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Year : 2018  |  Volume : 19  |  Issue : 3  |  Page : 241-244

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

1 Department of Pediatric Medicine, Institute of Child Health, Kolkata, West Bengal, India
2 Department of Pediatric Dermatology, Institute of Child Health, Kolkata, West Bengal, India

Date of Web Publication28-Jun-2018

Correspondence Address:
Dr. Aniruddha Ghosh
Department of Pediatric Medicine, Institute of Child Health, Kolkata, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.IJPD_20_17

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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.

Keywords: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, Candida, chronic mucocutaneous candidiasis, hyper IgE syndrome, immunologic deficiency syndromes, Job's syndrome

How to cite this article:
Mahto B, Kundu P, Ghosh A, Dhar S. A novel case of chronic mucocutaneous candidiasis: Overlap between autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy syndrome and hyper IgE syndrome. Indian J Paediatr Dermatol 2018;19:241-4

How to cite this URL:
Mahto B, Kundu P, Ghosh A, Dhar S. A novel case of chronic mucocutaneous candidiasis: Overlap between autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy syndrome and hyper IgE syndrome. Indian J Paediatr Dermatol [serial online] 2018 [cited 2021 Dec 4];19:241-4. Available from: https://www.ijpd.in/text.asp?2018/19/3/241/211809

  Introduction Top

Chronic mucocutaneous candidiasis (CMC) is a rare heterogenous group of disorders in which affected individual with underlying congenital, endocrinal, or immunological abnormalities develops recurrent or persistent and progressive infections of mucosa, skin, and its appendages (hair, nail) with Candida sp., sometimes refractory to antifungal therapy. Early-onset (infancy) CMC is more common (60%–80%) whereas late-onset disease is rare, occurring as late as in the second decade of life.[1],[2] Cases of CMC in association with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome, hyper IgE syndrome, or other immunodeficiencies have been reported;[3],[4] however, no case of CMC with overlapping APECED and hyper IgE syndrome has been reported so far to the best of our knowledge.

  Case Report Top

A 14-year-old male patient, the second child born out of non-consanguineous marriage, presented with failure to thrive and multiple crusted and hyperpigmented nodular lesion involving scalp, face, and ears. There was no history of fever, cough, or shortness of breath, but the child had decreased appetite for the last 1 week. The child had a history of repeated hospitalization since 1 month of age with similar complaints. There was also a history of recurrent bilateral “red eyes with watering” and multiple cold abscesses involving face, chest, and upper part of back which healed with scarring. He had an uneventful perinatal history. There was no history of similar illness among the family members.

On examination, child had asymmetrical face with frontal prominence, deep-seated wide spaced eyes, and fleshy nose tip with some nodular growth and coarse skin [Figure 1]. There were pallor, few palpable cervical lymph nodes, and grade 3 clubbing of all the fingers of both upper and lower limbs with dystrophy of a few [Figure 2]. There was also a thick-crusted horn-like lesion over scalp with scarring alopecia [Figure 3] which bled with any attempt to remove it. Similar crusted lesions were also noticed over the ears [Figure 4], nose, and perianal regions. The child had multiple scars of healed lesions over face, chest, and upper part of back [Figure 5]. There were adherent curd-like whitish plaques involving tongue, palate, and pharyngeal wall suggestive of oropharyngeal candidiasis, and the presence of two deciduous teeth was also noted. The child had bilateral interstitial keratitis, result of recurrent corneal ulceration with leukoma of the left eye [Figure 6]. Otoscopic examination revealed perforation of the left tympanic membrane with no purulent/mucoid discharge. Mild hepatomegaly was noted on abdominal examination. On anthropometry, both height and weight were below third percentile for the age. Immunization was incomplete due to repeated hospitalization.
Figure 1: Showing typical facies with frontal prominence, deep-seated wide-spaced eyes (note bilateral corneal haziness), and fleshy nose tip with some nodular growth and coarse skin

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Figure 2: Showing grade 3 clubbing of fingers of left hand, also note the fungal periungual infiltration along with dystrophy of nail in one finger

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Figure 3: Thick-crusted horn-like lesions over scalp with scarring alopecia

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Figure 4: Showing hyperkeratotic nodular scaly lesions due to cutaneous infiltration of Candida sp.

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Figure 5: Dystrophic skin over the whole back of the trunk along with scar marks produced due to recurrent abscesses (”cold abscess”) involving skin

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Figure 6: Left eye showing haziness due to interstitial keratitis with leukoma, a result of recurrent keratitis

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Laboratory investigations were suggestive of iron deficiency anemia (hemoglobin - 7 g/dl, platelet - 9.1 lac/cmm, mean corpuscular volume - 71 fl, mean corpuscular hemoglobin - 19.9 pg, mean corpuscular hemoglobin concentration - 27.8 g/dl, ferritin - 20 μg/dl, serum unsaturated iron-binding capacity - 450 μg/dl). HIV serology and workup for tuberculosis (Mantoux tests, chest radiograph, sputum for AFB and GeneXpert) were negative. Although complement level and T-lymphocyte counts (total count - 1694 cells/μl, CD4 – 898, and CD8-736 cells/μl with CD4/CD8 ratio of 1.22) were within normal range (C3-118 mg/dl, C4-17.1 mg/dl), he had high level of serum IgE (1404 IU/ml) with other immunoglobulins within normal ranges. He did not have eosinophilia though Candida sp.was isolated from oropharyngeal swabs. High-resolution computed tomography of the lung did not revealed any sign of bronchiectasis or pneumatocele. No endocrinal abnormality (fasting and postprandial sugar, thyroid and parathyroid profile, serum cortisol level, and serum electrolytes were within normal limits) was noted on evaluation. Unfortunately, genetic study could not be done due to economic reasons.

The child was treated with a combination of fluconazole and itraconazole. Protein and calorie rich diet with vitamins and micronutrients supplementation was given. Corneal ulcer was treated with mega dose of Vitamin A as well antibiotic eye drop. Oral co-trimoxazole was also added considering a case of immunodeficiency though sepsis screen came out to be negative. Appetite and general condition of the child improved after 10 days of treatment and he was discharged with an advice of regular follow-up.

  Discussion Top

CMC is a heterogenous disorder which can begin in the 1st month or as late as two-decade of life.[1] Clinical manifestations and severity of CMC can be varied. Characteristic lesions are whitish plaques with crusts and ulcer which may progress to chronic hyperplastic and nodular lesions. These features may be followed by extensive scaling of skin lesions and exophytic growths as well as thickened nails and swollen periungual tissues.[2] Scalp may be involved with hyperkeratotic granulomatous plaque which can result in scarring alopecia.[3] Nails become thick, dystrophic, and brittle with associated paronychia. Despite severe cutaneous involvement, the patient rarely develops invasive candidiasis.[1] Some patients may have altered iron metabolism leading to iron deficiency or pernicious anemia.[5] Most of the patients have defect in acquired cell-mediated immunity while innate immunity is preserved.

CMC may be associated with underlying conditions such as endocrinopathies, HIV infection, APECED syndrome, DiGeorge syndrome, CARD9 mutation, both type of hyper IgE syndrome, deficiency of IL-17 receptor A, STAT1 and IL-17E, and autoimmune disorders of familial origin.[1]

Autoimmune polyendocrinopathy syndrome type 1, also known as APECED syndrome, a genetic autoimmune disease with onset in infancy combines CMC and several endocrinopathies.[6] The lesions are followed by onset of hypoparathyroidism, hypothyroidism, hypoadrenalism, chronic active hepatitis, pernicious anemia, enamel hypoplasia, type-1 diabetes.[7]

Laboratory evaluation of our patient did not demonstrate any endocrine dysfunction. The patient must be evaluated at the time of diagnosis and later for the development of endocrinopathies as CMC usually precedes endocrine manifestations by several years. Features of endocrinopathies may develop as late as fifth decades of life.[7]

Hyper IgE syndrome, also known as Job's syndrome, is a rare primary immunodeficiency disorder characterized by recurrent cutaneous and pulmonary infections, eczematous dermatitis, and elevated serum IgE level. Two forms – autosomal dominant and autosomal recessive – are recognized, but most of the cases are sporadic.[8],[9]

Hyper IgE syndrome usually presents very early in life. Neonatal pustular and eczematous rashes are usually the first manifestations of the disease typically affecting the face and scalp with eosinophilia. Staphylococcus aureus infection as cold abscess is common.[10]

The characteristic features of autosomal dominant variant of hyper IgE are recurrent staphylococcal cold abscesses, pneumatocoele, skeletal abnormalities, and unusual facies. They often have history of sinusitis and mastoiditis. Facial asymmetry, prominent forehead, deep-set wide-spaced eyes, broad nasal bridge, wide fleshy nasal tip, mild prognathism, and rough appearance of facial skin may be present. Persistence of deciduous teeth due to delayed shedding, scoliosis, and recurrent fracture occurs. These patients show high level of serum IgE with normal concentration of other immunoglobulins. However, IgE level may fluctuate and even decrease in adults.[1] Although IgE level usually exceeds 2000 IU per ml, a normal IgE level should not exclude the presence of the hyper IgE syndrome in an adult or adolescent. A case series demonstrated substantial fluctuations in serum IgE levels over time.[11]

The diagnosis of CMC consists of observation of persistent and recurrent lesions demonstrably caused by Candida sp. Laboratory investigations to exclude endocrinopathies and immunodeficiencies are cornerstones of diagnosis. Our patient had severe recurrent candidal infections with dystrophy of nail and scarring alopecia. Many features suggestive of autosomal dominant hyper IgE syndrome such as facial dysmorphism, multiple scars following recurrent dermal cold abscesses, and persistent deciduous teeth with moderately higher level of serum IgE were demonstrated. Alongside with this, the patient had CMC with ectodermal dystrophy typically seen in early phase of APECED syndrome.

The treatment for CMC consists of therapy for active infections, endocrinopathies, and specific treatment for immunological deficiency if available. Antifungal therapies used are fluconazole and an additional newer azole (in our case, due to low cost and good availability, oral itraconazole was preferred).[1] Nutritional assessment and timely intervention are also very crucial.

  Conclusion Top

Although advanced laboratory investigations are not widely available in India, thorough clinical examination and some baseline tests can provide several important pointers toward a specific underlying etiology. While dealing with a case of CMC, a pediatrician or a dermatologist should always remember to exclude underlying endocrinal abnormalities as well as cellular and humoral immunodeficiency disorders.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


We sincerely thank Dr. Apurba Ghosh, Dr. Priyankar Pal, Dr. Maya Mukhopadhyay, Dr. Arunaloke Bhattacharya, Dr. Jaydeep Choudhury, Dr. Kheya Ghosh Uttam, and Dr. Partha Pratim Halder for their help and support to manage the case.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Buckley RH. Primary combined antibody and cellular immunodeficiencies. In: Kliegman RM, Stanton BF, St. Geme JW 3rd, Schor NF, editors. Nelson Textbook of Pediatrics. 20th ed. Philadelphia: Elsevier; 2016. p. 1028-9.  Back to cited text no. 1
Jorizzo JL. Chronic mucocutaneous candidosis. An update. Arch Dermatol 1982;118:963-5.  Back to cited text no. 2
Kalfa VC, Roberts RL, Stiehm ER. The syndrome of chronic mucocutaneous candidiasis with selective antibody deficiency. Ann Allergy Asthma Immunol 2003;90:259-64.  Back to cited text no. 3
Böni R, Trüeb RM, Wüthrich B. Alopecia areata in a patient with candidiasis-endocrinopathy syndrome: Unsuccessful treatment trial with diphenylcyclopropenone. Dermatology 1995;191:68-71.  Back to cited text no. 4
Masi M, De Vinci C, Baricordi OR. Transfer factor in chronic mucocutaneous candidiasis. Biotherapy 1996;9:97-103.  Back to cited text no. 5
Collins SM, Dominguez M, Ilmarinen T, Costigan C, Irvine AD. Dermatological manifestations of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. Br J Dermatol 2006;154:1088-93.  Back to cited text no. 6
Sonal C, Michael M, Daniele T, Paolo R. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Aesthet Dermatol 2012;5:18-22.  Back to cited text no. 7
Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 2007;448:1058-62.  Back to cited text no. 8
Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, et al. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 2007;357:1608-19.  Back to cited text no. 9
Davis SD, Schaller J, Wedgwood RJ. Job's syndrome. Recurrent, “cold”, staphylococcal abscesses. Lancet 1966;1:1013-5.  Back to cited text no. 10
Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, et al. Hyper-IgE syndrome with recurrent infections – An autosomal dominant multisystem disorder. N Engl J Med 1999;340:692-702.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

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