Progress in molecular diagnosis and treatment of chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membrane. It is a rare and severe disease resulting from autoimmune defects or immune dysregulations. Nonetheless, the diagnosis and treatment of CMC still pose significant challenges. Erroneous or delayed diagnoses remain prevalent, while the long-term utility of traditional antifungals often elicits adverse reactions and promotes the development of acquired resistance. Furthermore, disease relapse can occur during treatment with traditional antifungals. In this review, we delineate the advancements in molecular diagnostic and therapeutic approaches to CMC. Genetic and biomolecular analyses are increasingly employed as adjuncts to clinical manifestations and fungal examinations for accurate diagnosis. Simultaneously, a range of therapeutic interventions, including Janus kinase (JAK) inhibitors, hematopoietic stem cell transplantation (HSCT), cytokines therapy, novel antifungal agents, and histone deacetylase (HDAC) inhibitors, have been integrated into clinical practice. We aim to explore insights into early confirmation of CMC as well as novel therapeutic options for these patients.

Deep dermatophytosis caused by Trichophyton rubrum in an elderly patient with CARD9 deficiency: A case report and literature review.

Deep dermatophytosis is an invasive and sometimes life-threatening fungal infection mainly reported in immunocompromised patients. However, a caspase recruitment domain-containing protein 9 (CARD9) deficiency has recently been reported to cause deep dermatophytosis. Herein, we report the first Japanese case of deep dermatophytosis associated with CARD9 deficiency. An 80-year-old Japanese man with tinea corporis presented with subcutaneous nodules on his left sole. Histopathological findings revealed marked epithelioid cell granulomas with filamentous fungal structures in the deep dermis and subcutis, and the patient was diagnosed with deep dermatophytosis. Despite antifungal therapy, the subcutaneous nodule on his left sole gradually enlarged, his left calcaneal bone was invaded, and the patient finally underwent amputation of his left leg. Genetic analysis revealed a homozygous CARD9 c.586 A > G (p. Lys196Glu) variant, suggesting a CARD9 deficiency. Here, we discuss the clinical features of CARD9 deficiency-associated deep dermatophytosis with a case report and review of the literature.

Malignant Transformation and Treatment Recommendations of Chronic Hyperplastic Candidiasis-A Six-year Retrospective Cohort Study.

BACKGROUND: Oral chronic hyperplastic candidiasis (CHC) is the most uncommon type of oral candidiasis with diverse manifestations. Up to date the diagnosis, long-term management and prognosis of this oral potentially malignant disorder remain obscure. OBJECTIVES: The aim of this study was to provide the recommendations guiding the diagnostic procedure, clinical management and prognosis assessment of CHC. METHODS: A retrospective cohort study was performed during January 2015 to April 2021 involving patients with a definite diagnosis of CHC in the Department of Oral Medicine of Peking University School and Hospital of Stomatology. Demographic features, clinical and histopathological features, treatment protocols and follow-ups including malignancy transformation were analysed. RESULTS: Fourty eight CHC patients were collected and reviewed, with a male-to-female ratio of 2.69:1. The average age at diagnosis was 54.92 ± 9.79 (36-80) years old. Clinically, the multiform oral lesions were diverse and frequently presented as white plaque and erythematous lesions. As a result, the initial diagnostic accordance rate was only 54.17%, and the most common presumptive initial diagnoses were oral lichen planus (22.92%), oral leukoplakia (20.83%) and traumatic lesion (2.08%). Histopathologically, ten (20.83%) patients had varying degrees of epithelial dysplasia, and two (4.17%) patients had malignant transformation with a mean transformation time of 6.5 ± 6.36 months. Among the 28 patients who underwent fungal culture, 24 patients were exclusively infected by Candida albicans, with two patients each mixed infected by C glabrata and C tropicalis, respectively. Notably, treatment with fluconazole had the lower recurrence rate compared with topical nystatin. CONCLUSIONS: The diagnosis and management of CHC remain a challenge due to its polymorphic clinical presentations, chronic progression and potential of malignant transformation.

Primary immunodeficiency and chronic mucocutaneous candidiasis: pathophysiological, diagnostic, and therapeutic approaches.

Chronic mucocutaneous candidiasis (CMC) is characterized by a chronic or recurrent non-invasive infection, mainly due to Candida albicans, in skin, nails, and mucous membranes, associated in some cases with autoimmune manifestations. The key immune defect is a disruption of the action of cytokine IL-17, whose most common genetic etiology is STAT1 gene gain-of-function (GOF) mutations. The initial appropriate treatment for fungal infections is with azoles. However, the frequent occurrence of drug resistance is the main limitation. Therefore, identification of the underlying inborn error if immunity in CMC may allow to widen therapeutic options aimed at restoring immunological function. Type I and II Janus kinase-inhibitors have been shown to control CMC in cases associated with STAT1 GOF. In this review, we delve into the pathogenesis of CMC and the underlying immune mechanisms. We describe the reported genetic defects in which CMC is the main manifestation. Diagnostic and therapeutic approaches for these patients are also offered.

Human STAT1 Gain-of-Function Heterozygous Mutations: Chronic Mucocutaneous Candidiasis and Type I Interferonopathy.

Heterozygous gain-of-function (GOF) mutations in STAT1 in patients with chronic mucocutaneous candidiasis (CMC) and hypothyroidism were discovered in 2011. CMC is the recurrent or persistent mucocutaneous infection by Candida fungi, and hypothyroidism results from autoimmune thyroiditis. Patients with these diseases develop other infectious diseases, including viral, bacterial, and fungal diseases, and other autoimmune manifestations, including enterocolitis, immune cytopenia, endocrinopathies, and systemic lupus erythematosus. STAT1-GOF mutations are highly penetrant with a median age at onset of 1 year and often underlie an autosomal dominant trait. As many as 105 mutations at 72 residues, including 65 recurrent mutations, have already been reported in more than 400 patients worldwide. The GOF mechanism involves impaired dephosphorylation of STAT1 in the nucleus. Patient cells show enhanced STAT1-dependent responses to type I and II interferons (IFNs) and IL-27. This impairs Th17 cell development, which accounts for CMC. The pathogenesis of autoimmunity likely involves enhanced type I IFN responses, as in other type I interferonopathies. The pathogenesis of other infections, especially those caused by intramacrophagic bacteria and fungi, which are otherwise seen in patients with diminished type II IFN immunity, has remained mysterious. The cumulative survival rates of patients with and without severe disease (invasive infection, cancer, and/or symptomatic aneurysm) at 60 years of age are 31% and 87%, respectively. Severe autoimmunity also worsens the prognosis. The treatment of patients with STAT1-GOF mutations who suffer from severe infectious and autoimmune manifestations relies on hematopoietic stem cell transplantation and/or oral JAK inhibitors.

Successful Allogenic Stem Cell Transplantation in Patients with Inherited CARD9 Deficiency.

Autosomal recessive (AR) CARD9 (caspase recruitment domain-containing protein 9) deficiency underlies invasive infections by fungi of the ascomycete phylum in previously healthy individuals at almost any age. Although CARD9 is expressed mostly by myeloid cells, the cellular basis of fungal infections in patients with inherited CARD9 deficiency is unclear. Therapy for fungal infections is challenging, with at least 20% premature mortality. We report two unrelated patients from Brazil and Morocco with AR CARD9 deficiency, both successfully treated with hematopoietic stem cell transplantation (HSCT). From childhood onward, the patients had invasive dermatophytic disease, which persisted or recurred despite multiple courses of antifungal treatment. Sanger sequencing identified homozygous missense CARD9 variants at the same residue, c.302G>T (p.R101L) in the Brazilian patient and c.301C>T (p.R101C) in the Moroccan patient. At the ages of 25 and 44 years, respectively, they received a HSCT. The first patient received a HLA-matched HSCT from his CARD9-mutated heterozygous sister. There was 100% donor chimerism at D + 100. The other patient received a T cell-depleted haploidentical HSCT from his CARD9-mutated heterozygous brother. A second HSCT from the same donor was performed due to severe amegakaryocytic thrombocytopenia despite achieving full donor chimerism (100%). At last follow-up, more than 3 years after HSCT, both patients have achieved complete clinical remission and stopped antifungal therapy. HSCT might be a life-saving therapeutic option in patients with AR CARD9 deficiency. This observation strongly suggests that the pathogenesis of fungal infections in these patients is largely due to the disruption of leukocyte-mediated CARD9 immunity.

Inherited CARD9 Deficiency: Invasive Disease Caused by Ascomycete Fungi in Previously Healthy Children and Adults.

Autosomal recessive CARD9 deficiency underlies life-threatening, invasive fungal infections in otherwise healthy individuals normally resistant to other infectious agents. In less than 10 years, 58 patients from 39 kindreds have been reported in 14 countries from four continents. The patients are homozygous (n = 49; 31 kindreds) or compound heterozygous (n = 9; 8 kindreds) for 22 different CARD9 mutations. Six mutations are recurrent, probably due to founder effects. Paradoxically, none of the mutant alleles has been experimentally demonstrated to be loss-of-function. CARD9 is expressed principally in myeloid cells, downstream from C-type lectin receptors that can recognize fungal components. Patients with CARD9 deficiency present impaired cytokine and chemokine production by macrophages, dendritic cells, and peripheral blood mononuclear cells and defective killing of some fungi by neutrophils in vitro. Neutrophil recruitment to sites of infection is impaired in vivo. The proportion of Th17 cells is low in most, but not all, patients tested. Up to 52 patients suffering from invasive fungal diseases (IFD) have been reported, with ages at onset of 3.5 to 52 years. Twenty of these patients also displayed superficial fungal infections. Six patients had only mucocutaneous candidiasis or superficial dermatophytosis at their last follow-up visit, at the age of 19 to 50 years. Remarkably, for 50 of the 52 patients with IFD, a single fungus was involved; only two patients had IFDs due to two different fungi. IFD recurred in 44 of 45 patients who responded to treatment, and a different fungal infection occurred in the remaining patient. Ten patients died from IFD, between the ages of 12 and 39 years, whereas another patient died at the age of 91 years, from an unrelated cause. At the most recent scheduled follow-up visit, 81% of the patients were still alive and aged from 6.5 to 75 years. Strikingly, all the causal fungi belonged to the phylum Ascomycota: commensal Candida and saprophytic Trychophyton, Aspergillus, Phialophora, Exophiala, Corynesprora, Aureobasidium, and Ochroconis. Human CARD9 is essential for protective systemic immunity to a subset of fungi from this phylum but seems to be otherwise redundant. Previously healthy patients with unexplained invasive fungal infection, at any age, should be tested for inherited CARD9 deficiency. KEY POINTS: • Inherited CARD9 deficiency (OMIM #212050) is an AR PID due to mutations that may be present in a homozygous or compound heterozygous state. • CARD9 is expressed principally in myeloid cells and transduces signals downstream from CLR activation by fungal ligands. • Endogenous mutant CARD9 levels differ between alleles (from full-length normal protein to an absence of normal protein). • The functional impacts of CARD9 mutations involve impaired cytokine production in response to fungal ligands, impaired neutrophil killing and/or recruitment to infection sites, and defects of Th17 immunity. • The key clinical manifestations in patients are fungal infections, including CMC, invasive (in the CNS in particular) Candida infections, extensive/deep dermatophytosis, subcutaneous and invasive phaeohyphomycosis, and extrapulmonary aspergillosis. • The clinical penetrance of CARD9 deficiency is complete, but penetrance is incomplete for each of the fungi concerned. • Age at onset is highly heterogeneous, ranging from childhood to adulthood for the same fungal disease. • All patients with unexplained IFD should be tested for CARD9 mutations. Familial screening and genetic counseling should be proposed. • The treatment of patients with CARD9 mutations is empirical and based on antifungal therapies and the surgical removal of fungal masses. Patients with persistent/relapsing Candida infections of the CNS could be considered for adjuvant GM-CSF/G-CSF therapy. The potential value of HSCT for CARD9-deficient patients remains unclear.

Chronic Candidiasis in Children.

PURPOSE OF REVIEW: Healthy children may develop candidal infections as the result of exposure to antibiotics or corticosteroids, but chronic candidiasis in children after the newborn period is unusual. Chronic mucocutaneous candidiasis (CMC) refers to a group of conditions characterized by recurrent or persistent infections with Candida species, particularly Candida albicans. CMC is a phenotype observed in a spectrum of immunologic disorders, some with endocrinologic and autoimmune features. RECENT FINDINGS: CMC can arise secondary to inherited or acquired T cell deficiencies, but in children is largely due to inborn errors impairing the dectin pathway and IL-17 immunity. We review the current understanding of the pathogenesis of chronic mucocutaneous candidiasis and discuss the immunologic pathways by which the immune system handles Candida. We highlight the historical and recent knowledge of CMC in children, emphasizing recent insights into basic science aspects of the dectin pathway, IL-17 signaling, consequences of AIRE gene defects, and clinical aspects of inheritance, and features that distinguish the different syndromes. The clinical phenotype of CMC has many underlying genetic causes. Genetic testing is required for definitive diagnosis.

Th2 and Th9 responses in patients with chronic mucocutaneous candidiasis and hyper-IgE syndrome.

BACKGROUND: STAT1 mutations cause chronic mucocutaneous candidiasis (CMC), while STAT3 mutations cause hyper-IgE syndrome (HIES). CMC and HIES patients have T helper (Th) 17 defects suffering from mucosal Candida infections, but only patients with HIES show an allergic phenotype with eczema, eosinophilia and high IgE levels. OBJECTIVE: We investigated whether differential Th2 and Th9 responses may explain the clinical differences. METHODS: Peripheral blood mononuclear cells of patients with CMC (n = 4), patients with HIES (n = 4), patients with atopic dermatitis (n = 4) and healthy volunteers (n = 13) were stimulated with Candida and Staphylococcus aureus, with and without IL-4. The cytokines IL-5, IL-13, IL-9, IL-17 and TGFß and regulatory T cells were measured in cell culture supernatants by ELISA or flow cytometry, respectively. RESULTS: Peripheral blood mononuclear cells of patients with CMC showed a significantly impaired production of the Th2 cytokines IL-5 and IL-13, especially in the presence of IL-4. Moreover, IL-9 production was significantly lower in patients with CMC compared to healthy controls. In contrast, patients with HIES and patients with AD showed normal IL-5 and IL-13 production, while IL-9 production was significantly lower in patients with HIES compared to healthy controls. Although TGFß was involved in the IL-4-induced IL-9 production, TGFß levels and the frequency of regulatory T cells did not differ between patients with HIES and controls. Flow cytometry analysis demonstrated an IL-9+ IL-17+ CD4+ subset in healthy controls after stimulation with Candida which was less present in patients with HIES. CONCLUSION: Patients with CMC have a general Th defect including Th2 and Th9, while patients with HIES have normal Th2 cytokines. These differences are in line with their clinical presentation. Surprisingly, the allergic cytokine IL-9 was deficient in both HIES and CMC, suggesting a Th-17-derived origin.

Treatment options for chronic mucocutaneous candidiasis.

Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a rare and severe primary immunodeficiency that is characterized by mucocutaneous fungal infection, autoimmunity, cerebral aneurysms, and oropharyngeal and esophageal cancer. Recently, it was discovered that STAT1 mutations are responsible for AD-CMC. These mutations lead to the inability of STAT1 to be dephosphorylated, resulting in hyperphosphorylation, increased binding to the DNA, and gain of function (GOF) effects on STAT1 signaling. Furthermore, a characteristic feature of AD-CMC patients is deficiency in the T-helper 17 (Th17) responses, which is believed to be the immunological cause of the mucocutaneous fungal infection. No targeted treatment other than lifelong antifungal prophylaxis exists for AD-CMC. However, the discovery of the genetic and immunological defects makes it now possible to explore new treatment strategies. This review will discuss immunomodulatory treatment options that can be explored in patients with STAT1 GOF mutations.

Dehydrated human amnion/chorion membrane for the treatment of severe skin and tissue loss in an preterm infant: a case report.

Extreme prematurity complicated with severe congenital cutaneous candidiasis (CCC) is rare and clinically challenging. We present the case of a 615g dizygotic twin delivered at 24 weeks gestation with congenital candidiasis, who developed severe skin and tissue loss, successfully treated with dehydrated human amnion/chorion membrane (dHACM). The infant had a complicated medical course, including treatment for patent ductus arteriosus (PDA), necrotising enterocolitis (NEC), and neonatal abstinence syndrome (NAS). In the operating room after debridement, dHACM was placed over all abdominal and back areas of skin loss and covered with a non-occlusive, non-adherent silver dressing. This dressing regimen was chosen in an effort to provide not only topical antimicrobial coverage, but also to maintain a non-shear, moist wound healing environment, which was so important in the dry incubator environment of the neonatal intensive care centre. Over the next four weeks, the baby was medically managed, and the wounds healed on their own with only weekly bedside dressing changes. This case report provides the first example of successful complex management of extensive life-threatening wounds in a premature infant using dHACM.

IL-17 and infections

IL-17 immunity has been shown to be essential for mucocutaneous protection against Candida albicans in mice and humans. However, mice with defective IL-17 immunity display broader susceptibility, as they are also prone to infections with diverse infectious agents at various sites. Humans with genetic defects affecting their IL-17 immunity usually suffer from chronic mucocutaneous candidiasis (CMC): recurrent or persistent infections of the skin, nails, and mucosae with C. albicans, with or without other clinical signs. Most patients with autosomal dominant (AD) hyper-IgE syndrome (HIES) due to STAT3 deficiency or AD STAT1 gain-of-function display impaired IL-17-producing T-cell development, and CMC is one of their principal clinical manifestations. Similarly, patients with autosomal recessive (AR) autoimmune polyendocrine syndrome type 1 (APS-1) caused by AIRE deficiency have high levels of neutralizing autoantibodies against IL-17A, IL-17F and/or IL-22 and present CMC as their only infectious disease. Finally, CMC is the main clinical phenotype observed in patients with inborn errors specifically affecting IL-17 immunity. Indeed, patients with AD IL-17F deficiency or AR IL-17RA or ACT1 deficiency display CMC and, to a lesser extent, superficial staphylococcal diseases. Candida infection was recently reported in psoriasis patients treated with anti-IL-17A antibodies. Careful monitoring for CMC is thus important during anti-IL-17 treatment

Se ha demostrado que la inmunidad IL-17 es esencial para la protección mucocutánea contra la Candida albicans en ratones y humanos. Independientemente, los ratones con inmunidad IL-17 defectuosa muestran una susceptibilidad más amplia, de modo que también son propensos a infecciones por diversos agentes infecciosos en varios lugares. Los humanos con defectos genéticos que afectan su inmunidad IL-17 habitualmente padecen candidiasis mucocutánea crónica (CMC): infecciones cutáneas recurrentes o persistentes de uñas y mucosas por C. albicans, con o sin otros signos clínicos. Muchos pacientes con síndrome de hiper IgE autosómico dominante (AD-HIES) debido a deficiencia STAT3 o a aumento de función AD STAT1 muestran un desarrollo dañado de células T productoras de IL-17 y la CMC es una de sus principales manifestaciones. De igual manera, los pacientes con síndrome poliendocrino autoinmune tipo 1 recesivo autosómico (AR-APS-1) causado por deficiencia de AIRE (regulador autoinmune) presentan altos niveles de anticuerpos neutralizantes contra IL-17A, IL-17F y/o IL-22 y padecen CMC como su única enfermedad infecciosa. Finalmente, la CMC es el principal fenotipo clínico observado en pacientes con errores innatos, específicamente aquellos que afectan la inmunidad IL-17. De hecho, los pacientes con deficiencia AD IL-17F o deficiencia IL-17RA o ACT1 presentan CMC y, en menor medida, enfermedades estafilocócicas superficiales. Se ha informado recientemente CMC en pacientes tratados con anticuerpos anti-IL-17A. Es importante el control cuidadoso de la CMC en estos pacientes durante el tratamiento con anti-IL-17ª

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy and other primary immunodeficiency diseases help to resolve the nature of protective immunity against chronic mucocutaneous candidiasis.

PURPOSE OF REVIEW: This review summarizes and discusses the most recent and important publications describing Mendelian diseases associated with susceptibility to chronic mucocutaneous candidiasis (CMC) as a means of gaining insight into the pathogenesis of this immunodeficiency. RECENT FINDINGS: Impairment to T helper 17 (Th17) cell-associated signalling pathways are common in immunodeficiency syndromes associated with CMC infections. Mutations in CARD9, STAT3, IL17RA, IL17F, STAT1, and IL12RB and polymorphisms in Dectin 1 and interleukin-22 (IL-22) encoding genes have been shown to impair the development or function of Th17 cells and are associated with susceptibility to candidiasis. Studies on autoimmune polyendocrinopathy candidiasis ectodermal dystrophy have revealed autoimmunity to Th17 cytokines and cells as the basis for CMC. IL-17A, IL-17F, and IL-22 induce production of antimicrobial peptides and chemoattractants that recruit neutrophils in response to invading fungi. Th17 cell-associated cytokines may play a role in shaping the host's microbiome (that competes with C. albicans) preventing overgrowth of this pathogen. Recent evidence also suggests that IL-22 together with IL-17F might be the most important Th17 cytokine in protection against Candida. SUMMARY: Dissection of critical molecular and immunological mechanisms will allow the development of new treatments for primary and secondary immunodeficiency disorders resulting in chronic Candida infections.

Avalia ao da susceptibilidade a antifungicos de diferentes espécies de leveduras candida isoladas de mucosa bucal e pele / Evaluation of antifungal susceptibility of different species of candida yeast isolated from buccal mucosa and skin

A variabilidade das diferentes especies de Candida sp, juntamente com as distintas respostas as formas de tratamento, desenvolveram a necessidade da utiliza tao de diferentes metodos diagn6sticos e esquemas terapeuticos. Entre as leveduras deste grupo, a Candida albicans e urn dos pat6genos mais comuns envolvidos nas candidiases mucocutaneas e da orofaringe, porem as especies nao albicans tern aumentado em numero e em importancia devido ao acrescimo do perfil de resistencia aos antifUngicos. A resistencia da Candida albicans e das especies nao albicans ao fluconazole outros derivados az61icos e descrito na literatura com freqOencia, o que torna importante a realiza tao de testes de susceptibilidade. Neste contexte esta pesquisa tern como objetivo determinar o perfil de susceptibilidade das leveduras Candida em diferentes sftios anatomicos. As leveduras isoladas da mucosa bucal e de pele foram semeadas em CHROMagar Candida, incubadas por 48 horas, a 35°C sendo posteriormente identificadas e avaliado in vitro o perfil de susceptibilidade utilizando o metodo da macrodilui tao. Entre as 25 amostras analisadas, verificou-se urn perfil de resistencia maior ao fluconazol em compara tao ao cetoconazol, sendo que 44% dos isolados de boca e 50% de pele mostraram-se resistentes ao fluconazol.

The variability of the different species of Candida sp, together with the distinct responses to treatment, elicited the need of using different diagnostic methods and therapeutic programs. Among the yeast of this group, Candida albicans is one of the most common pathogens involved in muco-cutaneous and oropharingeal candidiases, but the non-albicans species have increased in number and importance due to antifungal resistance. The resistance of Candida albicans and the non-albicans species to fluconazole and other azolic derivatives is frequently reported, which makes susceptibility tests important. Within this scope, this research has the purpose of determining the susceptibility profile of Candida yeast from different anatomical sites. The yeast cells isolated from buccal mucosa and skin were seeded in CHROMagar Candida, incubated for 48 hours at 35°C; later, they were identified and the susceptibility profile was assessed in vitro using themacrodilution method. Of the 25 samples analyzed, a higher profile of resistance to fluconazole compared to ketoconazole was noticed, where 44% ofthe buccal and 50% ofthe skin isolates were resistant to fluconazole.

Candidiasis mucocutánea crónica. Informe de un caso / Chronic mucocutaneous candidiasis. Case report

La candidiasis mucocutánea crónica (CMC) es una inmunodeficienciaprimaria que se caracteriza por infecciones candidiásicaspersistentes o recurrentes en piel, uñas o membranas mucosas. La CMC puede asociarse con endocrinopatías, comohipoparatiroidismo, enfermedad de Addison, hipotiroidismo, diabetes mellitus de tipo 1 o hipogonadismo; otras patologías asociadas son enfermedades autoinmunitarias, como gastritis autoinmunitarias y hepatitis autoinmunitaria. Se presentauna paciente con CMC con déficit específico de linfocitos T ycélulas NK, sin otra enfermedad asociada.

Candidiasis mucocutánea crónica. Informe de un caso / Chronic mucocutaneous candidiasis. Case report

La candidiasis mucocutánea crónica (CMC) es una inmunodeficienciaprimaria que se caracteriza por infecciones candidiásicaspersistentes o recurrentes en piel, uñas o membranas mucosas. La CMC puede asociarse con endocrinopatías, comohipoparatiroidismo, enfermedad de Addison, hipotiroidismo, diabetes mellitus de tipo 1 o hipogonadismo; otras patologías asociadas son enfermedades autoinmunitarias, como gastritis autoinmunitarias y hepatitis autoinmunitaria. Se presentauna paciente con CMC con déficit específico de linfocitos T ycélulas NK, sin otra enfermedad asociada.(AU)

Chronic mucocutaneous candidiasis and oesophageal cancer.

Chronic mucocutaneous candidiasis (CMC) is often accompanied by endocrine or inflammatory disorders. The association of CMC with squamous cell carcinoma of the oral cavity or oesophagus have been described in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). We describe three cases of CMC and oesophageal cancer without the APECED syndrome. The first case refers to a 41-year-old man with Candida paronychia and oral infection and selective IgA deficiency since childhood, who later developed an oesophageal cancer. The second case is a 30-year-old man who presented CMC features at the age of 2 together with selective IgA deficiency. Later on he was diagnosed with an oesophageal squamous cell carcinoma. His mother, the third case reported, had oral thrush since childhood and at the age of 29 she presented with an oesophageal squamous cell carcinoma. The three patients reported died due to oesophageal cancer. This is the first case report describing the development of oesophageal cancer in patients with CMC without the APECED syndrome. Patients with CMC need close follow-up with good oral hygiene and aggressive treatment of oral and oesophageal candidiasis. Routine endoscopic screening for patients with CMC that develop symptoms of oesophageal candidiasis and for patients with CMC with a family history of oesophageal cancer is suggested. Avoidance of additional risk factors for oral and oesophageal cancer like cigarette smoking and excessive alcohol consumption are also warranted.