Erythema multiforme due to Mycoplasma pneumoniae infection in two children

Mycoplasma pneumoniae is an important and highly relevant cause of bullous erythema multiforme, isolated mucositis, and Stevens-Johnson syndrome in children. In this article, we present two children with respiratory Mycoplasma pneumoniae infection and associated cutaneous findings within the spectrum of erythema multiforme. We review the literature associating these three entities with Mycoplasma pneumoniae infection and discuss controversies regarding the classification of erythema multiforme, as well as update reported infectious causes of the bullous form. Many understand the erythema multiforme spectrum to include bullous erythema multiforme, mucositis, and Stevens-Johnson syndrome in the order of increasing severity. We feel that this relationship should be reconsidered to help better understand the prognosis and outcomes. It is our opinion that bullous erythema multiforme is a separate, yet related condition that can occur in the context of Mycoplasma pneumoniae infection. With many similarities to mucositis and Stevens-Johnson syndrome, bullous erythema multiforme can be considered part of a spectrum of disease that includes Stevens-Johnson syndrome. Unlike mucositis and Stevens-Johnson syndrome, bullous erythema multiforme caused by Mycoplasma pneumoniae infection has low morbidity for the child. Mycoplasma pneumoniae-associated mucositis and Stevens-Johnson syndrome seem to occur along a spectrum with separate prognosis and potential pathogenesis compared with bullous erythema multiforme. Making the distinction between these conditions is valuable for predicting the child's prognosis. Patients who develop symptoms consistent with these conditions should be appropriately evaluated for Mycoplasma pneumoniae infection and closely monitored.     

Stevens-Johnson syndrome associated with Mycoplasma pneumoniae infection

The Stevens-Johnson syndrome is a relatively uncommon, severe form of erythema multiforme. A case is presented in which Mycoplasma pneumoniae infection was established as the causative agent. Clinicians need to be aware of this uncommon association. We emphasize the need to consider M. pneumoniae infection as one of the many agents responsible for the Stevens-Johnson syndrome.     

Fuchs Syndrome Associated with Mycoplasma pneumoniae (Stevens–Johnson Syndrome without Skin Lesions)

Abstract: Stevens–Johnson syndrome is a severe mucocutaneous disease following drugs or infections. We present a 7‐year‐old boy with mucous membrane lesions (stomatitis, conjunctivitis, and urethritis) but without skin lesions. The diagnosis of acute Mycoplasma pneumoniae infection strongly suggests a concomitant Fuchs syndrome.     

无皮疹型Stevens-Johnson综合征四例

目的报道4例无皮疹型Stevens-Johnson综合征，并对该病有关文献进行综述。方法对4例患者的发病因素、临床特征及治疗进行较为系统地观察。结果4例均为儿童，表现有发热，口唇黏膜肿胀、糜烂、出血性渗出和坏死，3例有结膜炎症，其中2例出现睑结膜纤维素样渗出；4例都无明显皮肤损害。3例进行了肺炎支原体抗体和冷凝集试验检测，肺炎支原体抗体IgG全部阳性．冷凝集试验仅l例阳性，为1：128（正常低于1：32）。2例入院前诊断“化脓性扁桃体炎”．其中l例发疹时抗链球菌溶血素O试验1240IU／mL阳性（正常低于200IU／mL）。2例柯萨奇病毒IgM检测阳性。单用抗生素治疗无效．对糖皮质激素治疗敏感，4例均痊愈。结论无皮疹型Stevens—Johnson综合征的预后较好，其病因仍以感染为主，尤其是肺炎支原体、病毒感染更应加以重视。     

Stevens-Johnson syndrome associated with Mycoplasma pneumoniae infections

The Stevens-Johnson syndrome is a multisystem inflammatory disorder associated with a widespread erythematous eruption that can result in death. Although usually considered a pediatric disease, this syndrome frequently affects adults. There are many etiologic associations including drugs and infections; however, the pathophysiology of the syndrome remains obscure. Treatment at present is symptomatic and supportive. Although frequently used, the beneficial role of corticosteroids in this syndrome remains to be proved. The case report describes a young woman who after treatment with several drugs developed the Stevens-Johnson syndrome in association with a Mycoplasma pneumoniae infection. We include a brief review of the literature with emphasis on the Stevens-Johnsons syndrome's association with M pneumoniae infections. Those caring for patients with skin disease should be aware of the association between such treatable infections and this syndrome.     

STEVSENS-JOHNSON SYNDROME ASSOCIATED WITH MYCOPLASMA PNEUMONILAE INFECTION

SUMMARY.— Two cases of Stevens-Johnson syndrome associated with pneumonia, in which high titres to Mycoplasma pneumoniae were present, are described. In one case M. pneumoniae was isolated from the sputum.     

Mycoplasma pneumoniae and mucositis - part of the Stevens-Johnson syndrome spectrum

Background: Mycoplasma pneumoniae may induce mucosal inflammation, referred to as M. pneumoniae-associated mucositis (MPAM). There is no generally accepted definition of MPAM, since there may be mucosal lesions only, or mucosal and minimal skin lesions. Patients and Methods: We conducted a literature review of MPAM, paying particular attention to pathogenesis, clinical manifestations, treatment decisions, and prognosis. Results: We identified 32 cases of MPAM (median age 13.5 years), whereof 23 patients were otherwise healthy children and young adolescents (72%). M. pneumoniae infection was associated with fever and respiratory symptoms in all calls; it was confirmed by serology (n = 30) and/or PCR (n = 9). Oral lesions were present in all cases, followed by ocular (97%) and uro-genital lesions (78%). Despite the syndrome's name postulating the absence of cutaneous involvement, minimal skin lesions occurred in 31%. Treatment regimens included systemic antibiotics (100%) and systemic anti-inflammatory treatment with corticosteroids (31%) or immunoglobulins (9%). Macrolides were given in 81%, with failure, relapse, and/or worsening in one-third of patients. No patient suffered long-term sequelae. Conclusion: MPAM is a distinct extra-pulmonary manifestation falling into the continuum of Stevens-Johnson syndrome. This entity may be due to inflammatory mechanisms suggesting that systemic anti-inflammatory treatment is even more important than antimicrobials.     

Erythema multiforme majus and Chlamydia pneumoniae infection

BACKGROUND: Erythema multiforme majus of infectious origin is an acute eruptive syndrome seen more commonly in young subjects and characterised by an appearance of round target lesions. In most cases, it is associated with infection involving Herpes simplex virus or Mycoplasma pneumoniae. We report an original case of erythema multiforme majus subsequent to infection with Chlamydia pneumoniae. CASE REPORT: An 18 year-old man was hospitalised for management of generalised skin rash comprising lesions in rings, associated with bullous and post-bullous lesions, chiefly in the oral (preventing eating) and genital areas in a setting of febrile cough. Various bacterial agents (Mycoplasma pneumoniae, Chlamydia pneumoniae) and viral agents were suspected, but serological testing for Chlamydia pneumoniae alone was positive with IgM of 128 IU and IgG of 64 IU. The outcome was favourable within several days following administration of symptomatic treatment (rehydration, mouthwashes, etc.) and aetiological treatment (acyclovir: 30 mg/kg/d, ofloxacine: 400 mg/d). At D15, serologic tests for Mycoplasma pneumoniae continued to be negative. Anti-Chlamydia pneumoniae IgM and IgG were 256 IU. At D30, IgM was 128 IU while IgG remained at 256 IU. DISCUSSION: The existence of a systematic skin rash comprising typical target lesions and mucosal lesions in the oral and genital areas suggested to us a diagnosis of erythema multiforme majus. Screening for the agents generally responsible was negative and drug-induced rash was ruled out. Serological tests for Chlamydia pneumoniae were positive at various times, resulting in diagnosis of erythema multiforme majus secondary to infection with Chlamydia pneumoniae. Following demonstration of the presence of Chlamydia pneumoniae using reliable methods and the elimination of other causes of erythema multiforme majus, dermatologists should opt for this aetiology in order to optimise treatment.     

Stevens-Johnson syndrome as an unusual adverse effect of azithromycin

Stevens-Johnson syndrome mostly involves the skin and mucous membranes. The diagnosis is made when the characteristic rash appears 1 to 3 weeks after exposure to a known stimulus and cannot be explained by some other diagnosis. A 62-year-old woman was admitted for evaluation of toxo-allergic dermatitis and collagenosis. Ten days prior to admission she was taking a course of azithromycin for upper respiratory tract infection. After a few days she was feeling better but maculopapular, erythematous rash developed over her palms, accompanied by fever and chills as well as reddish discoloration around her eyes. Within the next few days the rash progressed to the feet. Routine hematologic, biochemical and immunologic studies did not confirm the diagnosis of inflammatory rheumatic disease. Corticosteroid therapy with methylprednisolone (1 mg/kg) for the presumed Stevens-Johnson syndrome was started and her condition improved in several days; she became afebrile and her skin lesions gradually disappeared. There is only one report, in a child, documenting the association of Stevens-Johnson syndrome with azithromycin, as in this patient.     

Mycoplasma pneumoniae-Associated Mucositis with Minimal Skin Manifestations

Mycoplasma pneumoniae-associated mucositis is a rarely described complication of M. pneumoniae infection presenting with ocular, oral, and genital involvement but without the typical skin lesions seen in Stevens-Johnson syndrome. A 27-year-old man with a past history of asthma presented at the emergency room with a 1-week history of cough (initially non-productive but subsequently associated with non-bloody mucopurulent sputum), fever, myalgias, headache, and progressive dyspnea. Two days before admission he had commenced amoxicillin/clavulanic acid with no improvement. The patient reported bilateral conjunctival injection and hemorrhagic ulcers on the lips commencing the day prior to admission. Physical examination revealed fever (39 degrees C), bilateral exudative conjunctivitis, painful hemorrhagic ulcers on the lips, tongue, and oral mucosa, small scrotal erosions, erythema of the penile meatus, and small erythematous bullae on the dorsum of each hand; subsequently, the patient developed bullae at the venipuncture site on his right arm. Laboratory tests revealed positive IgM serology for M. pneumoniae, with titer elevation. The patient was successfully treated with levofloxacin and prednisolone. Our case appears to be the first adult patient described with M. pneumoniae-associated mucositis, which has previously been reported only in pediatric patients. This is also the first reported instance of a case of M. pneumoniae-associated mucositis treated with levofloxacin and prednisolone. M. pneumoniae infection should be considered in all cases of mucositis, and treatment of this condition with levofloxacin and prednisolone seems to be effective.     

Toxic epidermal necrolysis. Clinical findings and prognosis factors in 87 patients

Eighty-seven patients with toxic epidermal necrolysis were observed at H?pital Henri Mondor in Créteil, France, over the last 12 years. The mean percentage of body surface area involved was 39%. Erosive mucous membrane lesions, identical to those of Stevens-Johnson syndrome, were present in all but three cases. Necrolysis was sometimes generalized within 24 hours but usually spread progressively after a Stevens-Johnson syndrome-like aspect at the onset. Mortality was 25%. Infection, mainly with Staphylococus aureus and Pseudomonas aeruginosa, was the first cause of death, clearly responsible in ten of 20 cases. Age, extension of necrolysis, idiopathic nature of toxic epidermal necrolysis, ingestion of many drugs, elevation of urea, creatinine, and glucose levels, neutropenia, lymphopenia, and thrombocytopenia were statistically linked to a bad prognosis. A multivariant analysis showed that three of these prognosis factors are of paramount importance, namely: age, area of necrolysis, and serum urea level. Pigmentary changes and sicca syndrome were frequently observed sequelae in survivors.     

Paraneoplastic pemphigus with bronchiolitis obliterans in a child

Paraneoplastic pemphigus (PNP) is a rare blistering autoimmune disease associated with an underlying neoplasm, mucous membrane erosions, and occasionally bronchiolitis obliterans. Most cases have been reported in adults and the number of childhood cases in the current literature is limited. We describe a young patient with PNP who was initially misdiagnosed as having recurrent Stevens-Johnson syndrome. This patient had an underlying inflammatory myofibroblastic tumor and subsequently developed fatal progressive bronchiolitis obliterans.     

Gianotti-Crosti syndrome in an adult following recent Mycoplasma pneumoniae infection

A 44-year-old insulin-dependant diabetic woman presented with a pruritic papular eruption involving her hands, forearms and elbows. One week prior to the eruption, the patient had an upper respiratory tract infection and had taken oral ibuprofen 400 mg q.i.d. p.r.n. Skin biopsy revealed histological features consistent with Gianotti-Crosti syndrome. Serology was consistent with recent Mycoplasma pneumoniae infection and past Epstein-Barr viral infection. Her liver function tests were deranged and serum protein electrophoresis showed two sharp discrete monoclonal immunoglobulin bands. The eruption resolved completely 15 days after onset. Her serum protein studies and liver function tests subsequently normalized and she had no recurrences of her cutaneous eruption. It was concluded that the patient had Gianotti-Crosti syndrome associated with Mycoplasma pneumoniae infection.     

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Are Severity Variants of the Same Disease which Differs from Erythema Multiforme

A new classification, based on the pattern and distribution of cutaneous lesions, separates erythema multiforme major from Stevens-Johnson syndrome. A retrospective reclassification of 76 cases supported the validity of that separation by demonstrating differing causes and pathology. Another prospective international case-control study found differing demographic characteristics and risk factors between erythema multiforme major on the one hand and Stevens-Johnson syndrome or toxic epidermal necrolysis on the other. Erythema multiforme major was mainly related to Herpes virus infection, while Stevens-Johnson syndrome and toxic epidermal necrolysis were associated with drug reactions.     

Stevensjohnson Syndrome Caused by a Health Drink (Eberu®) Containing Ophiopogonis Tuber

Stevens-Johnson syndrome is considered to be a severe type of erythema exsudativum multiforme. It is characterized by erythema with bullous and eroded lesions of skin and mucous membranes. We report a case of Stevenjohnson syndrome following consumption of a health drink containing ophiopogonis tuber. A 66-year-old female took an O.T.C. health drink for fever. The next morning, she noted erythema and swelling of her face, neck, and chest. She started to develop bullous and eroded lesions on the skin of her entire body and the mucous membranes of her oral cavity, conjunctiva, and cornea, and she became feverish. She had high degrees of corneal erosion and liver dysfunction. Skin biopsy showed diffuse necrosis of the epidermis. After admission to the hospital, steroid pulse therapy (1000 mg/day of methylprednisolone sodium succinate) was continued for 5 days. The health drink induced a positive drug lymphocyte stimulation test (DLST) and patch test. A challenge test was done with a one hundredth dose, and it was positive. We did patch tests with all components of the drink and found that Mai-Meu-Dong-Tang (ophiopogonis) alone was positive at 72 hours. There is no previous report of Stevens-Johnson syndrome caused by a health drink or Mai-Meu-Dong-Tang. Even though it is a health drink, we should be aware of the possibility of a severe reaction.     

肺炎支原体诱导的皮疹和黏膜炎8例临床特征及预后分析

【摘要】 目的 分析肺炎支原体诱导的皮疹和黏膜炎（MIRM）的临床特征及预后。方法 调阅中山大学附属第一医院2004年11月至2021年5月出院诊断为多形红斑/重症多形红斑或Stevens-Johnson综合征患者的资料,以MIRM诊断标准筛选出其中的MIRM患者,且排除了其他病因,分析其临床表现、实验室和辅助检查、治疗和预后。结果 8例符合MIRM诊断,其中男4例,女4例,发病年龄4 ~ 30（15.63 ± 9.16）岁。8例均有发热,其中5例有咳嗽、咽痛等上呼吸道前驱症状。所有患者均有口腔黏膜损害,其中5例有口唇血痂;7例有眼损害,表现为结膜充血及分泌物增多。所有患者均有皮损,表现为靶形损害5例、水疱4例。所有患者血清学肺炎支原体IgM均阳性。1例反复出现干咳等上呼吸道感染,每次发作与肺炎支原体感染密切相关,取外周血行全外显子测序显示,NLRC4和IRGM杂合突变。3例患者行皮损组织病理检查,符合多形红斑。7例系统使用糖皮质激素治疗,6例静脉注射免疫球蛋白,5例阿奇霉素,5例使用阿昔洛韦或伐昔洛韦或利巴韦林。平均随访2.9年,3例痊愈,1例失明,1例反复出现干咳和口腔溃疡及四肢皮疹,余3例分别出现眼睑板腺功能障碍、泪点狭窄及角膜上皮损害等眼部损害。结论 MIRM好发于儿童及年轻成人,多有发热、咽痛、咳嗽等前驱症状,黏膜损害明显,部分有皮肤靶形损害。多数患者单次发病后痊愈,个别反复发作者可能与自身炎症相关基因和感染相关基因突变有关。     

Stevens-Johnson syndrome associated with brucella infection

Abstract:  Stevens-Johnson syndrome is a potentially fatal condition that manifests mainly on the skin and mucosal surfaces but also affects other vital organs. There are no report of Stevens-Johnson syndrome caused by brucella infection in the literature. In this article, a previously healthy boy, diagnosed as Stevens-Johnson syndrome associated with brucella infection, is reported.     

Correlations between clinical patterns and causes of erythema multiforme majus,Stevens-Johnson syndrome,and toxic epidermal necrolysis: results of an international prospective study

BACKGROUND: It was proposed that Stevens-Johnson syndrome and toxic epidermal necrolysis differed from erythema multiforme majus by the pattern and localization of skin lesions. OBJECTIVE: To evaluate the validity of this clinical separation. DESIGN: Case-control study. SETTINGS: Active survey from 1989 to 1995 of 1800 hospital departments in Europe. PATIENTS: A total of 552 patients and 1720 control subjects. METHODS: Cases were sorted into 5 groups (erythema multiforme majus, Stevens-Johnson syndrome, Stevens-Johnson syndrome-toxic epidermal necrolysis overlap, toxic epidermal necrolysis, and unclassified erythema multiforme majus or Stevens-Johnson syndrome) by experts blinded as to exposure to drugs and other factors. Etiologic fractions for herpes and drugs obtained from case-control analyses were compared between these groups. RESULTS: Erythema multiforme majus significantly differed from Stevens-Johnson syndrome, overlap, and toxic epidermal necrolysis by occurrence in younger males, frequent recurrences, less fever, milder mucosal lesions, and lack of association with collagen vascular diseases, human immunodeficiency virus infection, or cancer. Recent or recurrent herpes was the principal risk factor for erythema multiforme majus (etiologic fractions of 29% and 17%, respectively) and had a role in Stevens-Johnson syndrome (etiologic fractions of 6% and 10%) but not in overlap cases or toxic epidermal necrolysis. Drugs had higher etiologic fractions for Stevens-Johnson syndrome, overlap, or toxic epidermal necrolysis (64%-66%) than for erythema multiforme majus (18%). Unclassified cases mostly behaved clinically like erythema multiforme. CONCLUSIONS: This large prospective study confirmed that erythema multiforme majus differs from Stevens-Johnson syndrome and toxic epidermal necrolysis not only in severity but also in several demographic characteristics and causes.     

Indapamide-associated Stevens-Johnson syndrome.

Stevens-Johnson syndrome is an acute, inflammatory eruption of the skin and mucous membranes often associated with drug ingestion. A forty-five-year-old woman showed symptoms consistent with Stevens-Johnson syndrome two days after indapamide therapy was begun for the treatment of hypertension. Initial manifestations consisted of headaches, sore throat, cough, and symptoms of conjunctival injection, including redness and swelling. Approximately two weeks later, the patient noted skin eruptions involving the conjunctiva, lips, face, neck, trunk, and extremities. She was treated with cool compresses, antiseptics, ophthalmic antibiotics and steroids, and oral prednisone. Symptoms began to resolve approximately eight days after indapamide was discontinued and treatment was begun. Although rare, Stevens-Johnson syndrome should be considered in the differential diagnosis of a patient with a history of indapamide ingestion who presents with malaise, fever, and skin eruptions.     

Bullous erythema multiforme following herpes zoster and varicella-zoster virus infection

Four cases of herpes zoster-induced bullous erythema multiforme (EM) are reported. Three patients presented with widespread skin lesions 10 to 14 days after an episode of thoracic herpes zoster. In these patients a high increase in varicella-zoster virus (VZV) antibody titer was detected, indicating secondary VZV infection. Histologic examinations of skin biopsy from a patient with widespread lesions (case 4) revealed a mixture of EM, toxic epidermal necrolysis and herpetic virus infection. VZV should be included in the list of infectious agents able to trigger EM and Stevens-Johnson syndrome.