The spleen is the darkish oval organ in the lower middle of this photo.
What Is Hyposplenism?
H yposplenism is the condition resulting from having lost spleen tissue, called atrophy of the spleen. Spleen atrophy impairs splenic functions or activities because there are insufficient tissues to do the work required.
Q: What splenic functions are impaired?
A: The spleen, apart from acting as a phagocytic filter, thus removing aging and damaged cells, is crucial in regulating immune homeostasis by linking innate and adaptive immunity, and in protecting against infections by encapsulated bacteria.1
Impaired function of the spleen therefore increases risk of infections with encapsulated bacteria because of inability to mount a proper defense and to filter and remove bacteria from the circulation.
The spleen is a highly vascular and solid organ about the size of a fist. It has a delicate structure inside that is enclosed by fibrous, elastic layers consisting of connective tissue.
The tissues within are made up of two different types of tissues, called white pulp and red pulp. White pulp carries out lymphoid functions. Red pulp filters and cleanses the blood. The spleen is situated above the stomach on the left side of the upper abdomen and firmly fixed in place by ligaments and ribs.
The spleen is an important organ of the lymph system, having the largest collection of lymph tissue in the body. It functions to produce antibodies (immunoglobulins) and white blood cells (T-cells and B-cells), help control the amount of blood in the body, keep body fluids in balance, destroy and filter out old and damaged cells2 and salvage the iron needed for producing new blood cells, and lastly, clear bacteria through production of substances that enable phagocytosis (engulfing bacteria and other unwanted particles, such as antigens, from blood).
Children and adults with hyposplenism are at risk for overwhelming infections. Management of hypospenism is directed towards preventing pneumonia by immununization against pneumonia and meningitis and treating bacterial infections as they arise, which may require hospitalization. For some patients, life-long treatment with antibiotics, such as erythromycin and penicillin, are recommended.
What Is Hyposplenism In Celiac Disease and/or Gluten Sensitivity?
Sources:
Di Sabatino A, Brunetti L, Carnevale Maffè G, Giuffrida P, Corazza GR. Is it worth investigating splenic function in patients with celiac disease? World J Gastroenterol. 2013 Apr 21;19(15):2313-8. doi: 10.3748/wjg.v19.i15.2313. [↩]
H ypokalemic rhabdomyolysis is an acute and sometimes fatal disease due to its rapid progression of muscle destruction when untreated.
It is characterized by the accumulation of by-products of skeletal muscle destruction in the renal (kidney) tubules and producing acute kidney failure caused by rapid potassium loss.
This condition puts you in bed because the legs muscles cannot support the body and arms are too weak to move.
What Is Hypokalemic Rhabdomyolysis In Celiac Disease and/or Gluten Sensitivity and Dermatitis Herpetiformis?
M uscle weakness is the impaired status of muscle function characterized by decreased or low muscle strength and inability to perform normal work such as lifting a pot off the stove.
Q: How do muscles work?
A: Muscles do their work by contracting or shortening. For example, to move the foot up and down at the ankle, muscles attached to the foot by tendons must contract to shorten or relax to return to their resting length. Calf muscles contract to point the foot down (flexion) while the shin muscles relax (extension). For the foot to point up, calf muscles relax while the opposing shin muscles contract.
Each muscle is made up of individual muscle fibers. A muscle fiber is a long cylindrical cell that contains many nuclei, mitochondria, and sarcomeres. Each muscle fiber is surrounded by a thin layer of connective tissue called the endomysium.
Approximately 20–80 of these muscle fibers are grouped together in a parallel arrangement called a muscle fascicle or fiber bundle that is encapsulated by a perimysium. A distinct muscle is formed by enveloping a large number of muscle fascicles in a thick collagenous external sheath extending from the tendons called the epimysium.1
Muscles fall into three types:
Voluntary muscles. These muscles, also called skeletal, we can control by will. Voluntary muscles function by contracting their fibers to draw one part of the body toward another in flexion while opposing muscles that extend or pull a body part away from another. They move our bones to perform activities such as walking to get somewhere, chewing to eat food, lifting to do work, and moving the eyeball to look at something.
Involuntary muscles. These muscles work independently of our conscious control. They are needed for internal organs, sphincters, and other parts to do their work, such as peristalsis in the gut that must function at all times to digest and move food, the squirting of bile juice into the duodenum by the Sphincter of Odi in the presence of fat eaten, and action of the pupil to see.
Cardiac muscles. These muscles are specialized to keep the heart functioning at all times.
Muscle weakness can involve all types of muscles.
What Is Muscle Weakness In Celiac Disease and/or Gluten Sensitivity?
Deep Vein Thrombosis in the Right Leg with Swelling and Redness. Courtesy wikipedia.
What Is Antiphospholipid Syndrome?
Antiphospholipid syndrome (APS) is an autoimmune disease and a blood clotting disorder characterized by these clinical and laboratory criteria:
Clinical criteria – recurrent vascular thrombosis (clots in veins/arteries) from hypercoagulability (abnormal excessive clotting) and/or recurrent complications of pregnancy that include loss of the fetus (miscarriage) and pre-eclampsia or eclampsia.
Laboratory criteria – persistently elevated anticardiolipin, anti–beta-2 glycoprotein I, and/or lupus anti-coagulant antibodies in blood.
In antiphospholipid syndrome autoantibodies are produced by the body and directed against negatively charged phospholipids that are found in the outer layer of cell membranes and platelets. B2-glycoprotein-I (a protein in blood plasma) has been found as a major target antigen for antiphospholipid antibodies.
Q: Are phospholipids important in the body?
A: Yes. Phospholipid molecules are an essential part of cell membranes. They form a barrier around cells that protect the cell, allow movement of oxygen in and carbon dioxide out of the cell, and regulate other small molecules through the cell wall. Because phospholipids are widespread in the body, this disorder can produce a large variety of symptoms and affect many organs.
One severe effect of APS is the development of a blood clot in a vein deep in the arm or leg, called deep vein thrombosis (DVT). DVT can cause pain, swelling, redness, or increased warmth in the affected limb. Deep vein clots can break off, travel to the lungs, and cause pulmonary embolism.1 Pulmonary embolism is a medical emergency.
Treatment is with anticoagulant medications and blood monitoring.
What Is Antiphospholipid Syndrome In Celiac Disease and/or Gluten Sensitivity?
Drawing shows changes in airways during asthma attack. wikipedia
What Is Asthma?
Asthma is a chronic immune respiratory condition characterized by narrowing and inflammation of the lung airways (large bronchi, bronchial tubes and small bronchioles) in response to an allergen as the trigger or stimulus. As such, asthma occurs in episodes and does not result in progressive loss of pulmonary function.
During an asthma attack, airways constrict, trapping air so lungs become overinflated. Normally, bronchial airways bring air to millions of air sacs that are attached to the ends of bronchioles. Air sacs, called alveoli, are only one cell thick to allow for rapid exchange of gases.
That is, oxygen from air breathed into the sacs moves into the bloodsteam and carbon dioxide is released from the bloodstream to air that is breathed out of air sacs.
The outer walls of bronchioles are made up of muscles which, in the process of breathing, normally contract on expiration to help expel air and then relax. During an asthma attack, these muscles abnormally constrict, impairing airflow into and out of the alveoli. This is called bronchospasm.
Common allergens that cause inflammation include airborne dust mite feces, mold, and pollen and foods such as wheat, cow’s milk, eggs, and peanuts. Non-allergenic triggers include exercise, air pollution, smoking, and viral respiratory infection.
Q: What effect does inflammation have on the lungs?
A: Inflammation causes local tissue edema or swelling of the bronchioles and mucus formation. Inflammation with increased mucus secretions and edema narrows the airways that connect to alveoli which makes breathing difficult. Two things happen:
Inflammation impairs exchange of gases in alveoli, resulting in lack of sufficient oxygen (O2) for body cell functions, called hypoxia, and build-up of carbon dioxide (CO2) in blood, called CO2 retention.
Inflammation narrows passageways because of swelling, which reduces the movement of air to and from the alveoli through the airways, and this puts stress on the right side of the heart.
Treatment is aimed at controlling bronchospasm and reducing inflammation. Untreated asthma can be disabling and life threatening.
What Is Asthma In Celiac Disease and/or Gluten Sensitivity?
Each antibody binds to a specific antigen; an interaction similar to a lock and key. Courtesy Wikipedia.
What Are Autoimmune Disorders?
A utoimmune disorders refer to those conditions that involve an abnormal immune attack on the body’s own tissues perpetuated by the production of autoantibodies directed against the body, or “self.” Auto means self.
Q: Why does the immune system attack the body?
A: The exact answer is not yet known why the immune system turns against body tissue or “self.”
Normally, the immune system protects the body from harmful substances and pathogens and produces antibodies against the offending foreign substances, called antigens, to get rid of them. The immune system (humoral) thereafter remembers all antigens and is ready for the next encounter should it happen.
Production of autoimmune antibodies iscatastrophic because there is no turning off the readiness to attack a remembered threat (antigen) which is unfortunately “self.”
Yes, steroids and anti-inflammatory drugs can control symptoms, but nothing can undo the memory programmed into the immune system to produce autoantibodies. There is an enormous research effort ongoing for the answer.
Autoimmune disorders cover a wide range of diseases that may target only a particular organ, such as autoimmune hepatitis (liver), while others are systemic because the autoantibodies target a particular tissue that is part of more than one organ, such as scleroderma (connective tissue).
Autoimmune diseases as a group affect approximately 8.5% of people worldwide.
What Are Autoimmune Disorders 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. [↩]
I gA deficiency (IgAD) is an immunodeficiency disease characterized by lack of immunoglobulin A type antibody production, called IgA antibody, with no detectable levels in blood or secretions.
Q: What is an IgA antibody?
A: IgA is an antibody of the immune system that is secreted by plasma cells (specialized white blood cells) through epithelial cell linings of mucosal surfaces into mucosa secretions to protect the lining from microbe invasion.
In fact, immunoglobulin class A is the main protein of the mucosal immune system. This includes mucosa of the eye surface, digestive tract, respiratory tract, urinary tract, and genital tract.
Both major histocompatibility complex (MHC) and non-MHC genes contribute to susceptibility to the disease. The former genes appear to be located in different parts of the MHC region depending on the HLA haplotype. The latter show a marked overlap with genes associated with a variety of autoimmune disorders including Graves’ disease, systemic lupus erythematosus, type 1 diabetes and celiac disease, suggesting common pathophysiological mechanisms. The involvement of genes associated with autoimmunity may suggest that IgAD in itself is an autoimmune disease.1
IgA deficiency may progress into a common variable immunodeficiency (CVID).2
What Is IgA Deficiency (IgAD) In Celiac Disease and/or Gluten Sensitivity?
Sources:
Wang N, Hammarström L. IgA deficiency: what is new? Curr Opin Allergy Clin Immunol. 2012 Dec;12(6):602-8. doi: 10.1097/ACI.0b013e3283594219. [↩]
Binek A, Jarosz-Chobot P.Selective immunoglobulin A deficiency. Pediatr Endocrinol Diabetes Metab. 2012;18(2):76-8. [↩]
Testing the Eye for Tear Production (L) and Damage to Conjunctiva from Dryness (R).
What Is Sjögren’s Syndrome?
S jögren’s syndrome is a systemic inflammatory autoimmune disease with a chronic, progressive course that primarily attacks the lacrimal glands of the eye and the salivary glands of the mouth, which are exocrine glands. Exocrine glands secrete the substances they produce through a duct.
Sjögren’s syndrome is ordinarily characterized by dysfunction of the lacrimal glands to produce tears causing dry eye and the salivary glands to produce saliva causing dry mouth, but is not limited by or to these features.
Besides involvement of these exocrine glands, there may be involvement of other parts of the body, termed extraglandular, which may be more severe than eye or mouth features.
There is not yet agreement on classifying Sjögren’s syndrome. Primary and secondary are the two forms generally accepted.1 Both forms can cause mild to severe disease, called the spectrum:
Primary Sjögren syndrome. Disease occurs without involvement of other linked autoimmune disorders. In addition to the eyes and mouth, the nose, throat and skin may also be affected and joints, lungs, kidneys, blood vessels, digestive organs and nerves as well.2 Systemic manifestations (other than eyes and mouth) concern a third of patients, including lymphoma in 5% of the patients.3
Secondary Sjögren’s syndrome. Disease complicates other autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, primary biliary cirrhosis, and celiac disease.
Diagnosis of Sjögren’s syndrome is made by most doctors based on Schimer’s test for tears and unstimulated whole salivary flow to assess objective eye and oral involvement, since these are the tests most physicians use in clinical practice.4 Specific antibody tests would be positive for anti-Ro (SSA)/anti-La (SSB) autoantibodies. Sjögren’s syndrome should also be considered when extraglandular manifestations such as vasculitis, polyneuropathy or arthritis occur, even when the patients do not complain of dry eyes and mouth.5
There is no cure for Sjögren’s syndrome. Treatment is aimed to diminish symptoms. For example, steroids and Ibupropen are used to decrease inflammation and pain in joints. Artificial tears and ointments are used for dry eye.
Most people who develop Sjogren’s syndrome are older than 40 years. Nine of ten people with Sjögren’s syndrome are women.2
What Is Sjögren’s Syndrome In Celiac Disease and/or Gluten Sensitivity?
Sources:
Huang YF, Cheng Q, Jiang CM, An S, Xiao L, Gou YC, Yu WJ, Lei L, Chen QM, Wang Y, Wang J. The immune factors involved in the pathogenesis, diagnosis, and treatment of Sjogren’s syndrome. Clin Dev Immunol. 2013;2013:160491. doi: 10.1155/2013/160491. Epub 2013 Jul 9. [↩]
Fazaa A, Bourcier T, Chatelus E, Sordet C, Theulin A, Sibilia J, Gottenberg JE. Classification criteria and treatment modalities in primary Sjögren’s syndrome. Expert Rev Clin Immunol. 2014 Apr;10(4):543-51. doi: 10.1586/1744666X.2014.897230. [↩]
Cornec D, Saraux A, Cochener B, Pers JO, Jousse-Joulin S, Renaudineau Y, Marhadour T, Devauchelle-Pensec V. Level of agreement between 2002 American-European Consensus Group and 2012 American College of Rheumatology classification criteria for Sjogren’s syndrome and reasons for discrepancies. Arthritis Res Ther. 2014 Mar 19;16(2):R74. [↩]
Witte T. Pathogenesis and diagnosis of Sjögren’s syndrome. Z Rheumatol. 2010 Feb;69(1):50-6. doi: 10.1007/s00393-009-0519-2. [↩]
Image showing butterfly rash typical of SLE. Courtesy JAMA.
What Is Systemic Lupus Erythematosus?
S ystemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that is characterized by involvement of multiple organs due to the production of antibodies to components of the cell nucleus.1 SLE has an unpredictable course of acute flare-ups and remissions.
Severity depends on the extent of organs affected with skin and nail involvement, called discoid lupus, being the least serious and inflammmation of the kidney, called lupus nephritis, being the worst.
Nevetheless, a classic presentation is development of a rash over the cheeks and nose that resembles a butterfy with wings spread hence the name “butterfly rash.”
Symptoms are many and varied depending on the tissues affected and are often not specific, for example hair loss has a variety of causes. Symptoms can be confused by co-existence with other autoimmune disease such as Sjogren’s syndrome.
Systemic lupus erythematosus should be managed by a specialist. Symptoms can be controlled with steroid therapy, but this disease can be a cause of premature death mainly from active disease, organ failure (e.g., kidneys), infection, or cardiovascular disease from accelerated atherosclerosis.
Certain common medicines known to cause drug-induced lupus are:
Isoniazid
Hydralazine
Procainamide
Other less common drugs may also cause the condition. These may include:
Anti-seizure medications
Capoten
Chlorpromazine
Etanercept
Infliximab
Methyldopa
Minocycline
Penicillamine
Quinidine
Sulfasalazine
Symptoms tend to occur after taking the drug for at least 3 to 6 months.2
Although there is a strong familial aggregation, the disease is relatively uncommon and most cases are sporadic.1 According to the Center for Diseases (CDC), lupus most commonly affects women of childbearing age but also occurs in infants, children, adolescents, and men with peak occurrence between ages 15 and 40. Blacks (and possibly Hispanics, Asians, and Native Americans) are affected more than Whites.
What Is Systemic Lupus Erythematosus In Celiac Disease and/or Gluten Sensitivity?
