Case Of Chronic Mucocutaneous Candidiasis Research Articles

Patients with STAT1 Gain-of-function Mutations Display Increased Apoptosis which is Reversed by the JAK Inhibitor Ruxolitinib

IntroductionThe signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is characterized by a broader clinical phenotype that may include bacterial, viral, or invasive fungal infections, autoimmunity, autoinflammatory manifestations, vascular complications, or malignancies. The severity of lymphopenia may vary and influence the infectious morbidity.MethodsIn our cohort of seven STAT1-GOF patients, we investigated the mechanisms that may determine T lymphopenia, we characterized the interferon gene signature (IGS) and analyzed the effect of ruxolitinib in reverting the immune dysregulation.ResultsSTAT1-GOF patients exhibited increased T lymphocyte apoptosis that was significantly augmented in both resting conditions and following stimulation with mitogens and IFNα, as evaluated by flow cytometry by Annexin V/ Propidium iodide assay. The JAK inhibitor ruxolitinib significantly reduced the IFNα-induced hyperphosphorylation of STAT1 and reverted the stimulation-induced T-cell apoptosis, in vitro. In two adult STAT1-GOF patients, the JAKinib treatment ameliorated chronic mucocutaneous candidiasis and lymphopenia. Most STAT1-GOF patients, particularly those who had autoimmunity, presented increased IGS that significantly decreased in the two patients during ruxolitinib treatment.ConclusionIn STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations.

Chronic mucocutaneous candidiasis and rheumatoid arthritis in autoimmune polyendocrinopathy

Chronic mucocutaneous candidiasis is a heterogeneous group of disorders characterized by early-onset chronic recurrent mucocutaneous infections with Candida albicans. It is associated with several endocrinopathies such as hypoparathyroidism, hypoadrenalism, and hypogonadism with or without other autoimmune diseases such as vitiligo, alopecia areata, pernicious anemia, and hepatitis. Here, we describe a case of chronic mucocutaneous candidiasis with polyendocrinopathy with unusual presentations and rheumatoid arthritis.

A novel case of chronic mucocutaneous candidiasis: Overlap between autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy syndrome and hyper IgE syndrome

Chronic mucocutaneous candidiasis (CMC) is a clinical entity where extensive fungal infection of skin, hair, nail, and mucosa with Candida sp. is seen. It has got association with several immunological and endocrinal dysfunctions. We report a case of a 14-year-old boy who presented with peculiar facies, gross failure to thrive, fungal granulomatous lesions with scaring alopecia, oropharyngeal candidiasis, ectodermal dystrophy, grade 3 clubbing of all four limbs, interstitial keratitis with leukoma due to recurrent corneal ulcerations, and persistent deciduous teeth. A diagnosis of CMC was made and evaluation of immunological pathways revealed a high titer of immunoglobulin E. CMC with overlapping features of autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome and hyper IgE syndrome is extremely rare in literature. Timely diagnosis of an underlying etiology and proper treatment of a case of CMC may provide a better quality of life of the patient.

Recurrent Vulvovaginal Candidiasis: Could It Be Related to Cell-Mediated Immunity Defect in Response to Candida Antigen?

Recurrent vulvovaginal candidiasis (RVVC) is a common cause of morbidity affecting millions of women worldwide. Patients with RVVC are thought to have an underlying immunologic defect. This study has been established to evaluate cell-mediated immunity defect in response to candida antigen in RVVC cases. Our cross-sectional study was performed in 3 groups of RVVC patients (cases), healthy individuals (control I) and known cases of chronic mucocutaneous candidiasis (CMC) (control II). Patients who met the inclusion criteria of RVVC were selected consecutively and were allocated in the case group. Peripheral blood mononuclear cells were isolated and labeled with CFSE and proliferation rate was measured in exposure to candida antigen via flow cytometry. T lymphocyte proliferation in response to candida was significantly lower in RVVC cases (n=24) and CMC patients (n=7) compared to healthy individuals (n=20, <0.001), but no statistically significant difference was seen between cases and control II group (P>0.05). Family history of primary immunodeficiency diseases (PID) differed significantly among groups (P=0.01), RVVC patients has family history of PID more than control I (29.2 vs. 0%, P=0.008) but not statistically different from CMC patients (29.2 vs. 42.9%, P>0.05). Prevalence of atopy was greater in RVVC cases compared to healthy individuals (41.3 vs. 15%, P=0.054). Lymphoproliferative activity and vaginal symptoms were significantly different among RVVC cases with and without allergy (P=0.01, P=0.02). Our findings revealed that T cells do not actively proliferate in response to Candida antigen in some RVVC cases. So it is concluded that patients with cell-mediated immunity defect are more susceptible to recurrent fungal infections of vulva and vagina. Nonetheless, some other cases of RVVC showed normal function of T cells. Further evaluations showed that these patients suffer from atopy. It is hypothesized that higher frequency of VVC in patients with history of atopy might be due to allergic response in mucocutaneous membranes rather than a functional impairment in immune system components.

P193 A case of chronic mucocutaneous candidiasis due to a stat1 mutation

P193 A case of chronic mucocutaneous candidiasis due to a stat1 mutation

A case of chronic mucocutaneous candidiasis caused by STAT1 gain-of-function mutation and literature review

Objective To summarize the clinical characteristics, diagnosis and treatment of chronic mucocutaneous candidiasis(CMC). Methods The case diagnosed as CMC in the Department of Nephrology and Immunology of Shenzhen Children's Hospital in February 24, 2014 was analyzed in terms of symptoms, signs, laboratory findings, gene tests and treatment process, and related literature was reviewed. Results The patient was a 14-year-old boy.The patient started to develop recurrent oral candida infection shortly after birth, then candida infection of skins and nails, which could be alleviated by antifungal agents, but easily relapsed.Since 4 years ago, autoimmune reactions such as autoimmune anemia, thrombocytopenia, leucopenia, proteinuria, and hypothyroidism had successively appeared, and cytopenia began to palliate after administering Glucocorticoid and Cyclosporin, but easily relapsed when the dosage was reduced.The genetic test showed the case was of signal transducer and activator of transcription 1(STAT1) gain-of-function mutation.During the hospitalization, hemophagocytic syndrome (HPS) and stagnation of hematopoietic function successively occurred.The cytopenia did not improve and the patient suffered severe infection in spite of washing red blood cells 13 times and blood palate 3 times via infusion, together with high dosage of Dexamethasone and Cyclosporine.The peripheral blood cells and bone marrow gradually returned to normal after being treated by human granulocyte colony-stimulating factor combined with Dexamethasone and Cyclosporin.Retrieving the database in PubMed database, 824 articles were found which were about CMC, and 39 of them were about the STAT1 gain-of-function mutation, including 120 cases.But there was only 1 domestic case in 2012, who was a three-year-old child, manifesting recurrent fungal infection of the skin. Conclusions STAT1 gain-of-function acquired mutation is one of the reasons that can lead to CMC.Autoimmune reactions prominently represented by cytopenia occur in a few patients with CMC.It should be alert on those who are with CMC and simultaneously with autoimmune reaction of blood system.And gene tests facilitate the early diagnosis. Key words: Chronic mucocutaneous candidiasis; Anemia; Hemophagocytic syndrome; Signal transducer and activator of transcription 1; Granulocyte colony-stimulating factor

STAT1変異による慢性粘膜皮膚カンジダ症の1例

STAT1変異による慢性粘膜皮膚カンジダ症の1例

Autosomal Dominant Cases of Chronic Mucocutaneous Candidiasis Segregates with Mutations of Signal Transducer and Activator of Transcription 1, But Not of Toll-Like Receptor 3

We report a family with autosomal dominant chronic mucocutaneous candidiasis as well as recurrent viral infections that segregate with a novel signal transducer and activator of transcription 1 (STAT1) mutation. Prophylactic treatment with fluconazole and immunoglobulin replacement has been initiated, with good clinical response.

Mukokutane Candida-Infektionen

Infection with the yeast candida is a quite common disease. Its occurrence might be harmless, however, Candida infections often present with an underlying systemic disease. Thus, candidiasis in some cases can be considered as an indicator for e.g. diabetes mellitus or immune deficiency (i.e. HIV or leukaemia). Of note, we have to distinguish the colonisation and the infection with Candida because only the presence of the yeast together with clinical symptoms is an indication for treatment. The latter has to be adapted according to age, localisation and potentially underlying systemic disease. A special form of Candidiasis constitutes the chronic mucocutaneous candidiasis which can occur in line with hereditary immune deficiencies or also isolated. In the present review we discuss the current status of diagnostic and therapy of mucocutaneous candidiasis as well as the (patho-) immunologic background of yeast infections using the example of a special case of chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis; report of three cases with different phenotypes.

Chronic Mucocutaneous Candidiasis (CMCC) refers to a group of immunodeficiencies, characterized by persistent or recurrent infections of the skin, nails, and mucus membranes caused by candida. A wide range of immunologic abnormality has been reported in CMCC. Defects in cellular limb of the immune system, mainly the specific response to antigens of candida species, are well documented in CMCC patients. A subgroup of patients is predisposed to development of autoimmune endocrinopathies. These patients need repeated monitoring of endocrine functions. Immunologic studies are needed to identify the extent of immunodeficiency and other abnormalities of immune functions. We report three cases of CMCC. These patients show different phenotypes and highlight the need for complete evaluation and long term follow-up for accompanying disorders.

Cerebral vasculitis in chronic mucocutaneous candidiasis: Autopsy case report

An autopsy case of chronic mucocutaneous candidiasis (CMCC) is reported here, in which cerebral vasculitis developed in the final stage. A 32‐year‐old man who had suffered from superficial candidial infection since his childhood was diagnosed as having CMCC. During the past 7 years the patient had developed various associated disorders including insulin‐dependent diabetes mellitus (IDDM), common variable immunodeficiency (CVID), candidial esophagitis, multiple digestive tract ulcers and pyothorax. In 1998, at the age of 32, he developed convulsions that were accompanied by impairment of consciousness, and which were temporarily treated with steroid pulsed‐medication. Epileptic status associated with widespread cerebral infarctions occurred subsequently, however, and the patient died of sepsis 2 months later. At autopsy, multiple cerebral infarctions and arterial thrombosis were evident. These were histologically proven to be primary vasculitis which was confined solely to the brain, and this was verified by general pathological examination. Thus, some as yet unknown cerebrovascular factors might be involved in the onset of an autoimmune‐related vasculitis in patients with a longstanding immunodeficiency state such as CMCC.

乳児期より発生した慢性皮膚粘膜カンジダ症の１例

乳児期より発生した慢性皮膚粘膜カンジダ症の１例

Allogenic Bone Marrow Transplantation for a Case of Chronic Mucocutaneous Candidiasis

Allogenic Bone Marrow Transplantation for a Case of Chronic Mucocutaneous Candidiasis

A case of chronic mucocutaneous candidiasis successfully treated with ketoconazole.

A case of chronic mucocutaneous candidiasis successfully treated with ketoconazole.

TRIPLE FUNGAL INFECTION—CHRONIC MUCOCUTANEOUS CANDIDIASIS, EXOPHYTIC DERMATOPHYTOSIS AND CRYPTOCOCCAL MENINGITIS: A NEW AND UNUSUAL COMBINATION—

The clinical and immunological studies of an unusual case of chronic mucocutaneous candidiasis (CMCC) are reported. An 18-year-old male with life-long CMCC was superinfected by a dermatophyte showing exophytic clinical features in his childhood. In addition he has suffered from fatal cryptococcal meningitis since the age of 18. The combination of three fungi, i.e., Candida albicans, Trichophyton mentagrophytes and Cryptococcus neoformans, has not been found in an examination of the literature. The author's hypothesis, "immune deviation theory" in the pathogenesis of CMCC, is presented in detail. The possible role of hypovitaminosis A anddisorder of iron metabolism in CMCC and treatment of CMCC are reviewed briefly.

Transfer Factorが奏効した慢性皮膚粘膜カンジダ症

4才女児の角質増殖性皮疹をともなう慢性皮膚粘膜カンジダ症(CMCC)にtransfer factor(TF)を用い, 著明な改善をえた。投与前後の免疫状態にも変化がみられた。TFによるCMCCの治療について文献的に考察した。CMCCのすべての例にTFが有効であるわけではないが, 奏効する場合の効果は劇的である。今後さらに検討すべき治療法である。

Dermatophilus congolensis Chronic Nodular Disease in Man

Dermatophilus congolensis is a common infectious agent among animals. However, infectivity in man has only rarely been observed. We report the association of D. congolensis with a chronic nodular disease in an 8-year-old boy. The time of exposure to the organism was unknown but may have occurred in utero. Testing of the immunologic system reveals a deficiency of B-lymphocytes bearing Fc receptors as well as impairment of lymphokine production. It is possible that an immunologic deficiency has permitted a chronic infestation with D. congolensis in a manner similar to that described for some cases of chronic mucocutaneous candidiasis.

Transfer factor in the treatment of a case of chronic mucocutaneous candidiasis

A girl with a severe case of chronic mucocutaneous candidiasis in whom a partial defect in cell-mediated immunity to C. albicans was demonstrated is described. Chemotherapy with anti-Candida agents afforded only temporary clinical improvement. Although her delayed hypersensitivity skin test response to C. albicans was consistently negative, her lymphocytes underwent blast transformation when cultured in the presence of C. albicans and other mitogens. The addition of exogenous transfer factor to the culture medium increased her lymphocyte blast transformation response to C. albicans. Because of these findings she was treated with transfer factor with the aim of restoring expression of cutaneous hypersensitivity to the antigen, and providing her with clinically significant immunity to the antigen. Following a course of repeated injections of transfer factor given in conjunction with a short course of intravenous amphotericin B, her infection cleared and she has had no recurrence of infection for at least 6 months.

THYMIC TRANSPLANTATION IN A CASE OF CHRONIC MUCOCUTANEOUS CANDIDIASIS

A 17-year-old male with chronic mucocutaneous candidiasis, Addison's disease, pernicious anaemia, and malabsorption complicated by multiple B-vitamin deficiencies was transplanted twice with fetal thymic tissue. Previously negative in-vitro blastogenic response to candida became positive within one week of the first transplant and was restored to normal by the second transplant. A positive candida skin test was seen for the first time in 4 years. The patient's clinical condition has improved and there has been clearing of oral candidal lesions and increased ability to mount a vigorous inflammatory response.