N eutropenia is a blood disorder characterized by presence of an abnormally low number of neutrophils.
Neutrophils are white blood cells (leukocytes) that serves as the primary defense against infections by destroying bacteria in the blood.
Specfically, neutrophils are a type of granulocyte that contain granules filled with potentchemicals to break down the microbes they ingest. Some of these chemicals, such as histamine, also contribute to inflammation and allergy.
The process of eating and digesting microbes is called phagocytosis. Neutrophils are phagocytes.1
Q: How do neutrophils eat microbes?
A: Segmented neutrophils are the mature phagocytes that migrate through tissues to destroy microbes and respond to inflammatory stimuli. Segmented neutrophils comprise 40-75 % of the peripheral leukocytes. They are usually 9 to 16 µm in diameter. The nuclear lobes, normally numbering from 2 to 5, may be spread out so that the connecting filaments are clearly visible, or the lobes may overlap or twist. The chromatin pattern is coarse and clumped. The cytoplasm is abundant with a few nonspecific granules and a full complement of rose-violet specific granules.1
What Is Neutropenia In Celiac Disease and/or Gluten Sensitivity?
This 21 year-old woman (right) appears as old as her 70 year-old grandmother (left). Courtesy Prof Dr Chua Chung Nen
What Is Acquired Cutis Laxa?
A cquired cutis laxa is an uncommon skin disorder characterized by abnormal reduction and degeneration of elastic fibers of the skin that can appear simply as thick, saggy skin with loose folds to severe involvement showing a premature aged appearance.
Q: What are elastic fibers of the skin?
A: Elastic fibers of the skin are connective tissue found in the dermis, which is the layer of skin under the epidermis, or surface layer. They hold the shape of skin and are important for wound healing in the development of scars.
What Is Cutis Laxa In Celiac Disease and/or Gluten Sensitivity?
Endocrine glands targeted in polyglandular autoimmune syndrome.
What Are Autoimmune Polyglandular Syndromes?
A utoimmune polyglandular syndromes (APS) are rare clusterings of two or more endocrine and non-endocrine autoimmune disorders in the same affected person.
Polyglandular is somewhat of a misnomer since many of the manifestations of the diseases do not concern endocrine glands.1
Endocrine autoimmune disorders involve the abnormal production of autoantibodies that target and destroy the body’s own endocrine tissues, causing loss of essential hormone production by the targeted glands. Endocrine glands include the pituitary, thyroid, adrenal, parathyroid, islets of Langerhans (pancreas), testes in males, and ovaries in females.
First degree relatives (siblings of same parents, parents, children) have an increased incidence of latent, meaning not apparent, autoimmune pathology.2
Q: How many autoimmune polyglandular syndromes are described?
A:Three syndromes have been identified and they are all inherited: APS type-1, APS type-2, and APS type-3.
APS type-1 is a genetic mutation inherited in an autosomal recessive manner. A child with APS type-1 has inherited two mutated copies of a gene called the AIRE (autoimmune regulator) gene, which is on the long arm of 21st chromosome present in each cell.3 The parents, called carriers, are unaffected since they each have only a single copy of the AIRE mutated gene. Humans have a total of 23 pairs of chromosomes that contain genes inherited from each parent. Mutations in the genes cause disease.
Diagnosis criteria for autoimmune polyglandularsyndrome type-1 includes these three disorders:
Chronic candida infection (CMC), which usually develops first, typically attacks skin, but very commonly also nails, mouth, vagina, esophagus and intestine. CMC in APS type-1 patients is usually mild, and in most cases, it is chronic. It is found in 73–100 % of APS type-1 patients.
Hypoparathyroidism, causing loss of parathyroid function (hypoparathyreosis) is found in 76–93 % of APS type-1 patients.
Autommune Addison’s disease, also called autoimmune adrenalitis, is found in 72-100 % of APS type-1 patients. Still many of them die for unrecognized or late diagnosed autoimmune Addison’s disease, so regular follow-up for children in suspicion of APS type-1 (with CMC or/and hypoparathyroidism) is necessary.4
Other assocated disorders that may develop, but are not required for diagnosis, include: vitiligo, premature menopause, pernicious anemia, parathyroid gland failure, alopecia, and celiac disease. Thyroid disease rarely occurs.5
APS type-2 is linked to the inheritance of HLA antigens on chromosome 6 and appears to be autosomal dominant with incomplete penetrance. This suggests the contribution of environmental factors, such as bacterial and viral infections, medications, psychological factors, etc.6It does not have an identified mutation of the AIRE gene.
Diagnosis criteria for autoimmune polyglandular syndrome type-2 includes these two disorders:
Autommune Addison’s disease combined with
Autoimmune thyroid disease (thyroid atrophy, hypertrophic goiter related to Hashimoto’s thyroiditis, Graves’ disease, asymptomatic autoimmune thyroiditis)6 and/or type I diabetes mellitus. The conditions may occur in any order.
Polyglandular autoimmune syndrome type-2 is also known as Schmidt’s syndrome when adrenalitis (adrenal insufficiency) is associated with thyroiditis and Carpenter’s syndrome for adrenal insufficiency with hypoparathyreosis (impaired function of parathyroid glands).
Other disorders that may develop, but are not required for diagnosis, include: type 1 diabetes (50%), frequently gonadal failure or vitiligos, also celiac disease, autoimmune hepatitis, alopecia, pernicious anemia, and myasthenia gravis.7 Decades may arise between the onset of one disease and the onset of the second in the same patient.8
Therapy of APS type-2 consists of hormone replacement therapy for each separate condition, except that treatment for adrenal insufficiency must be given before thyroid therapy is started when the conditions occur together.9 Thyroxin replacement may induce life-threatening adrenal failure in a patient with untreated Addison’s disease. Thus, in case of doubt hydrocortisone should be given before the thyroxine administration is started.10
APS type-3 has a strong genetic background. Diagnosis criteria for autoimmune polyglandular syndrome type-3 involves these conditions:
Autoimmune thyroiditis that occurs with another organ-specific autoimmune disease, but not with autoimmune Addison’s disease, and
Other autoimmune diseases can include diabetes mellitus, pernicious anemia, vitiligo, alopecia, myasthenia gravis, celiac disease, and Sjögren’s syndrome. The most common APS type-3 combination is autoimmune disease of thyroid gland and pernicious anemia.11
Who is Affected in the General Population?
APS type-1 is usually apparent in childhood with the incidence of 1 in100,000 persons. It is more common among Finns (1 in 25,000), Sardinians (1 in 14,000), and Iranian Jews (1 in 6,500 to 1 in 9,000). The age of onset is usually early childhood, but new symptoms can develop throughout life. It affects both sexes equally.
APS type-2 has a peak onset in middle age, although the first signs usually develop between 20–30 years of age. Its prevalence is 1 in 20,000 persons. It is three times more frequent among women than men.12
APS type-3 is most frequent among middle-aged women.7
What Is Autoimmune Polyglandular Syndrome In Celiac Disease and/or Gluten Sensitivity?
Sources:
Wémeau JL, Proust-Lemoine E, Ryndak A, Vanhove L. Thyroid autoimmunity and polyglandular endocrine syndromes. Hormones (Athens). 2013 Jan-Mar;12(1):39-45. [↩]
Femiano P, Castaldo V, Iossa C. Complex family association in autoimmune polyendocrine syndrome. Minerva Pediatrica. Apr 2003;55(2):163-70. [↩]
Wémeau JL, Proust-Lemoine E, Ryndak A, Vanhove L. Thyroid autoimmunity and polyglandular endocrine syndromes. Hormones (Athens). 2013 Jan-Mar;12(1):39-45. [↩]
Wémeau JL, Proust-Lemoine E, Ryndak A, Vanhove L. Thyroid autoimmunity and polyglandular endocrine syndromes. Hormones (Athens). 2013 Jan-Mar;12(1):39-45. [↩]
Wémeau JL, Proust-Lemoine E, Ryndak A, Vanhove L. Thyroid autoimmunity and polyglandular endocrine syndromes. Hormones (Athens). 2013 Jan-Mar;12(1):39-45. [↩] [↩]
MAJERONI BA and PATEL P. Autoimmune Polyglandular Syndrome, Type II. Am Fam Physician. 2007 Mar 1;75(5):667-670. [↩]
Lipowsky C, Schorl-Schweikardt BA, Kehl O, Brändle M. 19-year-old patient with adrenal cortex insufficiency–only the tip of the iceberg. Polyendocrine autoimmune syndrome type II (Schmidt syndrome). Praxis (Bern 1994). 2008 Jan 23;97(2):77-81. [↩]
Van den Driessche A, Eenkhoorn V, Van Gaal L, De Block C. Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. Neth J Med. 2009 Dec;67(11):376-87. [↩]
Hypocalcemia, or low plasma calcium, means the level of calcium in blood is too low to meet metabolic needs of the body for calcium.
Low blood calcium is characterized by bone and tooth demineralization (loss of calcium causing weak teeth and fragile bones), and these impaired functions: nerve conduction, muscle contraction, blood clotting, blood pressure regulation, glycogen to glucose conversion, many hormone actions, many enzyme activities, and acetylcholine production.
Q: Where is calcium found in the body?
A: Calcium is the most abundant mineral in the body, with 99% residing in bones and teeth where it constitutes 40% of skeletal bone weight along with 45% phosphorus. As a component of bone (hard tissue), calcium fulfills a structural role to maintain body size and act as attachments for musculoskeletal tissues. The remaining 1% of calcium is present in blood and soft tissues.
Calcium levels in the blood are maintained within very strict limits by dietary intake, hormonal regulation by the parathyroid gland and a rapidly exchangeable pool in bone tissue.
What Is Hypocalcemia In Celiac Disease and/or Gluten Sensitivity?
Laryngospasm is an acute disorder of the larynx that is characterized by life-threatening spasms of the muscles of the larynx located in the throat.
Laryngospasm is a rare feature of hypocalcemia (low blood calcium level) characterized by severe alteration in nerve conduction and muscle contraction.
What Is Laryngospasm In Celiac Disease and/or Gluten Sensitivity?
A menstrual disorder that occurs regularly during the last week of the luteal phase and starts to subside a few days before menstruation begins. PMS is an atypical symptom of celiac disease involving deficiencies of…
A metabolic bone disorder characterized by diminished bone mass (density) with retention of normal cell appearance, but fragile strength, and high bone turnover caused by deficiency of calcium and vitamin D in particular and other…
Impaired status of muscle function mainly resulting from nutritional deficiencies including any of these: protein, magnesium, thiamin (B1), niacin (B3), potassium, phosphorus, selenium, and vitamin D, or due to chronic fatigue syndrome or hypoglycemia, and if…
A feature of osteomalacia characterized by painful proximal muscle weakness involving the thighs and upper arms and hyperreflexia resulting from deficiencies of phosphorus and vitamin D.
What Is Neutropenia?
