The immune reconstitution syndrome (IRS) is an increasingly recognized disease concept and is observed with a broad-spectrum of immunosuppressive therapy-related opportunistic infectious diseases and severe drug eruptions complicated by viral reactivations. Clinical illness consistent with IRS includes tuberculosis, herpes zoster, herpes simples, cytomegalovirus infections and sarcoidosis: thus, the manifestations of this syndrome and diverse and depend on the tissue burden of the preexisting infectious agents during the immunosuppressive state, the nature of the immune system being restored, and underlying diseases of the hosts. Although IRS has originally been reported to occur in the setting of HIV infection, it has become clear that the development of IRS can also be in HIV-negative hosts receiving immunosuppressive agents, such as prednisolone and tumor necrosis factor α inhibitors, upon their reduction and withdrawal. Drug-induced hypersensitivity syndrome, a life-threatening multiorgan system reaction, is another manifestation of the newly observed IRS. Clinical recognition of the IRS is especially important in improving the outcome for diseases with an otherwise life-threatening progenosis. Clinicians should be aware of the implications of IRS and recognize that relieving the symptoms and signs of immune recovery by anti-inflammatory therapies needs to be balanced with anti-microbial therapies aiming at reducing the amplitude and duration of tissue burden of preexisting microbes.

Detection of HSV DNA in saliva is a useful and noninvasive, quantitative method for establishing the role of HSV in the pathogenesis of PV and for identifying individuals at greater risk for subsequently developing refractory PV.

It remains unknown why the occurrence of eczema herpeticum (EH) caused by an extensive disseminated cutaneous infection with HSV-1 or HSV-2 is associated with the exacerbation of atopic dermatitis lesions after withdrawal of treatment. Although regulatory T cells (Tregs) limit the magnitude of HSV-specific T cell responses in mice, their role in the induction and resolution of EH has not been defined. We initially investigated the frequencies, phenotype, and function of Tregs in the peripheral blood of atopic dermatitis with EH (ADEH) patients at onset and after clinical resolution, atopic dermatitis patients without EH, and healthy controls. Tregs with the skin-homing phenotype and the activated/induced phenotype were expanded at onset and contracted upon resolution. Treg-suppressive capacity was retained in ADEH patients and, the expanded Tregs suppressed IFN-γ production from HSV-1–specific CD8+ and CD4+ T cells. The increased frequency of CD14dimCD16+ proinflammatory monocytes (pMOs) was also observed in the blood and EH skin lesions. Thus, pMOs detected in ADEH patients at onset were characterized by an increased ability to produce IL-10 and a decreased ability to produce proinflammatory cytokines, unlike their normal counterparts. Our coculture study using Tregs and pMOs showed that the pMOs can promote the expansion of inducible Tregs. Tregs were detected frequently in the vicinity of HSV-expressing and varicella zoster virus–expressing CD16+ monocytes in the EH lesions. Expansions of functional Tregs, together with pMOs, initially required for ameliorating excessive inflammation occurring after withdrawal of topical corticosteroids could, in turn, contribute to the initiation and progression of HSV reactivation, resulting in the onset of EH.

No abstract

Mycoplasma pneumoniae (Mp) is one of the most common causes of community-acquired pneumonia. It can induce a cellular immune response, leading to respiratory inflammation and injury. Mp infection is frequently accompanied by a variety of extrapulmonary manifestations, including arthritis, hepatitis, myositis, neurological involvement and cutaneous diseases. Cutaneous diseases, such as erythema nodosum, erythema multiforme, urticaria, vasculitis and Stevens-Johnson syndrome (SJS), develop in up to 25-33% of all Mp infections (1, 2). SJS associated with Mp infection is commonly observed in children, while adult SJS is caused mainly by drugs (3). Adult SJS associated with Mp infection has seldom been reported (4, 5). Here, we report 2 adult SJS patients with Mp infection and drug reaction, with possible synergistic effects on the development of SJS. CASE REPORTSPatient 1. A 33-year-old man visited our hospital with ocular and oral lesions. He had a high-grade fever, general fatigue and nasal discharge, for which he had been prescribed diclofenac and L-carbocisteine by his doctor one day after the appearance of symptoms. On the following day, he had a painful throat and eyes, and was admitted to our hospital. Physical examination revealed hyperaemic conjunctivae, corneal erosions and pseudomembranous formation. Erosions on the buccal mucosa and ulcerations on the lips were also observed. No cutaneous lesions were seen. Laboratory tests revealed leukocytes 13.3×10 9 /l and C-reactive protein (CRP) 7.1 mg/dl (normal < 0.3). Liver function tests were within normal limits. Human immunodeficiency virus (HIV) infection was negative and no adenovirus antigen was detected in the conjunctivae. Herpes simplex virus (HSV) antigen on the lip was negative. On admission, a titre of particle agglutination (PA) test for Mp was 1:320 (normal < 40). No abnormal findings were seen on chest X-ray. A skin specimen could not be obtained because the patient declined biopsy of the labial lesions. Atypical SJS without appearance of skin lesions was suspected. Lymphocyte transformation test (LTT) was performed to identify culprit drugs on admission (6, 7). The LTT for diclofenac was positive (stimulation index level 2.56 (positive >1.80)). The patient was treated with oral prednisolone, 40 mg daily, and a glucocorticoid eye drop. The prednisolone was tapered gradually. A 4-fold reduction in PA titre was found 4 weeks after onset. Patient 2.A 59-year-old man was referred to our hospital because of a high-grade fever and mucosal lesions. He had been treated with loxoprofen and clarithromycin for fever and sore throat for 4 days before presentation. The symptoms persisted and he noticed labial and oral lesions. On examination, his temperature was 40°C, and bilateral conjunctivitis with pseudomembranous formation, corneal erosions (Fig. 1A), haemorrhagic appearance of the lips, and erosions on the buccal mucosa (Fig. 1B) were observed. Erosions were seen on the glans penis. Several scattered macules with bullae were also observed on the trunk an...