Severe COVID-19 illness in an Indian adolescent with autoimmune polyendocrinopathy syndrome-1

Autoimmune polyglandular syndrome-1 (APS-1)also known as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy is a rare autosomal recessive disorder caused by mutation of AIRE gene on chromosome 21q22.3 with an overall prevalence of <1:100,000. Here, we present a 16-year-old male having clinical history of evolution of symptoms for oral candidiasis, hypoparathyroidism, and adrenal insufficiency (AI). He developed rare endocrine and non-endocrine manifestations such as type-1 diabetes (T1D) and autoimmune hepatitis, respectively. The patient while on hormone replacement therapy along with immunosuppressants developed liver cirrhosis and portal hypertension with esophageal varices and candidiasis. Subsequently, he was admitted for complaints of cough, cold and fever and was confirmed to be affected by SARS-CoV-2 by reverse transcription-polymerase chain reaction method. In his prolonged ICU stay of 26 days, he required oxygen therapy, intravenous glucocorticoids, remdesivir, low molecular weight heparin, and hemodynamic support with inotropes. His medical management with subcutaneous insulin therapy and azathioprine was continued. He was discharged after complete resolution of symptoms and negative tests for SARS-CoV-2 and was advised radiological and clinical follow-up. Reports suggest that risk of severe COVID does not increase in patients with AI or autoimmunity. However, our patient possibly developed severe COVID not only due to AI and autoimmunity but also associated rare manifestations like hyperglycemia due to T1D and cirrhosis. Thus, good glycemic control and well-tolerated modern immunosuppressant therapy may be useful in improving prognosis of severe COVID-19 illness in patients with APS-1.

Autoimmune Polyglandular Syndrome Type II presenting as Subacute Combined Degeneration of Spinal Cord: A Neuroendocrinology Crossroad

Introduction - Autoimmune polyglandular syndrome (APS) is a condition having multiple endocrine abnormalities. It is divided into three types depending on the involvement of various endocrinopathies. It is also associated with other systemic involvement. The basic pathophysiology of this syndrome revolves around autoimmunity. Case Presentation - We present a 50 year old gentleman who presented to us in emergency with subacute onset progressive weakness of both lower limbs followed by upper limbs. On examination, patient was confused and disoriented. General examination findings include hypotension, pallor, facial puffiness and vitiligo. Neurological examination revealed spasticity and motor weakness in all four limbs with extensor planter response. Sensory examination during hospital course revealed posterior column involvement. Laboratory and radiological investigations confirmed subacute combined degeneration of spinal cord secondary to pernicious anaemia, Addison’s disease and autoimmune thyroid disease. The final diagnosis of autoimmune polyglandular syndrome type II was made after fulfilment of the required criteria. Conclusion – Autoimmune polyglandular syndrome type II can rarely present to neurologist as subacute combined degeneration of spinal cord. This syndrome and its systemic association should be kept in mind in order to reach the final diagnosis.

Attenuation of Autoimmune Phenomena in a Patient with Autoimmune Polyglandular Syndrome Type 1

Autoimmune polyglandular syndrome type 1 (APS1) is a progressive life-threatening illness with no known cure. Current treatments involve replacement of the hormone deficiencies that result from autoimmune destruction of multiple endocrine organs. We report on a girl whose disease was progressing rapidly until she began on immunosuppressive agents. A healthy 6-year-old girl with no remarkable medical history presented with new onset hypocalcemic seizures and primary hypoparathyroidism. Howell-Jolly bodies consistent with autoimmune hyposplenism were also noted. Genetic testing revealed compound heterozygosity for 2 disease-associated variants in the autoimmune regulator (AIRE) gene. She later developed elevated liver enzymes, primary adrenal insufficiency, and alopecia totalis. Serologic testing revealed antibodies to 21-hydroxylase, intrinsic factor, and smooth muscle. Hydrocortisone was initiated for adrenal insufficiency. Shortly afterwards, her liver enzymes normalized, and her smooth muscle antibody levels began to decline. Serologic testing performed at age 11 revealed seropositivity for glutamic acid decarboxylase (GAD) antibodies, antinuclear antibodies, and Sjögren syndrome A (SSA) antibodies. At age 12, she was given 2 doses of rituximab. Hair loss rapidly progressed to alopecia totalis and then to alopecia universalis, at which time oral methotrexate treatment was initiated. For the past 7 years while on glucocorticoid and methotrexate treatment, our patient has displayed normalization of 2 antibodies, a lack of progression to additional autoimmune diseases, and experienced reversal of alopecia universalis.

Autoimmune polyglandular syndrome type I. Features of clinical manifestations, difficulties in diagnosis and methods of correction

Autoimmune polyglandular syndrome (APG) type I is an orphan disease with autosomal recessive inheritance caused by mutations in the autoimmune regulator gene (AIRE); the disease onset typically occurs in childhood. The disease is characterized by a wide variety of clinical manifestations with a certain stage in the manifestation of individual symptoms. The rare occurrence of this pathology determines its late diagnosis, which can lead to the decompensated life-threatening conditions and an unfavorable outcome. Widely informing pediatric specialists will contribute to the development of a diagnostic algorithm for timely verifying the disease from the moment its first clinical manifestations appear, and will improve the quality and life expectancy of the patients.

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type-1 (APS-1), is a rare monogenic autoimmune disease caused by loss-of-function mutations in the autoimmune regulator (AIRE) gene. AIRE deficiency impairs immune tolerance in the thymus and results in the peripheral escape of self-reactive T lymphocytes and the generation of several cytokine- and tissue antigen-targeted autoantibodies. APECED features a classic triad of characteristic clinical manifestations consisting of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and primary adrenal insufficiency (Addison's disease). In addition, APECED patients develop several non-endocrine autoimmune manifestations with variable frequencies, whose recognition by pediatricians should facilitate an earlier diagnosis and allow for the prompt implementation of targeted screening, preventive, and therapeutic strategies. This review summarizes our current understanding of the genetic, immunological, clinical, diagnostic, and treatment features of APECED.

Late Presentation of Neglected Autoimmune Polyglandular Syndrome

A 60-year-old male patient, weighing 40 kg, having a BMI of 13, who was also a known case of Diabetes Mellitus Type II was shifted to the Orthopaedic Ward last month due to a fall, which led him to develop an intertrochanteric fracture in the femur. While the treatment of the patient was in an ongoing status for his fracture, his Diabetes was seen to be poorly controlled, with his blood glucose levels being constantly evaluated to be in a state of severe hypoglycaemia to slightly increased levels of blood glucose. On examination, the patient showed clear signs of being malnourished. He was in a bad and dishevelled state, he had creases on the palmar aspects of his hands and hyperpigmentation on his buccal mucosa. Furthermore, his lab reports revealed abnormalities in nearly every lab test ordered. Not only did he have elevated ACTH levels, but there was also a failure of Cortisol stimulation. His DEXA Scan showed that he was predisposed to develop severe osteoporosis and his malnourished condition was supportive of promoting that condition even more. The patient was diagnosed to be suffering from Autoimmune Polyglandular Syndrome, Type II. This is a rare condition of one of its kind where there is a pre-existence of autoimmune adrenal insufficiency along with either autoimmune thyroid disease or autoimmune diabetes mellitus. Since this condition is rare, it tends to often get overlooked upon diagnosis, leading to misdiagnosis because almost all of the presenting features or the symptoms of the prevalent endocrinological disorders present in this condition mimic either hypothyroidism, or diabetes, or adrenal insufficiency alone, and thus lead to further consequences when the condition does not resolve despite persistent treatment, such as the case in this patient. This paper reviews the background of the patient and the causes that possibly could have made him reach this advanced stage of the disease. The paper also reflects upon the disease, Autoimmune Polyglandular Syndrome Type II, as a whole and elaborates on the symptoms and signs which the patient tens to confuse with other endocrinological diseases. Lastly, this paper shall also review the appropriate management plan for the patient to ease his symptoms and accelerate his recovery process.