Indian Journal of Rheumatology

REVIEW ARTICLE
Year
: 2019  |  Volume : 14  |  Issue : 5  |  Page : 59--66

Drug reaction with eosinophilia and systemic symptoms syndrome


KC Shanoj, Sneha Joseph, Padmanabha Shenoy 
 Centre for Arthritis and Rheumatism Excellence, Kochi, Kerala, India

Correspondence Address:
Dr. Padmanabha Shenoy
Centre for Arthritis and Rheumatism Excellence, Nettoor, Kochi - 682 040, Kerala
India

Abstract

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a delayed form of severe cutaneous adverse reaction (SCAR) seen in association with certain drugs, especially anticonvulsants and allopurinol. Unlike other SCARs, DRESS is associated with significant systemic involvement such as fever, lymphadenopathy, eosinophilia, renal failure, transaminitis, and myocarditis. Because of delayed onset of symptoms and a persistent course even after discontinuation of culprit drug, DRESS can mimic a variety of rheumatological disorders. Even though glucocorticoids are the mainstay of treatment, unlike other SCARs, DRESS is associated with a high incidence of viral reactivation, especially with members of the human Herpesviridae family. Early identification of the viral activation and prompt therapy is critical in the management of DRESS.



How to cite this article:
Shanoj K C, Joseph S, Shenoy P. Drug reaction with eosinophilia and systemic symptoms syndrome.Indian J Rheumatol 2019;14:59-66


How to cite this URL:
Shanoj K C, Joseph S, Shenoy P. Drug reaction with eosinophilia and systemic symptoms syndrome. Indian J Rheumatol [serial online] 2019 [cited 2020 Jan 22 ];14:59-66
Available from: http://www.indianjrheumatol.com/text.asp?2019/14/5/59/272151


Full Text



 Introduction



Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse reaction (SCAR) associated with skin rash, fever, eosinophilia, lymphadenopathy, and multiple internal organ involvement. DRESS typically presents 3 weeks to 3 months after the initiation of culprit drug, with many of the systemic manifestations appearing weeks to months after the onset of symptoms, making the diagnosis and management even more challenging. Because of these varied presentations, DRESS can mimic infection, sepsis, systemic lupus erythematosus, and adult-onset Still's disease.

Most of the initial description of DRESS was named as per the culprit drugs, such as hydantoin syndrome and dapsone syndrome. The term DRESS syndrome was first introduced by Bocquet et al. in 1996 to unify various severe drug reactions such as allopurinol hypersensitivity syndrome, sulfone syndrome, drug-induced pseudolymphoma, and anticonvulsant hypersensitivity syndrome.[1] Japanese investigators coined the term drug-induced hypersensitivity syndrome (DIHS) to describe the same syndrome. The term DRESS will be used in this review from here on to describe this syndrome.

Most of the adverse drug reactions (ADRs) are dose-dependent and predictable. However, 20% of the ADRs are a dose-independent allergic reaction to the drug. Majority of allergic ADRs are milder and nonlife-threatening such as fixed drug eruption, maculopapular exanthema, and urticaria. On the other hand, SCAR is associated with extensive skin involvement and potentially life-threatening. Disorders included under SCAR are DRESS syndrome, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).[2] The European Registry of SCAR (RegiSCAR) established for continuous surveillance of SCAR including DRESS, SJS, TEN, and AGEP established a diagnostic scoring for DRESS in 2007. Characteristic features of DRESS include significant systemic involvement, minimal epidermal lysis,[3] and association with viral reactivation, especially with the viruses of the herpes family.[4],[5],[6] In fact, many of the late complications of DRESS are due to the viral reactivation.[7]

 Search Strategy



A systematic search of the literature was conducted on the electronic database in the pubmed, using search criteria 'DRESS' and 'Drug Reaction AND Eosinophilia'. Only papers in the English language was selected for the review Search criteria yielded a total of around 5000 articles. With the consensus of the authors, about 50 articles were selected and the references in each article were also reviewed where necessary.

 Etiology



Aromatic antiepileptic drugs such as phenytoin, carbamazepine, and lamotrigine are the most common culprit agents to cause DRESS, accounting for 35% of cases.[8] Allopurinol was the second most common cause of DRESS as per the RegiSCAR study.[8] Febuxostat can also cause DRESS in patients with chronic kidney disease.[9] Among the antimicrobials, sulfonamides, especially sulfasalazine and dapsone, were the most commonly reported drugs,[10] followed by penicillins, antitubercular drugs, and cephalosporins.[11] Other classes of drugs that are reported to cause DRESS include nonsteroidal anti-inflammatory drugs (NSAIDs), sorafenib, hydroxychloroquine, amitriptyline, omeprazole, and nevirapine to name a few [Table 1].[12],[13],[14]{Table 1}

 Clinical Features



DRESS typically starts as a flu-like illness with fever, rash, sore throat, and lymphadenopathy. In most of the cases, symptoms appear 3 weeks to 3 months following the initiation of an offending drug.[16] However, on re-exposure, symptoms can appear earlier with more severe manifestation.[17] Clinical features and onset of symptoms vary with the culprit drug [Table 2].[11] Fever is seen in 64%-90% of cases,[8],[12],[18] which is almost always present in dapsone-induced DRESS (100%) but seen in only 50% of cases in patients with allopurinol-induced DRESS.[11] Fever is usually high grade and tends to last weeks after continuation of the culprit drug. In most of the cases, fever is accompanied by the presence of pruritic skin rash. The rash usually begins as erythematous macules, pustules, or eczema-like lesions which is mildly pruritic and symmetric in distribution. Associated facial edema with pinhead-sized pustules is seen in 79% of the cases and considered as a hallmark of DRESS.[8],[13] Typically, skin rash involves more than half of the body surface, which later tends to become confluent with associated blister formation. However, epidermal necrosis and bullae are not seen in DRESS. Mucosal surfaces, palms, and soles are usually spared in DRESS; however, their involvement does not rule out the diagnosis.[3] As in case of fever, skin rash tends to persist for weeks to months even after discontinuation of culprit drug.[19]{Table 2}

 Internal Organ Involvement



Internal organ involvement in DRESS is associated with significant morbidity and mortality, most commonly affecting the hematopoietic, hepatic, and renal system. Frequently, the appearance of organ involvement can be delayed even weeks to months after the onset of skin rash and can be missed as a complication of DRESS being mistakenly labeled as infection or autoimmune diseases.[8],[20]

 Hematological Manifestations



Eosinophilia is the most common hematological manifestation of DRESS reported in 57%-95% of cases.[12],[14],[18],[21] Most often, eosinophilia is mild to moderate but can be severe enough to mimic hypereosinophilic syndrome.[22] Atypical lymphocytosis is seen in up to 67% of cases.[13] Neutrophilia is reported in 78% of cases, especially in the early phase of DRESS; on the other hand, monocytosis is more common in the later phase, seen in 69% of cases.[8] Cytopenias such as anemia, lymphopenia, and thrombocytopenia may be seen but are less frequent manifestations of DRESS.

Lymphadenopathy is seen in 54%-71% of DRESS,[8],[14],[18] more common with NSAIDs (60%) and least common in allopurinol-induced DRESS.[11] Because of prolonged fever and splenomegaly, DRESS can mimic lymphoma. Histopathology also simulates lymphoma, justifying the earlier term pseudolymphoma.[23]

 Visceral Manifestations



The most common visceral involvement is transient transaminitis, which is usually self-limiting. Hepatic involvement is seen in 75%-94% of cases and can be a delayed presentation. Paradoxical worsening of the symptoms can occur after the withdrawal of the culprit drug. Late-onset hepatitis may be associated with viral reactivation, especially with cytomegalovirus (CMV). Apart from hepatitis, cholestasis is also described in association with DRESS. Even though rare, fulminant hepatic failure can complicate DRESS which is the most common cause of mortality.[6],[8],[14],[18]

Renal involvement is more frequent with allopurinol (60%) compared with other drugs.[24],[25] Most of the cases are transient with a mild increase in blood urea nitrogen and serum creatinine. Urine analysis may show the presence of eosinophils. Biopsy studies have demonstrated interstitial nephritis with intense lymphocyte infiltrates and tubular necrosis with an absence of deposits in immunofluorescence.[26] Most of the cases resolve without any sequela. However, there are case reports of progressive renal failure in patients with DRESS syndrome. Risk factors for renal involvement in DRESS are preexisting renal disease and old age.

Cardiac involvement was considered to be rare in DRESS. However, a recent retrospective analysis by Intarasupht et al. reported a prevalence of 19.1%.[27] Heart involvement in DRESS can be due to hypersensitivity myocarditis or acute necrotizing eosinophilic myocarditis.[28] Clinical features are often delayed with dyspnea, chest pain, tachycardia, hypotension, and features of congestive cardiac failure. Hypersensitivity myocarditis is usually self-limiting. On the other hand, necrotizing myocarditis has a mortality rate of 50%, with a median survival rate of 3-4 days.[20],[28] Minocycline- and ampicillin-associated DRESS has a higher incidence of cardiac manifestations compared to other agents. Cardiac manifestations can also cause long-term sequelae such as thromboembolism, valvular regurgitation, and restrictive cardiomyopathy.[20]

Lung involvement is usually mild in DRESS, presenting with impaired pulmonary function, pleuritis, or pneumonitis. Nevertheless, severe pulmonary involvement with acute respiratory distress syndrome can occur in a minority of patients, especially with the DRESS syndrome associated with minocycline or abacavir use.[21]

Other rare manifestations reported in DRESS are neurological involvement such as meningitis or meningoencephalitis, arthritis, myositis, and pancreatitis.[2],[8]

 Pathogenesis



Role of immune cells

Cutaneous ADR (cADR) is a T-cell mediated hypersensitivity reaction against a drug or its metabolite. However, unlike other cADRs, the acute phase (day 1-11) of DRESS is associated with an exponential increase in peripheral T regulatory (Treg) cells, mainly induced Treg cells (iTreg).[3] On the other hand, during resolution, Treg number drops with an associated increase in the Th17 lymphocytes. Even though the data regarding the above hypothesis are limited owing to the rarity of the condition, there seems to be a direct link between the imbalance of Treg cells and DRESS.

Ushigome et al. reported the depletion of proinflammatory monocytes in the early phase of DRESS, causing Treg expansion.[29] What drives this unusual T-cell response is not well elucidated. An increase in the iTreg cells coincides with an increased risk of herpesvirus reactivation and various internal organ involvement. Similarly, many of the autoimmune manifestations are seen in the resolution phase of DRESS. The difference between acute and resolution phase is depicted in [Table 3].{Table 3}

Recently, Yazicioglu et al. compared peripheral B-lymphocytes in DRESS syndrome, maculopapular drug rash, and viral exanthem. Peripheral B-cells were significantly lower in DRESS in comparison with other two conditions.[30] These findings add on to the complex picture of immune dysregulation in patients with DRESS.

In summary, the early phase of DRESS is associated with significant immunosuppression with associated viral reactivation and the late phase is associated with immune reconstitution and autoimmune phenomenon [Figure 1].{Figure 1}

Role of genetics

As expected in a T-cell-mediated hypersensitivity syndrome, human leukocyte antigen (HLA) is the most important susceptibility factor that predisposes to DRESS. Various associations between HLA and specific drugs are depicted in [Table 4]. Apart from HLA, drug metabolisms such as slow acetylators and cytochromeP polymorphisms also influence the susceptibility for DRESS.[13]{Table 4}

Role of viral infection

Viral infections can influence the onset and course of DRESS syndrome. Preceding viral infections, especially herpes zoster, are common in patients with DRESS.[3],[6] Viral infection may be acting as a trigger in the initiation of immune dysregulation.

Unlike other autoimmune and hypersensitivity disorders, DRESS is associated with significant viral reactivation influencing the visceral organ involvement and overall prognosis. Up to 60%-80% of patients with DRESS show evidence of viral reactivation with members of the herpes family.[13] Human herpesvirus-6 (HHV-6) is the first viral DNA that is detectable in DRESS, appearing 3-5 weeks after the onset of the symptoms.[16] Recent studies have demonstrated sequential reactivation of other viruses in the herpes family. Followed by HHV-6 appearance, Epstein-Barr virus (EBV), HHV-7, and CMV DNA may become detectable in the serum.[38] CMV reactivation usually occurs 3-7 weeks after the onset of DRESS. CMV reactivation is especially significant as it is associated with significant visceral involvement such as hepatitis, pneumonitis, gastroenteritis, and myocarditis.[7],[39],[40] Prompt identification of viral reactivation and treatment with antiviral treatment is crucial in improving the overall outcome of DRESS.

 Diagnosis



The diagnosis of DRESS is challenging as many clinical and laboratory features are transient and appear during a later phase of the disease. There are two validated diagnostic criteria for the diagnosis of DRESS. The RegiSCAR group proposed a diagnostic score depending on the clinical and laboratory features. Total score qualifies the case as definite, probable, possManagement of DrugManagement of Drug Reaction with Eosinophilia and Systemic Symptomsible, or not a case.[8] The Japanese counterpart Japan Severe Adverse Reaction (JSCAR) research group proposed a validation score based on the clinical and laboratory features for DIHS.[16] A diagnosis of typical (definite) DIHS requires fulfillment of all seven criteria, including evidence of HHV-6 reactivation. On the other hand, the diagnosis of atypical (probable) DIHS is made in the presence of typical clinical features in the absence of evidence for HHV-6 reactivation. The diagnostic criteria in DRESS are depicted in [Table 5] and [Table 6].{Table 5}{Table 6}

 Management of Drug Reaction With Eosinophilia and Systemic Symptoms



Because of the variability of clinical features and complications, the management of DRESS requires a high index of suspicion and a multidisciplinary approach. Withdrawal of the drug at the earliest suspicion of DRESS should be made. However, hypersensitivity to the drug can show class phenomenon so that unnecessary antibiotics in suspicion of infection should be avoided. Moreover, DRESS can be associated with paradoxical worsening after discontinuation of the drug, which can cause significant diagnostic and treatment dilemma.

Corticosteroids (CSs) are the mainstay in the management of DRESS, especially in the acute phase. Prednisolone is required at a dose of 1 mg/kg required for most of the patients with moderate and severe manifestations.[3] In case of life-threatening conditions, pulse methylprednisolone or Intravenous immnunoglobulin (IVIG) may be required. As the disease tends to flare on tapering CS, slow tapering of CS is advocated, typically, over 2-3 months.[13] However, slower taper over 3-12 months may be required for patients with severe manifestations. There are no randomized controlled trials in the treatment of DRESS supporting the utility of CS in the management of DRESS owing to the low prevalence of this disorder. There are reports of effective treatment of DRESS without systemic CS.[41],[42] Uhara et al. reported an effective treatment of 12 patients without the use of systemic CS.[41] However, most such cases are milder without much visceral involvement, and avoidance of systemic steroid in DRESS syndrome can be associated with significant short- and long-term complications. Ushigome et al. reported a significant increase in the EBV reactivation in patients not receiving systemic CS in the early phase of the disease. EBV reactivation in DRESS was associated with a higher incidence of the autoimmune phenomenon.[43] The current evidence favors the use of systemic GC in severe cases and topical CS in mild disease. In the absence of visceral involvement, the French Dermatology Society recommends the use of topical CS and antihistamine drugs.[44] Viral DNA should be assessed during the course of the disease, and in the presence of viral reactivation with systemic signs, the French Dermatology Society recommends glucocorticoids plus antivirals (ganciclovir).[44]

The evidence for the use of immunosuppressive drugs in DRESS is much less, especially in patients with insufficient response to GC. Cyclosporine was found to be useful in multiple case reports in severe DRESS.[45],[46],[47],[48],[49] However, there are two case reports of fatal outcome with the use of cyclosporine in DRESS, both with cardiac involvement.[50],[51] Other immunosuppressive agents that have shown benefit in steroid-resistant cases are mycophenolate mofetil, cyclophosphamide, and rituximab.[13],[52]

 Prognosis



The prognosis of DRESS depends on the culprit drug, presence of viral reactivation, and systemic organ involvement. Allopurinol- and minocycline-induced DRESS are more severe with a prolonged course. Various complications of DRESS are depicted in [Table 7]. The mortality rate of DRESS was estimated to be 10%;[2] however, recent RegiSCAR data showed a much lower mortality rate.[8],[53]{Table 7}

 Conclusion



DRESS syndrome is a multisystem drug adverse reaction with fever and eosinophilia. Clinical presentation is often protracted with multiple flares which can confuse with various infections, rheumatological disorders, and malignancies. Viral reactivation and autoimmune phenomena complicate the course of the disease. Prompt recognition of complication is vital in the management of DRESS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug rash with eosinophilia and systemic symptoms: DRESS). Semin Cutan Med Surg 1996;15:250-7.
2Shiohara T, Kano Y, Mizukawa Y, Aoyama Y. Viral reactivation in cutaneous adverse drug reactions. In: Shear NH, Dodiuk-Gad RP, editors. Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions: Current and Future Trends. Singapore: Springer Singapore; 2019. p. 55-65. [Last accessed on 2019 Aug 27].
3Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): An update in 2019. Allergol Int 2019;68:301-8.
4Suzuki Y, Inagi R, Aono T, Yamanishi K, Shiohara T. Human herpesvirus 6 infection as a risk factor for the development of severe drug-induced hypersensitivity syndrome. Arch Dermatol 1998;134:1108-12.
5Tohyama M, Yahata Y, Yasukawa M, Inagi R, Urano Y, Yamanishi K,et al. Severe hypersensitivity syndrome due to sulfasalazine associated with reactivation of human herpesvirus 6. Arch Dermatol 1998;134:1113-7.
6Shiohara T, Ushigome Y, Kano Y, Takahashi R. Crucial role of viral reactivation in the development of severe drug eruptions: A comprehensive review. Clin Rev Allergy Immunol 2015;49:192-202.
7Asano Y, Kagawa H, Kano Y, Shiohara T. Cytomegalovirus disease during severe drug eruptions: Report of 2 cases and retrospective study of 18 patients with drug-induced hypersensitivity syndrome. Arch Dermatol 2009;145:1030-6.
8Kardaun SH, Sekula P, Valeyrie-Allanore L, Liss Y, Chu CY, Creamer D, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): An original multisystem adverse drug reaction. Results from the prospective regiSCAR study. Br J Dermatol 2013;169:1071-80.
9Paschou E, Gavriilaki E, Papaioannou G, Tsompanakou A, Kalaitzoglou A, Sabanis N, et al. Febuxostat hypersensitivity: Another cause of DRESS syndrome in chronic kidney disease? Eur Ann Allergy Clin Immunol 2016;48:251-5.
10Di Palma-Grisi JC, Vijayagopal K, Muslimani MA. Case reports of DRESS syndrome and symptoms consistent with DRESS syndrome following treatment with recently marketed monoclonal antibodies. Autoimmune Dis 2019;2019:7595706.
11Sim DW, Yu JE, Jeong J, Jung JW, Kang HR, Kang DY, et al. Variation of clinical manifestations according to culprit drugs in DRESS syndrome. Pharmacoepidemiol Drug Saf 2019;28:840-8.
12Skowron F, Bensaid B, Balme B, Depaepe L, Kanitakis J, Nosbaum A,et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): Clinicopathological study of 45 cases. J Eur Acad Dermatol Venereol 2015;29:2199-205.
13Martínez-Cabriales SA, Rodríguez-Bolaños F, Shear NH. Drug reaction with eosinophilia and systemic symptoms (DReSS): How far have we come? Am J Clin Dermatol 2019;20:217-36.
14Wang L, Mei XL. Drug reaction with eosinophilia and systemic symptoms: Retrospective analysis of 104 cases over one decade. Chin Med J (Engl) 2017;130:943-9.
15Greite R, Deutsch K, Bräsen JH, von Vietinghoff S. Azathioprine hypersensitivity syndrome in anti-myeloperoxidase anti-neutrophil cytoplasmic antibody-associated vasculitis. Clin Kidney J 2019;12:89-91.
16Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): A reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int 2006;55:1-8.
17De A, Rajagopalan M, Sarda A, Das S, Biswas P. Drug reaction with eosinophilia and systemic symptoms: An update and review of recent literature. Indian J Dermatol 2018;63:30-40.
18Hiransuthikul A, Rattananupong T, Klaewsongkram J, Rerknimitr P, Pongprutthipan M, Ruxrungtham K. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS): 11 years retrospective study in Thailand. Allergol Int 2016;65:432-8.
19Corneli HM. DRESS syndrome: Drug reaction with eosinophilia and systemic symptoms. Pediatr Emerg Care 2017;33:499-502.
20Thongsri T, Chularojanamontri L, Pichler WJ. Cardiac involvement in DRESS syndrome. Asian Pac J Allergy Immunol 2017;35:3-10.
21Cho YT, Yang CW, Chu CY. Drug reaction with eosinophilia and systemic symptoms (DRESS): An interplay among drugs, viruses, and immune system. Int J Mol Sci 2017;18. pii: E1243.
22Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, Finzi L, et al. The DRESS syndrome: A literature review. Am J Med 2011;124:588-97.
23Saltzstein SL, Ackerman LV. Lymphadenopathy induced by anticonvulsant drugs and mimicking clinically pathologically malignant lymphomas. Cancer 1959;12:164-82.
24Aatif T, Fatihi J, El Annaz H, Qamouss O. Allopurinol-induced drug reactions with eosinophilia and systemic symptoms syndrome with interstitial nephritis. Indian J Nephrol 2018;28:477-81.
25Qadri I, Zeng X, Guo R, Koratala A. Acute interstitial nephritis and DRESS syndrome without eosinophilia associated with cefepime. BMJ Case Rep 2017;2017. pii: bcr-2017-221401.
26Kano Y, Ishida T, Hirahara K, Shiohara T. Visceral involvements and long-term sequelae in drug-induced hypersensitivity syndrome. Med Clin North Am 2010;94:743-59, xi.
27Intarasupht J, Kanchanomai A, Leelasattakul W, Chantrarat T, Nakakes A, Tiyanon W. Prevalence, risk factors, and mortality outcome in the drug reaction with eosinophilia and systemic symptoms patients with cardiac involvement. Int J Dermatol 2018;57:1187-91.
28Bourgeois GP, Cafardi JA, Groysman V, Hughey LC. A review of DRESS-associated myocarditis. J Am Acad Dermatol 2012;66:e229-36.
29Ushigome Y, Mizukawa Y, Kimishima M, Yamazaki Y, Takahashi R, Kano Y, et al. Monocytes are involved in the balance between regulatory T cells and th17 cells in severe drug eruptions. Clin Exp Allergy 2018;48:1453-63.
30Yazicioglu M, Gokmirza Ozdemir P, Turgut B, Sut N. Serum soluble fas ligand levels and peripheral blood lymphocyte subsets in patients with drug-induced maculopapular rashes, dress, and viral exanthemas. Allergol Immunopathol (Madr) 2019. pii: S0301-0546(19)30042-4.
31Kim SH, Lee KW, Song WJ, Kim SH, Jee YK, Lee SM, et al. Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res 2011;97:190-7.
32McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperavičiūtė D, Carrington M, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 2011;364:1134-43.
33Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR, et al. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics 2006;16:297-306.
34Gonçalo M, Coutinho I, Teixeira V, Gameiro AR, Brites MM, Nunes R, et al. HLA-B*58:01 is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population. Br J Dermatol 2013;169:660-5.
35Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 2005;102:4134-9.
36Tangamornsuksan W, Lohitnavy M. Association between HLA-B*1301 and dapsone-induced cutaneous adverse drug reactions: A Systematic review and meta-analysis. JAMA Dermatol 2018;154:441-6.
37Zhang FR, Liu H, Irwanto A, Fu XA, Li Y, Yu GQ, et al. HLA-B*13:01 and the dapsone hypersensitivity syndrome. N Engl J Med 2013;369:1620-8.
38Kano Y, Hiraharas K, Sakuma K, Shiohara T. Several herpesviruses can reactivate in a severe drug-induced multiorgan reaction in the same sequential order as in graft-versus-host disease. Br J Dermatol 2006;155:301-6.
39Wong YJ, Choo KJL, Soh JXJ, Tan CK. Cytomegalovirus (CMV) hepatitis: An uncommon complication of CMV reactivation in drug reaction with eosinophilia and systemic symptoms. Singapore Med J 2018;59:112-3.
40Mizukawa Y, Hirahara K, Kano Y, Shiohara T. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms severity score: A useful tool for assessing disease severity and predicting fatal cytomegalovirus disease. J Am Acad Dermatol 2019;80:670-800.
41Uhara H, Saiki M, Kawachi S, Ashida A, Oguchi S, Okuyama R. Clinical course of drug-induced hypersensitivity syndrome treated without systemic corticosteroids. J Eur Acad Dermatol Venereol 2013;27:722-6.
42Um SJ, Lee SK, Kim YH, Kim KH, Son CH, Roh MS, et al. Clinical features of drug-induced hypersensitivity syndrome in 38 patients. J Investig Allergol Clin Immunol 2010;20:556-62.
43Ushigome Y, Kano Y, Ishida T, Hirahara K, Shiohara T. Short- and long-term outcomes of 34 patients with drug-induced hypersensitivity syndrome in a single institution. J Am Acad Dermatol 2013;68:721-8.
44Descamps V, Ben Saïd B, Sassolas B, Truchetet F, Avenel-Audran M, Girardin P, et al. Management of drug reaction with eosinophilia and systemic symptoms (DRESS). Ann Dermatol Venereol 2010;137:703-8.
45Kuschel SL, Reedy MS. Cyclosporine treatment of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: A case report and brief review of the literature. Pract Dermatol 2018;2018:41-3.
46Kirchhof MG, Wong A, Dutz JP. Cyclosporine treatment of drug-induced hypersensitivity syndrome. JAMA Dermatol 2016;152:1254-7.
47Harman KE, Morris SD, Higgins EM. Persistent anticonvulsant hypersensitivity syndrome responding to ciclosporin. Clin Exp Dermatol 2003;28:364-5.
48Zuliani E, Zwahlen H, Gilliet F, Marone C. Vancomycin-induced hypersensitivity reaction with acute renal failure: Resolution following cyclosporine treatment. Clin Nephrol 2005;64:155-8.
49Ton A, Kassab L, Patel A, Dawson N. Severe acute hepatitis in drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome resolved following cyclosporine. J Allergy Clin Immunol Pract 2019. pii: S2213-2198(19)30592-6.
50Daoulah A, Alqahtani AA, Ocheltree SR, Alhabib A, Ocheltree AR. Acute myocardial infarction in a 56-year-old female patient treated with sulfasalazine. Am J Emerg Med 2012;30:638.e1-3.
51Bourgeois GP, Cafardi JA, Groysman V, Pamboukian SV, Kirklin JK, Andea AA, et al. Fulminant myocarditis as a late sequela of DRESS: Two cases. J Am Acad Dermatol 2011;65:889-90.
52Laban E, Hainaut-Wierzbicka E, Pourreau F, Yacoub M, Sztermer E, Guillet G, et al. Cyclophosphamide therapy for corticoresistant drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a patient with severe kidney and eye involvement and Epstein-Barr virus reactivation. Am J Kidney Dis 2010;55:e11-4.
53Oh HL, Kang DY, Kang HR, Kim S, Koh YI, Kim SH, et al. Severe cutaneous adverse reactions in Korean pediatric patients: A Study from the Korea SCAR registry. Allergy Asthma Immunol Res 2019;11:241-53.