| APECED (autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy)Essentials - Suspect the disease in all children and young adults with one or more of the following, otherwise unexplained symtoms or conditions:
- persistent or recurrent oral candidiasis [1]; may also occur in the oesophagus, on the skin and in the nails
- in mild cases rhagades of the corners of mouth [2]
- hypoparathyroidism or Addison's disease
- alopecia
- chronic keratoconjunctivitis
- autoimmune hepatitis of a child
- flashing erythema with fever; may be associated with arthralgia
- chronic diarrhoea or severe obstipation.
- The suspicion is strengthened by presence of
- enamel hypoplasia of permanent teeth [3]
- pitted nail dystrophy [4].
 Epidemiology - Around 400 cases have been diagnosed worlwide.
- Autosomal recessive inheritance: mutations of both AIRE genes (chromosome 21q22.3)
- Occurs in all populations; so far most frequently recognized in people of Finnish, Sardinian and Iranian Jewish origin
- The clinical picture and course are highly variable causing delay in the diagnosis, or the diagnosis may be missed.
Clinical picture - The clinical picture and course of the disease are highly variable. The number of the different disease components may vary from two to over ten. Most frequently the first symptoms are sore mouth corners, often together with candidal coatings of the mucosal membranes of the mouth, symptoms of hypocalcaemia (clumsiness, vague tetany, convulsions, often in connection to febrile infection), or weakness, fatigue and weight loss.
- However, instead of candidiasis, hypoparathyroidism and Addison’s disease, the early clinical picture may be predominated by any other disease component, e.g. keratoconjunctivitis, flashing erythema with fever, or hepatitis (see table [1]).
- The first components usually appear before the age of 15 years, but sometimes only in adulthood. New components may develop throughout life.
Table 1. Prevalence (%) of disease components of APECED at ages 10 and 40 years in Finnish series of 91 patients | Component | at 10 years | at 40 years | | Candidiasis in the mouth and/or on the skin | 83 | 100 | | At least one endocrinopathy | 74 | 100 | | Hypoparathyroidism | 65 | 87 | | Addison’s disease | 40 | 81 | | Diabetes mellitus | 3 | 23 | | Hypothyroidism | 1 | 21 | | Ovarian atrophy | – | 69 | | Male hypogonadism | – | 28 | | Keratoconjunctivitis | 18 | 22 | | Pernicious anaemia | 3 | 28 | | Hepatitis, active or inactive | 12 | 18 | | Chronic diarrhoea | 13 | 22 | | Severe obstipation | 10 | 26 | | Lack of spleen | 9 | ≥ 19 | | Tubulointerstitial nephritis | 2 | ≥ 7 | | History of flashing erythema with fever | 12 | 14 | | History of ocular choroiditis | ≥ 2 | ≥ 8 | | Alopecia (loss of hair) | 16 | 39 | | Vitiligo | 9 | 31 |
Basic disorder - In the lack of a functioning AIRE gene, the elimination of autoreactive T-lymphocytes in the thymus does not take place normally; the patient is predisposed to autoimmune destruction of a number of organs. Associated with this, the patient is unable to fend off superficial candida infections.
Important investigations - Genetic diagnosis is available for most patients and carriers. Determination of autoantibodies may reveal an on-going destruction of the adrenal cortex, ovaria and parietal cells of the stomach. Antibodies associated with type 1 diabetes and autoimmune thyroiditis are common, but their predictive value is weaker, i.e. they are more common than actual diabetes or hypothyroidism. Laboratory investigations are important in discovering new hormone deficiencies and in the follow-up of hormone treatment.
Treatment and follow-up - An endocrinologist should be consulted in suspected cases, and must supervise the management of the patients aside from the family doctor.
- The possible development of new disease components should be monitored with regular laboratory investigations. In principle, each disease component is treated as if it were an independent disease. The endocrine components and their treatment will, however, affect each other.
- Oral and oesophageal candidiasis must be effectively controlled, because it is carcinogenic. Oral ulceration that does not heal within a week warrants biopsy. Follow-up by a specialist of oral medicine is recommended.
Disease burden - The burden varies depending on the clinical picture. A shared burden for all the patients is the awareness that at any time they may develop new, possibly life-threatening (mucosal carcinoma, hepatitis) components of the disease.
- Endocrinological disturbances, especially hypoparathyroidism, Addison’s disease and diabetes, particularly when they occur in the same patient, require in addition to daily medication strict follow-up and may restrict functional ability.
- Cosmetic problems (alopecia, vitiligo, abnormalities of the mouth and teeth) may be psychologically demanding.
- Life expectancy is normal for the majority of the patients, if the quality of follow-up and treatment is good and the patient together with the family learns to take responsibility for it. This may be very problematic especially in the adolescence.
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