Syndrome d’hypersensibilité médicamenteuse en pratique interniste : pièges diagnostique et thérapeutique.Huit observationsDrug-induced hypersensitivity syndrome (DIHS): diagnostic and therapeutic traps. Eight case reports.

Purpose.– Drug-induced hypersensitivity syndrome (DIHS) is an acute and severe drug reaction. Manifestations include severe skin lesions, fever, nodal enlargement, blood eosinophilia and multisystemic involvement. The severe systemic manifestations of DIHS are responsible for a 10% mortality rate. The pertinence of corticosteroid therapy is discussed.Methods. – The authors report eight retrospective cases of DIHS obtained from the PMSI (Programme de Médicalisatiopn des Systèmes d'Information) between November 1991 and November 1998.Results.– The series consisted of five male and three female patients (mean age: 52.6 years; range: 23–83 years). The interval between the introduction of the drug and the onset of the reaction varied from two to eight weeks. Due to severe systemic manifestations, three patients were given corticosteroid therapy. Healing of skin and systemic disorders resolved with a mean delay of 4.4 weeks (range: 1 to 56 weeks).Conclusion.– DIHS can be a diagnostic trap, as there are no diagnostic criteria for DIHS. Only the association of multiple arguments such as the time to the occurrence of symptoms, clinical similarity to many infectious illnesses, hypereosinophilia, atypical lymphocytosis, etc. may help guide diagnosis. DIHS can also be a therapeutic trap, as prompt withdrawal of the offending drug is essential to minimize morbidity. Although still controversial in the literature, the pertinence of corticosteroid therapy may be discussed in case of severe systemic effects. Patch testing can be a valuable tool to determine the responsibility of a drug; however it proves to be useful only when positive.     

Drug-induced hypersensitivity syndrome associated with a marked increase in anti-paramyxovirus antibody titers in a scleroderma patient.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe multiorgan hypersensitivity reaction that usually appears after prolonged exposure to certain drugs and may be related to reactivation of herpes viruses. There have been few reports regarding the clinical association of DIHS with pathogens other than herpes viruses. CASE SUMMARY: We report a case of scleroderma with DIHS associated with paramyxovirus infection. A 61-year-old man with early diffuse cutaneous scleroderma with myositis and progressive interstitial pneumonia developed generalized erythema with high fever 3 weeks after taking sulfamethoxazole/trimethoprim. The diagnosis of DIHS was made based on the patient's history of using an offending drug, clinical manifestations and laboratory data showing peripheral eosinophilia with the presence of atypical lymphocytes. Virological tests showed significant increases of antibody titers against mumps virus and parainfluenza virus type 2, which strongly suggested that paramyxovirus infection occurred during the clinical course of DIHS. DISCUSSION: These findings suggest that paramyxovirus infection had contributed to the development of DIHS in this patient and that there is a need to seek evidence of other viral infections in some cases of DIHS, especially those without herpes virus reactivation/infection.     

Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses.

A relationship between viral infections and the simultaneous or subsequent development of allergic inflammation has often been observed in various clinical situations. Recent studies suggest an intimate relationship between reactivations of herpesviruses including human herpesvirus 6 (HHV-6) and the development of a severe systemic hypersensitivity reaction referred to as drug-induced hypersensitivity syndrome (DIHS).This syndrome has several important clinical features that cannot be solely explained by drug antigen-driven oligoclonal expansion of T cells: they include paradoxical worsening of clinical symptoms after discontinuation of the causative drug. In view of the similarity to GVHD or immune reconstitution syndrome (IRS) in clinical manifestations and emergence of viral infections, the clinical symptoms observed during the course of DIHS and GVHD are likely to be mediated by antiviral T cells that can cross-react with the drug and alloantigens, respectively. In considering common intrinsic properties of the causative drugs to potentially induce immunosuppression, reconstitution of a valid immune response to these viruses, which is typically observed in IRS, may be the most crucial process that takes place after withdrawal of the causative drug in patients with DIHS. Thus, this syndrome should be regarded as a reaction induced by a complex interplay among several herpesviruses (EB virus, HHV-6, HHV-7, and cytomegalovirus), antiviral immune responses, and drug-specific immune responses. This review includes discussion of the pathomechanism, the clinical symptoms, laboratory findings, pathological findings and therapy.     

Recurrent Churg-Strauss vasculitis. With exophthalmos, hearing loss, nasal obstruction, amyloid deposits, hyperimmunoglobulinemia E, and circulating immune complexes

Churg-Strauss vasculitis in remission for 4 1/2 years recurred, with new, previously undescribed features, after a lapse in corticosteroid therapy. Bilateral exophthalmos, unilateral hearing loss, and nasal obstruction accompanied fever, severe asthma, and palpable purpura. Leukocytosis with eosinophilia, an elevated ESR, hyperimmunoglobulinemia E, an pulmonary infiltrates were seen again. Circulating immune complexes were detected, and microamyloid deposits were found in the conjunctiva and skin. All clinical and laboratory manifestations responded to corticosteroid therapy. Monitoring the levels of IgE may add a diagnostic and prognostic feature to the classification of necrotizing vasculitides.     

Adult-onset Still's disease

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology and pathogenesis. AOSD is a rare condition, usually presenting with high fever accompanied by systemic manifestations. The disease is a heterogeneous pathological entity with a range of etiologies, manifestations and prognosis. There is no single diagnostic test for AOSD; rather, the diagnosis is based upon clinical criteria such as arthralgia, fever, skin rash, lymphadenopathy, and hepatosplenomegaly. Determination of the procalcitonin level and the biological response to empirical corticosteroid therapy generally helps the diagnosis, while immune-serology, as a 'screening' test, will not add meaningful information in most cases. Treatment consists of anti-inflammatory medications. Non-steroid anti-inflammatory drugs have limited efficacy, corticosteroid therapy and disease-modifying antirheumatic drugs are usually required. Novel therapeutic approaches, such as anti-tumor necrosis factor blockade and stem cell transplantation, are promising. In this chapter we present clinical and laboratory parameters of 18 patients diagnosed with AOSD at our institution between 1997 and 2003, and review the literature.     

DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome after sulfasalazine and carmazepine: report of two cases]

INTRODUCTION: To better individualize drug hypersensitivity reaction, Bocquet et al. have recently called this adverse drug reaction DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). EXEGESIS: We report two cases of DRESS and highlight the main characteristics of this syndrome. Two patients presented severe febrile skin eruption following drug intake (carbamazepine or sulfazalazine), with hypereosinophilia and hepatitis. All symptoms resolved after drug withdrawal and corticosteroid therapy. DRESS syndrome is an idiosyncratic reaction characterised by febrile eruption, occurring 2 to 6 weeks after the beginning of the treatment, accompanied by systemic symptoms and biological abnormalities (hypereosinophilia, hepatitis). Some complications can occur. This syndrome can be fatal. Numerous drugs can be responsible for this reaction to medication. The physiopathology has not yet been elucidated, and the treatment is not codified, but the triggering agent must immediately be stopped. Corticotherapy is sometimes used. CONCLUSION: It is important to recognize this entity recently named DRESS syndrome because it can mimic other pathologies, is potentially serious, and because withdrawal of the incriminating drug is imperative.     

Is the drug-induced hypersensitivity syndrome (DIHS) due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review

Background  

Drug-Induced Hypersensitivity Syndrome (DIHS) is a severe and rare systemic reaction triggered by a drug (usually an antiepileptic drug). We present a case of DISH and we review studies on the clinical features and treatment of DIHS, and on its pathogenesis in which two elements (Herpesvirus infection and the drug) interact with the immune system to trigger such a syndrome that can lead to death in about 20% of cases.     

Drug-induced scleroderma-like lesion

Drug-induced scleroderma-like lesion is a condition in which administration of a drug induces skin sclerotic lesions similar to systemic sclerosis or morphea. The clinical manifestations of drug-induced scleroderma-like lesion can be divided into two types: scleroderma-like lesions and morphea-like plaques. A wide variety of drugs can cause drug-induced scleroderma-like lesion. Bleomycin, _L-tryptophan, vinyl chloride, and phytonadione (vitamin K₁) have been reported, but in recent years, cases due to chemotherapeutic agents, such as taxane-based agents, gemcitabine, and tegafur-uracil, and immune checkpoint inhibitors have increased. Drug-induced scleroderma-like lesion differs from systemic sclerosis in that it does not include Raynaud's phenomenon, nail-fold capillary abnormality, organ involvement, such as reflux esophagitis, interstitial pneumonia, renal crisis, or anti-nuclear Abs. On the other hand, there are reports of cases in which Raynaud's phenomenon, positive conversion of anti-nuclear Abs, and development of skin sclerosis from the fingers developed after initiation of the drug. Whether the skin sclerosis improves after discontinuation of the drug depends on the patient. In patients with severe skin sclerosis, functional impairment, such as flexion contracture of the fingers, may occur, and systemic therapy, such as steroids, may be necessary. When treating patients with skin sclerosis, it is important to keep in mind the possibility that the sclerotic lesion may be induced by a drug.     

Management of severe skin disorders in sarcoidosis

Sarcoidosis is a systemic granulomatous condition of unknown origin. It is defined by histological features of epithelioid and giant-cell granuloma without caseous necrosis. Skin manifestations are observed in 25% of the cases of sarcoidosis, sometimes appearing as the inaugural symptom. Although these skin disorders are not life threatening, they do have a major functional and/or esthetic impact and may require specific therapy using aggressive treatments. Recent progress in immunology and molecular biology is helpful in understanding interactions between monocyte-macrophages and T lymphocytes and the cytokine pattern implicated in the granulomatous reaction. Research concerning the agent(s) causing the focus of the immune response on the TH1 pathway may be helpful in developing promising immunomodulation therapies. The very unpredictable course of the disease explains the difficulties encountered in assessing therapeutic efficacy and the small number of controlled trials. General corticosteroid therapy remains the mainstay treatment for severe skin disorders in sarcoidosis. APS and local corticoid therapy can be useful when systemic corticosteroids are not needed or to achieve a steroid-sparing effect. Indications for methotrexate and new compounds such as thalidomide or certain antibiotics with an immunomodulator effect remain to be evaluated.     

Single center prospective study of tacrolimus efficacy and safety in the treatment of various manifestations in systemic lupus erythematosus

The aim of this study was to prospectively evaluate the efficacy and safety of tacrolimus (TAC) in various manifestations of systemic lupus erythematosus (SLE) patients in daily clinical practice. Each of the 21 TAC-treated patients with SLE in our care over 2 years was enrolled in this open-label trial. Patients were administered TAC at a dosage of 1–6 mg once daily, followed up for 24 weeks. Efficacy and safety were evaluated utilizing clinical and laboratory findings. As treatment targets, TAC was preferentially used with oral corticosteroid administration for mild active manifestations such as arthritis, skin eruptions, or asymptomatic nephritis. In efficacy, the mean value of the SLE disease activity index was significantly reduced to 4.1, 2.7, 1.8, and 1.2 (N = 21, 20, 16 and 13) at 0, 4, 12, and 24 weeks, respectively. In eight cases, treatment was discontinued within 24 weeks due to insufficient effects (6 cases) and side effects (2 cases). Non-serious side effects were observed in only five cases (23.8%) over 24 weeks. TAC can be considered both effective and safe for the treatment of various manifestations of SLE.     

Drug-induced hypersensitivity syndrome with rapid hematopoietic reconstitution during treatment for acute myeloid leukemia

Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe life-threatening, drug-induced, systemic hypersensitivity reaction. We report two patients who developed DIHS during treatment for acute myeloid leukemia. Awareness of DIHS is necessary when systemic eruptions and high fever occur in leukemic patients, especially with rapid hematopoietic recovery after chemotherapies.     

DRESS-Syndrom nach Sulfasalazintherapie

A female patient developed systemic rash, lung edema, electrocardiogram (ECG) abnormalities and fulminant hepatitis with partial liver failure 4 weeks after the start of sulfasalazine treatment. Peripheral T-cell activation, a positive PCR test for human herpesvirus (HHV) 6 as well as eosinophilia in bronchial lavage and a differential blood count were also present. After initiation of systemic corticosteroid therapy and cessation of accompanying medication the clinical symptoms and abnormal laboratory test levels were gradually resolved. A DRESS syndrome (drug rash with eosinophilia and systemic symptoms) was confirmed in accordance with the diagnostic criteria.     

Rapid appearance of severe mitral regurgitation under high-dosage corticosteroid therapy in a patient with systemic lupus erythematosus

Survival of patients with systemic lupus erythematosus has increasedwith corticosteroid therapy. However, adverse effects of corticosteroidtherapy on cardiovascular structures, such as scarring and shrinkingof affected valves, are not well known. We report the case ofa 19-year-old patient who developed severe mitral insufficiencywithin a few weeks after high-dosage corticosteroid therapyhad been instituted for an acute relapse of systemic lupus erythematosus.The rapid development of severe mitral regurgitation was documentedby sequential colour Doppler echocardiography.     

Localization of extrapulmonary tuberculosis in the synovial membrane,skin, and meninges in a patient with systemic lupus erythematosus and IgG deficiency

We report on a 31-year-old female patient with systemic lupus erythematosus (SLE) for 24 years who had a past history of skin tuberculosis (lupus vulgaris), long-term corticosteroid therapy, and IgG deficiency. She presented with monoarthritis and concomitant meningitis from skin tuberculosis after 5 years. The diagnosis of joint and meningeal tuberculosis was defined with clinical symptoms--signs and typical histopathological findings of involved synovium. Clinical improvement was achieved with antituberculous therapy. Cutaneous, articular, and cerebral manifestations of tuberculosis might have been confused with some of the lupus manifestations or lupus activation. It should be kept in mind that tuberculosis may be encountered in SLE due to the nature of the underlying disease and/or its therapy. It is also worth mentioning that, in this patient, tissues involved with extrapulmonary tuberculosis were the primary areas of involvement with SLE.     

Churg-Strauss综合征肺损害1例并文献复习

目的 加深对Churg-Strauss综合征又名变应性肉芽肿血管炎(CSS)的认识.方法 通过对1例CSS病例的诊断、治疗及相关文献进行研究学习,分析Churg-Strauss综合征的病因、临床症状、实验室检查、影像学表现、诊断、鉴别诊断及治疗.结果 CSS病因不清,临床表现无特异性,可累及多系统器官,最常见的临床表现是哮喘及血管炎引起的肺部表现,特征性的病理表现为外周血嗜酸粒细胞增多,目前治疗首选激素,预后较好.结论 Churg-Strauss综合征是一种少见的系统性血管炎,临床缺乏特异性表现,易被误诊,当患者表现为哮喘、外周血嗜酸性粒细胞增多及肉芽肿性血管炎时,应高度怀疑此病.     

Skin manifestations of herpesvirus infections

Currently there are eight human herpesviruses identified that cause disease in both adults and children. Although the manifestations of disease differ with each herpesvirus, cutaneous presentations are common among almost all of them. These skin manifestations may be visually similar among several of these viruses, occasionally making it challenging to diagnose the patient’s illness. Laboratory diagnostic testing is commercially available for most of these viruses. Because many herpesvirus infections are self-limiting in immunocompetent hosts, patients require only supportive care. Effective antiviral therapy is available for the more severe cases of infection caused by herpes simplex virus (HSV), varicella zoster virus (VZV), or cytomegalovirus (CMV). Healthcare practitioners should become familiar with the different cutaneous manifestations these viruses may exhibit.     

A case of drug-induced hypersensitivity syndrome with multiple organ involvement treated with plasma exchange

A 53-year-old male patient began treatment for systemic exanthema with diaphenylsulfone (DHS) on 21 November 2002. On 18 December 2002, the patient developed a fever and additional systemic erythematous exanthema. Systemic lymphadenopathy, hepatosplenomegaly, leukocytosis (in particular, an increase in the number of atypical lymphocytes) and liver dysfunction followed. After cessation of the DHS treatment on 25 December 2002, acute renal failure occurred and the patient was transferred to Shinshu University Hospital on 4 January 2003. The patient was diagnosed with drug-induced hypersensitivity syndrome (DIHS). Steroid pulse therapy (methylprednisolone 1000 mg/day for 3 days) was given, followed by 60 mg/day of prednisolone. The patient's renal functions recovered and he was taken off hemodialysis therapy. However, the patient relapsed twice despite two sessions of steroid pulse therapy and an increase in the dose of prednisolone to 100 mg/day. Plasma exchange (PE) was carried out to reduce the activity of the disease. With a total of four plasma exchanges, we were able to reduce the dose of prednisolone from 100 mg/day to 60 mg/day without relapse. There were no adverse effects from the plasma exchanges. Plasma exchange should be considered in the treatment with corticosteroid-resistant DIHS with multiple organ lesions.     

Syndrome de Sweet médicamenteux à l’hydroxychloroquine : à propos de 2 cas

IntroductionHydroxychloroquine is widely prescribed in systemic lupus erythematosus. Dermatologic adverse drug reactions are rare but can mimic a disease specific manifestation of lupus. Exceptionally, Sweet's syndrome, or acute febrile neutrophilic dermatosis, may be drug-induced.Case reportsTwo patients aged 31 and 42 years were treated with hydroxychloroquine for systemic lupus and Sjogren's syndrome, respectively. Three weeks after starting treatment, they had a febrile, purple and erythematous papular rash of the trunk and limbs. There was a biological inflammatory syndrome and skin biopsy disclosed an infiltrate of the dermis rich in neutrophils. Lesions regressed after stopping hydroxychloroquine and introducing systemic corticosteroid therapy. Allergologic tests discussed the differential diagnosis with a delayed-type hypersensitivity reaction.ConclusionWe report two exceptional cases of drug-induced Sweet's syndrome related to hydroxychloroquine treatment in autoimmune rheumatic diseases.     

Cryoglobulinemic vasculitis resistant to intermittent intravenous pulse cyclophosphamide therapy

We report on a 78-year-old patient with severe disease manifestations including polyneuropathy and clinically suspected secondary temporal arteritis due to hepatitis C virus-associated cryoglobulinemic vasculitis (CV). Despite intermittent intravenous pulse cyclophosphamide therapy and oral corticosteroid therapy her condition further deteriorated. Only oral cyclophosphamide therapy with high-dose corticosteroid and plasmapheresis was efficient in inducing a remission of her CV. This case report demonstrates that pulse cyclophosphamide therapy may not be sufficient to control severe manifestations of cryoglobulinemic vasculitis.     

Severe restrictive pulmonary defect in a patient with adult-onset Still's disease

Adult-onset Still's disease is characterized by seronegative arthritis, fever, and an evanescent skin rash. Earlier reports have described pneumonitis and pleuritis as manifestations of this disease. We report a patient with adult-onset Still's disease with severe restrictive ventilatory impairment and evidence of respiratory muscle weakness who responded to corticosteroid and aspirin therapy.