with DHS with dapsone-tolerant control subjects (all carrying HLA-B∗13:01). No non-HLA SNPs associated with DHS were identified at the genome-wide level. However, the pathway of antigen processing and presentation was enriched in patients with DHS, and the gene TAP2 was identified. Expression of TAP2 and its molecular chaperone, TAP1, were validated by quantitative PCR, and invitro functional experiments were performed. The results showed that patients with DHS have higher mRNA levels of TAP1 and TAP2 and an enhanced capacity for antigen-presenting cells activating dapsone-specific T cells compared with dapsone-tolerant controls. Activation of dapsone-specific T cells was inhibited when TAP function of antigen-presenting cells was impaired. This study shows that epigenetic regulation of TAP1 and TAP2 affects the function of antigen-presenting cells and is a critical factor that mediates the development of DHS.

A case report of Dapsone Hypersensitivity Syndrome in a Child with Lepromatous Leprosy and Potential Genetic Element

Sri Lanka Journal of Medicine is the official journal of the Kandy Society of Medicine. It is a peer-reviewed journal currently published biannually. Original articles, reviews, brief reports, case reports, points of view, and letters to the editor, in all fields of medical science and practice are accepted for publication.The Sri Lanka Journal of Medicine is now indexed in DOAJ

DAPSONE HYPERSENSITIVITY SYNDROME - A CASE REPORT AT TERTIARY CARE HOSPITAL

Dapsone a sulfonamide drug used mainly in the treatment of Leprosy and various other several bacterial infections. Rarely Dapsone can lead to hypersensitive reaction characterised by fever, yellowish sclera and other systems involved. We report a 17 year old patient presented with fever, jaundice and generalised edema with a history of borderline tuberculoid leprosy receiving Dapsone, clofizamine and Rifampicin. After confirming Dapsone Hypersensitivity Syndrome, Dapsone is stopped and treated with corticosteroids, antibiotics, Glutathione and patient recovered gradually.

Implementation of genetic screening test to reduce the incidence of dapsone hypersensitivity syndrome among patients with leprosy in Papua, Indonesia: a study protocol.

IntroductionThe mainstay of leprosy treatment is multidrug treatment (MDT), which contains rifampicin, dapsone and clofazimine. The occurrence of dapsone hypersensitivity syndrome (DHS), a sudden, potentially fatal and traumatic adverse reaction due to dapsone, may affect treatment adherence and may result in fatality if untreated. Before MDT administration, screening for HLA-B*13:01 in patients with leprosy can potentially reduce DHS risk. The study aims to assess the effectiveness of using a screening test for HLA-B*13:01 in reducing the incidence of DHS and to evaluate the feasibility of using the quantitative PCR-based screening tool as DHS predictors before dapsone administration using individual patient testing in a referral centralised-lab model.Methods and analysisA total of 310 newly diagnosed patients with leprosy will be recruited from health centres in two highly endemic districts in Indonesia. Dried blood will be taken on filter paper as the specimen receptacle to collect DNA from the patients and transported at room temperature to the leprosy referral laboratory before MDT administration. Checking for HLA-B*13:01 from human DNA is performed using the Nala PGx 1301 V.1 kit. The results will be shared with the leprosy health workers on the site via phone call and courier. Patients with a positive test result will be treated with MDT without dapsone, and patients with a negative result will be treated with complete MDT. Physical examination (weight, height, skin, muscle and nerve function examination), complete blood tests (including renal function test) will be carried out at baseline. Follow-up will be performed at the fourth and eighth weeks to observe any development of adverse drug reactions.Ethics and disseminationThe ethical approval for the study was issued by the Ethical Committee of the National Institute of Health Research and Development, Ministry of Health, Indonesia. Written informed consent will be sought from all participants.

Dapsone Induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome - A Case Report

A 50-year-old male Sudanese patient presented with a three-week history of jaundice, high-grade fever, and mucocutaneous eruption. For last months he was on compound therapy for leprosy, which had been confirmed recently. The patient’s face was prominent, along with the erythematous dusky morbilliform rash covering all the body. On examination, we detected hepatosplenomegaly and generalized lymphadenopathy. Laboratory investigations revealed hepatorenal impairment, and hematological analysis revealed leukocytosis mainly due to eosinophilia. The clinical and laboratory findings interpretation ranked DRESS or Drug-Induced Hypersensitivity Syndrome (DIHS) on top of possible causes before Dapsone Hypersensitivity Syndrome (DHS) and lepra reactions. We promptly discontinued MDT, admitted him to the dermatological ward. Two skin biopsies were sent to two different histopathologists, MF was suggested by one and Sezary syndrome by the other one. Besides the general conservative measures and vital functions monitoring, he received systemic and topical steroids. However, unfortunately, within the next three weeks, his condition deteriorated, and passed away from multi-systems failure.

HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients.

HLA-B*13:01 allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR). We investigated the association of HLA alleles and cytochrome P450 (CYP) alleles with dapsone-induced SCAR in Thai non-leprosy patients. A prospective cohort study, 16 Thai patients of dapsone-induced SCARs (5 SJS-TEN and 11 DRESS) and 9 Taiwanese patients of dapsone-induced SCARs (2 SJS-TEN and 7 DRESS), 40 dapsone-tolerant controls, and 470 general Thai population were enrolled. HLA class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). CYP2C9, CYP2C19, and CYP3A4 genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with HLA-B*13:01 and HLA-B*13:02 alleles by the molecular docking approach. Among all the HLA alleles, only HLA-B*13:01 allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67–198.21, p = 5.3447 × 10−7), SJS-TEN (OR = 36.00, 95% CI = 3.19–405.89, p = 2.1657 × 10−3), and DRESS (OR = 40.50, 95% CI = 6.38–257.03, p = 1.0784 × 10−5) as compared to dapsone-tolerant controls. Also, HLA-B*13:01 allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67–149.52, p = 2.8068 × 10−7) and Taiwanese (OR = 31.50, 95% CI = 4.80–206.56, p = 2.5519 × 10−3). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the HLA-B*13:01 allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the HLA-B*13:01 allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.

DAPSONE HYPERSENSITIVITY SYNDROME: A COMPLICATION OF DAPSONE THERAPY

Dapsone is chemically sulfonamide with its leprostatic mechanism used in the treatment of Hansen’s disease. It is one of the safest drugs in leprosy patients. Apart from its safety, it is associated with various adverse effects such as hemolytic anemia, allergic dermatitis, agranulocytosis, methaemoglobinemia, and dapsone hypersensitivity syndrome (DHS). DHS typically presents with fever, skin eruptions, Jaundice, and hepatomegaly (organ involvement). We present a case of 35-year-old female attended to Government General Hospital with complaints of fever, skin rashes, and yellowish discoloration of the eyes. She had past medication history of dapsone taken for paucibacillary leprosy for 4 weeks. Her symptoms appeared after a month and become intolerable to dapsone. Laboratory investigations revealed hepatomegaly, anemic with jaundice. Based on dermatological examination, her diagnosis was confirmed as DHS. The drug was stopped and the patient was treated with drugs for the symptomatic cure. She was recovered from her condition and the multibacillary leprosy multidrug treatment regimen was continued without dapsone.

Conundrum of recurrent erythema nodosum leprosum and dapsone hypersensitivity syndrome complicating pediatric leprosy

Introduction: Leprosy, a chronic infectious disease affecting the skin and peripheral nerves, has been considered a disease of adults due to its long incubation period, but in endemic regions like the Indian subcontinent, pediatric leprosy cases continue to rise reflecting active disease transmission in the community. Case report: We describe a case of bordeline lepromatous leprosy in a child complicated by severe type 2 lepra reaction and dapsone hypersensitivity syndrome. Conclusion: Pediatric leprosy cases though commonly paucibacillary, can also present with a high bacillary burden. Complicated leprosy cases need nuanced care and highlight the importance of adequate clinical exposure to leprosy cases, so that such cases can be confidently managed.

Dermatological patients in the Intensive Care Unit – a hospital record based retrospective study

Background: Various dermatological conditions can be life threatening and may require admission in the intensive care unit for monitoring and management. We carried out this study to assess the profile of dermatological admissions in the intensive care unit. Materials and Methods: It was a cross sectional retrospective study in which the records of all patients of various dermatological disorders admitted in the intensive care unit over a period of three years was studied and the clinical details were assessed. Results: Over a period of three years, a total of 16 patients (M:F 10:6), aged between 16-71 years (mean 46±2.31 years) were admitted with an underlying dermatological disorder. The most common condition requiring admission was Stevens Johnsons Syndrome (n=5), followed by Pemphigus vulgaris (n=4), erythroderma(n=2), pustular psoriasis, dermatomyositis, necrotizing faciitis, dapsone hypersensitivity syndrome and cutaneous lymphoma in 1 each. Interventions like mechanical ventilation were required in 2 patients, inotropic support in 2 patients, central venous line placement, renal replacement therapy and tracheostomy in one patient each. The mean duration of ICU stay was 14.2 days and mortality was the outcome in 2 patients of pemphigus vulgaris which was attributed to septicemia and shock. Conclusions: Dermatological disorders can cause significant morbidity and may require proper care in the intensive care unit. Timely initiation of intensive care can help in reducing the morbidity and preventing mortality.

Validation study of HLA-B*13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia.

Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13:01, a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10-9, confirming the strong association of HLA-B*13:01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.

S2695 A Rare Drug Reaction: A Case of Dapsone Hypersensitivity Syndrome

INTRODUCTION: Dapsone is used to treat a variety of infectious and inflammatory disorders, and can be associated with a number of adverse side effects and events including a rare clinical entity known as dapsone hypersensitivity syndrome (DHS). This is a case of a 22-year-old female presenting with fever, hemolytic anemia, and acute hepatitis, found to have DHS. CASE DESCRIPTION/METHODS: A 22-year-old female with macular lymphocytic arteritis presented to the ED with one week of abdominal pain and fevers. She had been initiated on dapsone one month prior for her arteritis, but had stopped taking dapsone when her symptoms began. Prior to therapy, her G6PD level was normal. On presentation, she was febrile and tachycardic, with exam notable for diffuse abdominal tenderness. Her mental status was intact. Her admission labs were notable for hemolytic anemia and transaminitis with a hepatocellular injury pattern. Her INR was normal and Coomb’s test was negative. A right upper quadrant ultrasound showed gallbladder wall thickening and mild intrahepatic biliary ductal dilation. She remained febrile despite a negative infectious workup and empiric antibiotic therapy. A broad workup for causes of acute and chronic liver injury revealed no obvious etiology. Five days into her admission, her eosinophil count increased from 0.6 to 15, and she developed a new rash on her upper extremities. Given the concern for DRESS syndrome, specifically a variant known as DHS, she was started on prednisone and underwent liver and skin biopsies, which were consistent with DHS. Her labs and symptoms improved after a prolonged taper of prednisone. A RUCAM (Roussel Uclaf Causality Assessment Method in DILI) final score was calculated in this case to be eight, suggesting probable causality. DISCUSSION: DHS is a severe idiosyncratic reaction and variant of DRESS that occurs in 0.5 to 3.6% of patients treated with dapsone, and is associated with a fatality rate of 10%. Symptoms of DHS include fever, rash and lymphadenopathy, and typically arise within weeks of initiating dapsone, but can present as late as six months after its use. The mechanism by which DHS occurs remains unclear, although there is evidence that variability in the production of reactive metabolites plays a role in sulfonamide hypersensitivity reactions. Due to the rarity of DHS and the potentially fatal associated organ dysfunction, it is important to make an early diagnosis in order to promptly withdraw dapsone and administer glucocorticoids.Figure 1.: Magnification 10x. Severe acute hepatitis with mixed triaditis, interface and lobular hepatitis, and cholestasis, consistent with drug-induced liver injury.Figure 2.: Magnification 30x. Hepatic parenchyma shows zone 3 inflammation associated with prominent cholestasis and scattered single cell necrosis.

Dapsone induced hypersensitivity syndrome: a case report

Dapsone is an anti-leprotic drug. It may cause a severe adverse effect known as dapsone hypersensitivity syndrome which involves fever, chills, rash, and internal organ involvement. We report a case of a patient who is 30 years old male presented with fever, skin desquamation, and hepatitis. The case is being reported to emphasize the need to diagnose and manage dapsone hypersensitivity syndrome.

The adverse drug effects of dapsone therapy in leprosy: a systematic review

Objectives: To establish the rate of adverse drug reactions (ADR) when dapsone is given in leprosy multi-drug therapy (MDT). This paper reviews the reporting of ADRs by systematic review of the databases Ovid Medline, Ovid Embase and Global Health according to pre-specified eligibility criteria. Results: The search identified 5859 relevant citations. These publications were divided into two data sets and reviewed for their documentation of ADRs. One hundred and fourteen publications reported ADR as the primary outcome and 98 papers reported the efficacy of treatment. Of the 114 papers included, 79 were case reports, 23 retrospective studies, 7 prospective studies and 7 literature reviews. Dapsone Hypersensitivity Syndrome (DHS) was reported most frequently as an adverse effect, then anaemia (haemolytic and not otherwise specified), cutaneous eruptions, gastrointestinal disturbance and hepatitis. Eleven studies report a mean rate of DHS as 1.22% and an average fatality rate in 8 studies of 11.24%. Of the 98 papers reporting treatment efficacy, 33 papers reported ADRs to medications other than dapsone and 36 publications had no documentation of adverse effects. Conclusion: Most publications report ADRs in case reports, many from India. DHS was the most commonly reported ADR, followed by individual features of the syndrome. Many studies lack patient information with many not reporting ADRs. Our findings show that improved prospective monitoring of adverse events associated with dapsone is needed. We propose that all patients should be tested with a full blood count before starting MDT and repeated after 4–8 weeks with mandatory follow-up. This would facilitate detecting ADRs including DHS and dapsone-associated anaemias.

The HLA-B*13:01 and the dapsone hypersensitivity syndrome in Korean and Asian populations: genotype- and meta-analyses

ABSTRACT Background The human leukocyte antigen (HLA)-B*13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations. Research design and methods From the Korean nationwide registry, seven subjects with previous DHS were included. Their HLA allele/phenotype frequencies were compared with 8 dapsone-tolerant subjects recruited from a single institution, and general population (n = 485) in Korea. The authors also performed a meta-analysis with these data using previous Chinese and Thai studies. Results Among the seven DHS subjects, 85.7% presented with the HLA-B*13:01 allele. The HLA-C*03:04, HLA-DRB1*12:02 (both in linkage disequilibrium with HLA-B*13:01), and HLA-A*02:01 alleles were also presented in 85.7%, 71.4%, and 71.4%, respectively. Subjects with HLA-B*13:01 were susceptible to developing DHS compared to dapsone-tolerant controls (odds ratio [OR]: 73.667) and the Korean general population (OR: 139.500). HLA-C*03:04 (OR: 40.935), HLA-DRB*12:02 (OR: 36.613), and HLA-A*02:01 (OR: 5.862) showed similar results. In meta-analysis, HLA-B*13:01 was associated with dapsone-induced hypersensitivity (overall OR: 42.692), and subgroup analyses according to the control types demonstrated similar results (OR:43.694 and 41.866, respectively). Conclusions Similar to previous Asian population studies, HLA-B*13:01 is significantly associated with the risk of DHS in Korea. These associations may be useful for preventing DHS and improving drug safety.

594 Dynamic cytokine profiles combined with ELISPOT assay are useful in immunologically confirming the dapsone hypersensitivity syndrome

Background: Dapsone hypersensitivity syndrome (DHS) is induced by drug-specific T cells. The specific dynamic cytokine profiles of DHS are unknown and the diagnosis of DHS in clinical practice remains a challenge. Objective: To investigate the DHS specific dynamic cytokine profiles, and explore specific enzyme-linked immunospot (ELISPOT) assay in the diagnosis of DHS. Methods: 14 types of cytokine levels (IFN-γ, Fas Ligand, Granzyme B, IL-4, IL-5, IL-6, IL-10, IL-13, IL-15, IL-17A, IL-21, IL-22, IL-23, and TNF-α) in DHS patients and dapsone tolerant patients carrying HLA-B*13:01 were analyzed using Luminex Bioplex assay. The performance of an IFN-γ/Granzyme B/IL-5 three-color fluoroSpot ELISPOT assay and Single-color ELISPOT assays based on traditional enzyme-tagged reagents in immunologically confirming DHS was evaluated in 16 DHS patients, four dapsone tolerant patients and 12 healthy donors. Results: Dynamic cytokine profiles showed that IFN-γ, IL-5, IL-13, Granzyme B and TNF-α were specifically up-regulated expression in DHS. In 16 patients with DHS, 9 (56.25%) patients were positive on IFN-γ ELISpot, 11 (68.75%) patients were positive on Granzyme B ELISpot and 11 (68.75%) patients were positive on IL-5 ELISpot, and when combination of IFN-γ, Granzyme B and IL-5 ELISPOT, the sensitivity increased to 87.5% (14/16) with the specificity of 100%. onclusions: An IFN-γ/Granzyme B/IL-5 ELISPOT assay with sensitivity of 87.5% was established, which could be treated as a promising tool in the diagnosis of DHS.