Two cases of erythema exsudativum multiforme associated with Chlamydia pneumoniae infection

We report two cases of erythema exsudativum multiforme (EEM) that we concluded were caused by infections with Chlamydia pneumoniae. High titers of IgG antibody for Chlamydia pneumoniae were shown in the sera of both cases. One case showed the classical symptoms of pneumonia together with radiological changes in the chest; the other case did not show these symptoms. To the best of our knowledge, only three cases of erythema multiforme associated with Chlamydia pneumoniae infection have been reported.     

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.     

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.     

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.     

Mucositis Secondary to Chlamydia pneumoniae Infection: Expanding the Mycoplasma pneumoniae–Induced Rash and Mucositis Concept

The term Mycoplasma pneumoniae–induced rash and mucositis (MIRM) was recently proposed to identify the mucocutaneous condition secondary to M. pneumoniae infection that had historically been regarded among the more confusing pathologies of erythema multiforme and Stevens–Johnson syndrome. Based on a number of previous reports, these syndromes require differentiation since they have different prognoses and specific treatment requirements. We report a case of oral and genital erosions that strongly resembled MIRM without rash but were found to be secondary to a Chlamydia pneumoniae infection. After a thorough review of the literature on this subject, we propose that C. pneumoniae should also be considered a potential causative agent of MIRM and that this term should be amended to include C. pneumoniae infection.     

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。     

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。     

Erythema multiforme majus (Fuchs syndrome) associated with Mycoplasma pneumoniae infection in two patients

In Germany Fuchs syndrome is used to describe a variant of erythema multiforme majus which mainly involves the mucosal surfaces. As the skin may be completely unaffected, it is an under‐recognized diagnosis and often difficult to confirm. Clinical features involve erythema, erosions and ulcerations of the oral mucosa. In most cases there is severe conjunctivitis and sometimes the genital mucosa is involved. Most cases of Fuchs syndrome are triggered by infections; herpes simplex virus and Mycoplasma pneumoniae are the most common causes. We describe two women presenting with Fuchs syndrome after respiratory illness caused by Mycoplasma pneumoniae.     

Interpretation of Chlamydia trachomatis antibody response in chlamydial oculogenital infection.

OBJECTIVE--To study: (a) the chlamydial antibody response (to the D-K serovars) using the micro-immunofluorescence (micro-IF) test in the following groups: (I) chlamydial genital infection only, (II) chlamydial ocular infection only, (III) combined chlamydial ocular and genital infection (oculo-genital infection), (IV) chlamydial ocular infection with chlamydia-negative non-gonococcal urethritis, (V) adenovirus conjunctivitis (control group 1), (VI) male partners of group I-IV with no chlamydial oculogenital infection or non-gonococcal urethritis (control group 2) (b) the cross reactivity of antibodies in patients' sera between the three chlamydial species and within the serovars of C trachomatis in those with culture-positive chlamydial oculo-genital infection. SETTING--oculogenital (diagnostic) clinic at Moorfields Eye Hospital, London, UK. SUBJECTS--209 consecutive patients attending the clinic with Chlamydia trachomatis oculogenital infection and 86 patients with adenovirus conjunctivitis (control group 1) and 55 male partners with no evidence of chlamydial oculogenital infection or non-gonococcal urethritis (control group 2). RESULTS--Of all the patients with proven chlamydial oculogenital infection, 10.5% (22/209) and 94% (197/209) had IgM and IgG antibodies respectively. The geometric mean IgG antibody titres (GMT) were 1:98, 1:123, 1:245 and 1:101 in groups I to IV respectively. The IgG GMT values seen in control groups 1 and 2 were 1:45 and 1:36 respectively. Only 2/86(2%) patients in group V (control group 1) had IgG chlamydial antibodies of 1:32 and 1:64, whilst only 1/55(1.8%) and 4/55(7.3%) of patients in group VI(control group 2) had chlamydial IgG antibody titres of > or = 1:256 and > or = 1:128 respectively. A four-fold rise or fall in IgG antibody titre occurred in 56%(107/192) of patient groups I-IV over 2-6 weeks. Low titre cross-reactive antibody responses against different chlamydial species and serovars were commonly seen; 71%(148/209) of all patients showed cross-reactivity with Chlamydia pneumoniae or psittaci species or both, whilst 92% (193/209) of patients showed some level of cross reactivity to other pooled serovars of C trachomatis (A-C and L 1-3). CONCLUSIONS--Serological diagnosis of chlamydial infection as evidenced by a positive IgM antibody response, high IgG titre (> or = 1:256) or > or = 4-fold rise or fall in IgG antibody titre was seen in 78%(163/209) of patients with culture-positive chlamydial oculogenital infection. Chlamydial IgG antibody titres of > or = 1:256 had a sensitivity of 42.6%, specificity of 98.2%, positive predictive value of 98.8% and a negative predictive value of 31% for chlamydial infection at any site, when considering groups I-IV and control group 2. In this study of 216 patients with conjunctivitis, a positive IgG antibody response (titre > or = 1:16) had a sensitivity of 98.5%, specificity of 97.7%, positive predictive value of 98.5% and a negative predictive value of 97.7%, for chlamydial conjunctivitis. Patients with dual chlamydial infection of conjunctiva and genital tract had a higher IgG GMT titre than those with ocular or genital infection alone: infection at a second site may produce an anamnestic response. Although the micro-IF test is a useful adjunct for the diagnosis of chlamydial infection, cross-reactivity between different chlamydial species and serovars is common. Chlamydial seroepidemiological studies should be interpreted with caution, as studies may attribute a serological response to a particular species or serovar in a setting where two or more are prevalent.     

Persistent B-cell lymphopenia, multiorgan disease, and erythema multiforme caused by Mycoplasma pneumoniae infection

We report a 6-year-old girl in whom Mycoplasma pneumoniae infection presenting with erythema multiforme, multiorgan, and hematologic dysfunctions induced a long-standing, marked B-cell lymphopenia. An increase of CD8+ lymphocytes was also detected. We suggest that a selective cytotoxic T lymphocyte-dependent B cell lysis and the expansion of super-antigen activated CD8+ T cells may account for the multiorgan and hematologic disturbances triggered by M. pneumoniae.     

Acute infectious erythemas in children: a clinico-microbiological study

One-hundred children with an acute illness comprising fever and widespread erythematous rash were prospectively studied to determine whether clinical presentations are helpful in defining the causative agent and to identify the most appropriate microbiological specimens. An infectious agent was identified in 65 children; 72% were viruses, 20% were bacteria, 5% were Mycoplasma pneumoniae and in 3% both viruses and bacteria were detected. The most common infectious agents were picornaviruses, an atypical presentation of measles and Group A beta-haemolytic Streptococcus. Different patterns of rash occurred with each of these infections. The clinical presentation of a child with an acute febrile illness and rash was unhelpful in defining the causative agent. Routine management should include a throat swab for bacterial investigation and in selected cases a blood sample for IgM viral titres.     

Erythema multiforme associated with cytomegalovirus infection in nonimmunosuppressed patients.

BACKGROUND: It is widely known that cytomegalovirus (CMV) primarily brings about subclinical and asymptomatic infection in the early stages of life and can cause various dermatological and systemic disorders under immunosuppressed conditions. Nonimmunosuppressed individuals very rarely present with cutaneous CMV involvement. OBJECTIVE: In the present study, we described the clinical characteristics of 5 nonimmunosuppressed adult patients with positive IgM antibody to CMV. METHODS: The systemic symptoms and dermatological features of these 5 patients were described. Laboratory examinations including blood cell counts, liver and renal functions were performed. IgG and IgM antibodies to CMV were also examined at the first consultation and 2-3 months after the skin eruption. Polymerase chain reaction for CMV DNA was performed in the skin samples of the patients. RESULTS: All 5 patients had fever and complained of a sore throat. Multiple exudative erythema and target lesions with itching were observed mainly on the extremities. These symptoms and eruptions disappeared within 1 week after the onset and IgM antibody titers significantly decreased after 2-3 months. IgG antibody to CMV was already positive in 3 cases but was negative in 2 cases at the initial consultation. CONCLUSION: We propose that CMV infection may cause erythema multiforme by primary, recurrent infections or reactivation of CMV even in nonimmunosuppressed adults.     

Prospective case-control study of chlamydia, legionella and mycoplasma infections in patients with pityriasis rosea

A double-blind placebo-controlled trial reported the benefit of erythromycin in treating pityriasis rosea (PR), a postulated mechanism being the eradication of bacteria susceptible to erythromycin. The aim of this study was to investigate the association between PR and Chlamydia pneumoniae, C. trachomatis, Legionella longbeachae, L. micdadei, L. pneumophila, and Mycoplasma pneumoniae infections. We recruited 13 patients aged seven to 46 years (mean: 26.8 years) diagnosed to have PR in a primary care setting in 18 months. Lesional histopathology was arranged for atypical cases. Clotted blood was collected at initial presentation and four weeks later. Controls were 13 paired age-and-sex-matched patients requiring blood collection for non-dermatological diseases. Serology tests were performed in parallel but were read "blinded" on the acute and convalescent specimens of patients and the control subjects. The serology profiles were not diagnostic of active infection by any of the bacteria studied for all 13 patients. Two patients had four-fold increase in IgG titres against C. pneumoniae, with IgM being negative. Two patients had IgM detectable against L. pneumophila serotype 6 and M. pneumoniae respectively, with no significant rise of the specific IgG. These patients had no symptom or sign of chest infection. The seroprevalence and IgG titres of the study patients for the bacteria investigated were insignificantly different from those of control subjects. We conclude that the bacteria investigated in this study do not play a significant role in the pathogenesis of PR. We believe that anti-inflammatory and immunomodulatary effects might contribute towards the action of erythromycin, if any, in PR.     

Identification of herpes simplex virus DNA in lesions of erythema multiforme by the polymerase chain reaction.

An association between erythema multiforme and herpes simplex virus infection has been supported by clinical studies and by the detection by immunofluorescence of herpes viral antigen in sera and skin biopsy specimens of patients with erythema multiforme. In rare cases, the virus has also been isolated in cultures of skin biopsy specimens of erythema multiforme. To investigate further the association between erythema multiforme and herpes simplex virus, we used the polymerase chain reaction for herpes simplex virus to examine skin lesions from patients with erythema multiforme. In this study herpes simplex virus DNA was detected in 11 of 31 biopsy specimens of erythema multiforme; six additional cases showed equivocal amplification results, which is suggestive of low amounts of viral DNA. Seven skin and mucosal biopsy specimens with the histologic changes of herpes virus infection served as positive controls: all were positive for herpes simplex virus DNA. Viral DNA was not detected in control biopsy specimens from skin excised for unrelated conditions. These studies support the association of herpes simplex virus in the pathogenesis of some cases of erythema multiforme. The polymerase chain reaction provides a quick and effective method of detecting herpes simplex virus in lesions of herpes-associated erythema multiforme. Furthermore, the polymerase chain reaction may delineate those cases of erythema multiforme that are etiologically related to herpes virus infection and therefore might be treated with acyclovir to prevent recurrence.     

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.     

Prevalence of antichlamydial antibody in London blood donors.

The prevalence of type-specific antichlamydial antibody in a population of blood donors in London was studied using a microimmunofluorescence test. Twenty-six (17%) of 150 women and 38 (26%) of 150 men had antichlamydial antibody (IgG at greater than or equal to 1/16 or IgM greater than or equal to 1/8 or both). Of these, five (3%) women had one (0.75%) man had this antibody directed against Chlamydia trachomatis serotypes D-K, responsible for genital infections, and one man had antibody to Chlamydia psittaci agents. The remaining 57 men and women had antibody against an atypical chlamydial isolate designated Chlamydia IOL-207, which is iodine-negative and serologically distinct from both C trachomatis and C psittaci. The nature and location of infection by this agent are obscure. The results of this study suggest that the prevalence of sexually transmitted infection with C trachomatis serotypes D-K in a normal adult population in London is very low.     

Antichlamydial antibodies in pelvic inflammatory disease.

The role of Chlamydia trachomatis in pelvic inflammatory disease (PID) diagnosed without laparoscopy was assessed by measuring antichlamydial antibodies in the patient's serum and by comparing the results with those in patients with uncomplicated non-specific genital infection (NSGI) and gonorrhoea and in non-infected controls. A modified microimmunofluorescence test was used. Patients with severe PID had significantly more positive antichlamydial IgG and IgM results than did control subjects, patients with gonorrhoea, and patients with NSGI. Less severe PID was associated with significantly raised levels of antichlamydial IgG antibodies compared with NSGI and controls and with raised levels of IgM antibodies compared with controls. Two patients with PID had lower genital tract gonorrhoea, one of whom had raised antichlamydial antibody levels. These findings may indicate a mixed infection and therapy should be reviewed in such patients. A serological diagnosis of chlamydial infection is relatively easy and cheap and enables a rapid diagnosis of chlamydial infection to be made.     

Erythema Multiforme in a 25‐Day Old Neonate

Erythema multiforme is an acute, self‐limiting, mucocutaneous hypersensitivity reaction characterized by distinctive target lesions. Most cases have been attributed to infection. Erythema multiforme occurs mainly in young adults and is extremely rare during the neonatal period. We report a 25‐day‐old girl who presented with target skin lesions on both the palms and soles with no other associated symptoms. She had no remarkable maternal, birth, or past medical history. Complete blood count, urinalysis, chest radiography, and herpes simplex virus 1 and 2 immunoglobulin G (IgG) titers revealed no abnormalities. Pathologic examination showed vacuolar interface change and dyskeratotic cells in the epidermis consistent with erythema multiforme. This unusual case emphasizes the importance of recognizing diagnostic clues in examining patients. Even in the presence of uncharacteristic factors, the typical target lesions of erythema multiforme are distinctive.     

Antichlamydial antibodies in pelvic inflammatory disease

The role of Chlamydia trachomatis in pelvic inflammatory disease (PID) diagnosed without laparoscopy was assessed by measuring antichlamydial antibodies in the patient's serum and by comparing the results with those in patients with uncomplicated non-specific genital infection (NSGI) and gonorrhoea and in non-infected controls. A modified microimmunofluorescence test was used. Patients with severe PID had significantly more positive antichlamydial IgG and IgM results than did control subjects, patients with gonorrhoea, and patients with NSGI. Less severe PID was associated with significantly raised levels of antichlamydial IgG antibodies compared with NSGI and controls and with raised levels of IgM antibodies compared with controls. Two patients with PID had lower genital tract gonorrhoea, one of whom had raised antichlamydial antibody levels. These findings may indicate a mixed infection and therapy should be reviewed in such patients. A serological diagnosis of chlamydial infection is relatively easy and cheap and enables a rapid diagnosis of chlamydial infection to be made.     

女性生殖道沙眼衣原体持续感染的现状

生殖道沙眼衣原体感染在人群中的发生率高,特别在年轻女性人群中,容易导致持续性的生殖道感染,进而引起一系列严重并发症(如不孕不育).感染的严重程度取决于沙眼衣原体本身的致病力大小、环境因素及宿主易感因素.筛检沙眼衣原体持续性感染的最佳血清学指标是其IgG和C反应蛋白(两者同时阳性),而IgG只能作为其既往感染的血清学指标.