Akiba H, Motoki Y, Satoh M, Iwatsuki K, Kaneko F
Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka-1, Fukushima, 960-1295 Japan.
Eur J Dermatol. 2001 Jan-Feb;11(1):58-62.
Although deep trichophytic infection often occurs in immunocompromised patients, the immune deficiency in such patients has not been clarified. A 28-year-old man who suffered from recalcitrant trichophytic granuloma and tinea universalis during treatment for SLE with corticosteroid is described here to define the immunological abnormalities. In addition to routine immunological tests, we evaluated the patient's innate and specific immune functions to dermatophytes, including T cell, natural killer (NK) cell and neutrophil functions and activation of the complement cascade. We measured the minimum inhibitory concentration (MIC) of itraconazole for the isolated fungus and its concentrations in the patient's serum and pus. Trichophyton (T.) rubrum was constantly isolated from the exudates of the patient's skin lesions, although the concentrations of itraconazole in his serum (198 ng/ml) and lesions (210 ng/ml) were sufficient to inhibit the growth of the isolated fungus in vitro. Specific cell-mediated immune responses, determined by T cell stimulation and IFN-gamma production, were evoked following stimulation with trichophytic antigens. The patient's innate immunity, assessed by activation of the complement cascade and neutrophil-mediated phagocytosis, was not impaired. The number of circulating NK cells was markedly decreased (0.2% of the peripheral blood mononuclear cells), and was associated with low NK cell activity against K-562 cells even though lymphopenia had improved. The deficiency of innate immunity mediated by NK cells might be responsible for a part of the persistence of trichophytic granuloma in our case. Dermatophytes usually affect the horny layer of the skin and do not invade the living layers because the host immune system uses various mechanisms to eliminate the fungi. Both specific T cell-mediated immunity and nonspecific immunological mechanisms provide host defense against fungal infections. An adaptive immune response is usually preceded by innate immune responses mediated by neutrophils, NK cells, and circulating proteins such as complement components and anti-microbial peptides. However, in patients with localized or systemic immunological defects, granulomatous cutaneous infection of dermatophytes mostly caused by trichophytic fungi may occur [1]. Trichophytic granuloma includes Majocchi's granuloma [2] and disseminated trichophytic granuloma [3]. Recently, we experienced a patient with trichophytic granuloma and tinea universalis caused by Trichophyton (T.) rubrum infection during treatment with corticosteroid for systemic lupus erythematosus (SLE). We describe the clinical details of this patient, focusing on his immunological defects which led to the persistence of the fungal infection.
虽然深部毛癣菌感染常发生于免疫功能低下的患者，但此类患者的免疫缺陷尚未明确。本文描述了一名28岁男性，他在接受皮质类固醇治疗系统性红斑狼疮（SLE）期间，患有顽固性毛癣菌肉芽肿和泛发性体癣，以明确其免疫异常情况。除常规免疫检测外，我们评估了患者针对皮肤癣菌的固有免疫和特异性免疫功能，包括T细胞、自然杀伤（NK）细胞和中性粒细胞功能以及补体级联反应的激活情况。我们测定了伊曲康唑对分离出的真菌的最低抑菌浓度（MIC）及其在患者血清和脓液中的浓度。尽管患者血清（198 ng/ml）和皮损（210 ng/ml）中的伊曲康唑浓度足以在体外抑制分离出的真菌生长，但从患者皮肤病变渗出物中持续分离出红色毛癣菌。在用毛癣菌抗原刺激后，通过T细胞刺激和γ干扰素产生所确定的特异性细胞介导免疫反应被激发。通过补体级联反应激活和中性粒细胞介导的吞噬作用评估的患者固有免疫未受损。循环NK细胞数量明显减少（占外周血单个核细胞的0.2%），尽管淋巴细胞减少有所改善，但仍与针对K-562细胞的低NK细胞活性相关。在我们的病例中，由NK细胞介导的固有免疫缺陷可能是毛癣菌肉芽肿持续存在的部分原因。皮肤癣菌通常影响皮肤角质层，不会侵入活组织层，因为宿主免疫系统会利用各种机制清除真菌。特异性T细胞介导的免疫和非特异性免疫机制均为宿主提供针对真菌感染的防御。适应性免疫反应通常先于由中性粒细胞、NK细胞以及循环蛋白如补体成分和抗菌肽介导的固有免疫反应。然而，在局部或全身免疫缺陷的患者中，可能会发生主要由毛癣菌引起的皮肤癣菌肉芽肿性皮肤感染[1]。毛癣菌肉芽肿包括马约基肉芽肿[2]和播散性毛癣菌肉芽肿[3]。最近，我们遇到一名在接受皮质类固醇治疗系统性红斑狼疮（SLE）期间因红色毛癣菌感染引起毛癣菌肉芽肿和泛发性体癣的患者。我们描述了该患者的临床细节，重点关注导致真菌感染持续存在的免疫缺陷。
