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The cause is currently unknown. The histology is suggestive of an autoimmune reaction. The high rate of relapses as well as relatively high proportion of bilateral cases is highly suggestive of a systemic predisposition.
Presently most evidence points towards an important role of elevated prolactin levels or overt hyperprolactinemia with additional triggers such as local trauma or irritation. Alpha 1-antitrypsin deficiency was documented in one case, interferon-alpha therapy in another case. Similar cases of granulomatous mastitis were reported in IgG4-related disease though the exact relationship to IGM remains to be elucidated. Other contributing factors of IGM were investigated such as oral contraceptives usage. Many cases were reported after use of prolactin elevating medications such as antipsychotics.
Elevated prolactin levels have the direct effects of increasing secretory activity of breast lobules, maintaining tight junctions of the ductal epithelium, preventing involution of the breast gland after weaning and are known to stimulate the immune system, contributing to both physiological and pathological granulomatous lesions and non-caseating granulomas. PRL is also secreted locally in the breast and local secretion by lymphocytes may be enhanced during inflammatory reactions.
Autoimmune reaction to extravasated fat and protein rich luminal fluid (denaturized milk) resulting from the secretory activity is assumed to be one of the triggers of IGM. Several other hormones can contribute to PRL signaling in the breast gland, high levels of insulin caused for example by peripheral insulin resistance (resulting from pregnancy, gestational diabetes or developing diabetes mellitus type 2) will enhance the galactogenic and antiapoptotic effects of PRL and growth hormone by acting synergistically with IGF-1.
Idiopathic granulomatous mastitis is defined as granulomatous mastits without any other attributable cause such as those above mentioned. It occurs on average two years and almost exclusively up to six years after pregnancy, usual age range is 17 to 42 years. Some cases have been reported that were related to drug induced hyperprolactinemia.
Exceptionally rarely it has been diagnosed during pregnancy and in men.
OFG is uncommon, but the incidence is increasing. The disease usually presents in adolescence or young adulthood. It may occur in either sex, but males are slightly more commonly affected.
Palpation thyroiditis refers to the development of thyroid inflammation due to mechanical damage to thyroid follicles.This can occur by vigorous repeated palpation (as with thyroid examination) or surgical manipulation (as can occur with radical neck dissection). It is a type of subacute thyroiditis. Pathology shows multifocal granulomatous folliculitis. T cells predominate compared to B cells. There may be initial transient hyperthyroidism due to leakage of preformed thyroid hormone in blood.
The cause of the condition is unknown. The disease is characterized by non-caseating granulomatous inflammation. That is, the granulomas do not undergo the caseating ("cheese-like") necrosis typical of the granulomas of tuberculosis.
There is disagreement as to whether OFG represents an early form of Crohn's disease or sarcoidosis, or whether it is a distinct, but similar clinical entity. Crohn's disease can affect any part of gastrointestinal tract, from mouth to anus. When it involves the mouth alone, some authors refer to this as "oral Crohn's disease", distinguishing it from OFG, and others suggest that OFG is the same condition as Crohn's disease when it presents in the oral cavity.
OFG may represent a delayed hypersensitivity reaction, but the causative antigen(s) is not identified or varies form one individual to the next. Suspected sources of antigens include metals, e.g. cobalt, or additives and preservatives in foods, including benzoates, benzoic acid, cinnamaldehyde, metabisulfates, butylated hydroxyanisole, dodecyl gallate, tartrazine, or menthol, Examples of foods which may contain these substances include margarine, cinnamon, eggs, chocolate or peppermint oil.
Some suggest that infection with atypical mycobacteria could be involved, (paratuberculosis), and that OFG is a reaction to mycobacterial stress protein mSP65 acting as an antigen.
In response to an antigen, a chronic, submucosal, T cell mediated inflammatory response occurs, which involves cytokines (e.g. tumor necrosis factor alpha), protease-activated receptors, matrix metalloproteinases and cyclooxygenases. The granulomas in OFG form in the lamina propria, and may form adjacent to or within lymphatic vessels. This is thought to cause obstruction of lymphatic drainage and lymphedema which is manifest as swelling clinically.
There may be a genetic predisposition to the condition. People who develop OFG often have a history of atopy, such as childhood asthma or eczema.
Hypophysitis refers to an inflammation of the pituitary gland. Hypophysitis is rare and not fully understood.
Hypophysitis is commonly known as Lymphocytic Hypophysitis because the lymphocytic infiltration was limited to the anterior pituitary.
The varicella-zoster virus antigen was found in 74% of temporal artery biopsies that were GCA-positive, suggesting that the VZV infection may trigger the inflammatory cascade.
The disorder may coexist (in a half of cases) with polymyalgia rheumatica (PMR), which is characterized by sudden onset of pain and stiffness in muscles (pelvis, shoulder) of the body and is seen in the elderly. GCA and PMR are so closely linked that they are often considered to be different manifestations of the same disease process. Other diseases associated with temporal arteritis are systemic lupus erythematosus, rheumatoid arthritis, and severe infections.
Giant-cell arteritis can involve branches of the aorta as well, leading to an aortic aneurysm or dissection. For this reason, patients should be followed with serial chest X-rays.
Giant-cell arteritis (GCA), also called temporal arteritis, is an inflammatory disease of blood vessels. Symptoms may include headache, pain over the temples, flu-like symptoms, double vision, and difficulty opening the mouth. Complication can include blockage of the artery to the eye with resulting blindness, aortic dissection, and aortic aneurysm. GCA is frequently associated with polymyalgia rheumatica.
The cause is unknown. The underlying mechanism involves inflammation of the small blood vessels that occur within the walls of larger arteries. This mainly affects arteries around the head and neck, though some in the chest may also be affected. Diagnosis is suspected based on symptoms, blood tests, and medical imaging, and confirmed by biopsy of the temporal artery. However, in about 10% of people the temporal artery is normal.
Treatment is typically with high doses of steroids, such as prednisone. Once symptoms have resolved the dose is then decreased by about 15% per month. Once a low dose is reached, the taper is slowed further over the subsequent year. Other medications that may be recommended include bisphosphonates to prevent bone loss and a proton pump inhibitor to prevent stomach problems.
It affects about 1 in 15,000 people over the age of 50 a year. The condition typically only occurs in those over the age of 50 being most common among those in their 70s. Females are more often affected than males. Those of northern European descent are more commonly affected. Life expectancy is typically normal. The first description of the condition occurred in 1890.
The prognosis for hypophysitis was variable for each individual. The depending factors for hypophysitis included the advancement of the mass on the Sella Turcica, percentage of fibrosis, and the body's response to corticosteroids. Through the use of Corticosteroids, the vision defects tend to recover when the gland size began to decrease. The prognoses of the limited number of reported cases were usually good.
Subacute thyroiditis is a form of thyroiditis that can be a cause of both thyrotoxicosis and hypothyroidism. It is uncommon and can affect individuals of both sexes and people of all ages. The most common form, subacute granulomatous, or de Quervain's, thyroiditis manifests as a sudden and painful enlargement of the thyroid gland accompanied with fever, malaise and muscle aches. Indirect evidence has implicated viral infection in the aetiology of subacute thyroiditis. This evidence is limited to preceding upper respiratory tract infection, elevated viral antibody levels, and both seasonal and geographical clustering of cases. There may be a genetic predisposition.
Nishihara and coworkers studied the clinical features of subacute thyroiditis in 852 mostly 40- to 50-year-old women in Japan. They noted seasonal clusters (summer to early autumn) and most subjects presented with neck pain. Fever and symptoms of thyrotoxicosis was present in two thirds of subjects. Upper respiratory tract infections in the month preceding presentation were reported in only 1 in 5 subjects. Recurrent episodes following resolution of the initial episode were rare, occurring in just 1.6% of cases. Laboratory markers for thyroid inflammation and dysfunction typically peaked within one week of onset of illness.
Types include:
- Subacute granulomatous thyroiditis (De Quervain thyroiditis)
- Subacute lymphocytic thyroiditis
- Postpartum thyroiditis
- Palpation thyroiditis
The symptoms depend on what part of the pituitary is affected. Lymphocytic adenohypophysitis (LAH) occurs when the anterior pituitary cells are affected by autoimmune inflammation resulting in either no symptoms, adrenal insufficiency (if the ACTH producing cells are affected), hypothyroidism (if the TSH producing cells are damaged), or hypogonadism (if the LH and/or FSH producing cells are involved). In some cases, the presence of inflammation within the pituitary gland leads to interruption of dopamine flow from the hypothalamus into the pituitary causing high levels of the hormone prolactin and, often as a consequence, milk production from the breasts (in older girls and women). Lymphocytic Infundibuloneurohypophysitis (LINH) occurs when the posterior pituitary is affected resulting in diabetes insipidus. Both LAH and LINH may also lead to symptoms of an intracranial mass such as headache or disturbance of vision, i.e. bitemporal hemianopia.
The pituitary produces multiple hormones relating to various metabolic functions. Sufficiently low production of certain pituitary hormones can be fatal resulting in the failure of the thyroid or adrenal glands.
It is estimated that, typically, it takes from 12 to 40 years for autoimmune destruction to present symptoms. However, there have been cases of isolated attacks as a result of drug reactions (i.e., use of blocking antibody ipilimumab) or idiopathic events that have presented symptoms which may disappear after relatively short term treatment (i.e., 1 year on corticoids or other immune suppressants). However, more rapid development of the disorder is the rule when it occurs during, or shortly after, pregnancy (even after miscarriage or abortion). Indeed, autoimmune hypophysitis occurs more commonly during and shortly after pregnancy than at any other time.
It is caused by "Klebsiella rhinoscleromatis"—subspecies of
"Klebsiella pneumoniae"— a gram-negative, encapsulated, nonmotile, rod-shaped bacillus (diplobacillus), member of the Enterobacteriaceae family. It is sometimes referred to as the "Frisch bacillus," named for Anton von Frisch who identified the organism in 1882. It is contracted directly by droplets or by contamination of material that is subsequently inhaled.
It is not lethal in nature and is responsive to tetracycline or ciprofloxacin. Surgical treatment include rhinoplasty. However, if left untreated the disease can lead to sepsis, bleeding, or other chronic conditions that can be fatal.
Alcoholism is mistakenly attributed as a cause of this issue. Alcohol however may cause increased flushing in those affected.
80% of patients with pituitary antibodies also have antibodies to thyroid gland or its hormones. Likewise, 20% of autoimmune thyroid patients also have pituitary antibodies. It follows that a subset of thyroid patients may have a disease related to autoimmune hypophysitis. Recent research has focused on a defect at the CTLA-4 gene which, coupled with other factors, may result in autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.
A foreign-body granuloma occurs when a foreign body (such as a wood splinter, piece of metal, glass etc.) penetrates the body's soft tissue followed by acute inflammation and formation of a granuloma. In some cases the foreign body can be found and removed even years after the precipitating event.
Granuloma is an inflammation found in many diseases. It is a collection of immune cells known as histiocytes (macrophages). Granulomas form when the immune system attempts to wall off substances it perceives as foreign but is unable to eliminate. Such substances include infectious organisms including bacteria and fungi, as well as other materials such as keratin and suture fragments.
Uveitis may be an immune response to fight an infection inside the eye. While representing the minority of patients with uveitis, such possible infections include:
- brucellosis
- leptospirosis
- Lyme disease
- presumed ocular histoplasmosis syndrome
- syphilis
- toxocariasis
- toxoplasmic chorioretinitis
- tuberculosis
- Zika fever
Frontal Fibrosing Alopecia has been most often reported in post-menopausal women with higher levels of affluence and a negative smoking history. Autoimmune disease is found in 30% of patients.
Although there is sometimes a preceding viral infection, or skin or eye trauma, the exact underlying initiator of VKH disease remains unknown. However, VKH is attributed to aberrant T-cell-mediated immune response directed against self-antigens found on melanocytes. Stimulated by interleukin 23 (IL-23), T helper 17 cells and cytokines such as interleukin 17 (IL-17) appear to target proteins in the melanocyte.
Uveitis is usually an isolated illness, but can be associated with many other medical conditions.
In anterior uveitis, no associated condition or syndrome is found in approximately one-half of cases. However, anterior uveitis is often one of the syndromes associated with HLA-B27. Presence of this type of HLA allele has a relative risk of evolving this disease by approximately 15%.
The most common form of uveitis is acute anterior uveitis (AAU). It is most commonly associated with HLA-B27, which has important features: HLA-B27 AAU can be associated with ocular inflammation alone or in association with systemic disease. HLA-B27 AAU has characteristic clinical features including male preponderance, unilateral alternating acute onset, a non-granulomatous appearance, and frequent recurrences, whereas HLA-B27 negative AAU has an equivalent male to female onset, bilateral chronic course, and more frequent granulomatous appearance. Rheumatoid arthritis is not uncommon in Asian countries as a significant association of uveitis.
The cause is unknown, but it may be partly a genetic trait. Aging and environmental factors may also contribute to the appearance.
Tuberculous dactylitis is a skeletal manifestation of tuberculosis, one of the commonest bacterial osteitis. It affects children more often than adults. The first radiological description of the condition is credited to Feilchenfeld in 1896; however, the first histological description was given by Rankin in 1886. Multiple bones are involved in children and usually only a single bone is involved in adults suffering from tuberculous dactylitis. Tuberculous dactylitis affects the short tubular bones of the hands and feet in children. It often follows a mild course without fever and acute inflammatory signs as opposed to acute osteomyelitis. There may be a gap of a few months to 2 to 3 years from the time of initial infection to the point of diagnosis.
Spina ventosa is the term given for tuberculous dactylitis. Nearly 85% of the patients of spina ventosa are below 6 years of age.The bones of hands are more commonly involved than those of the feet. Proximal phalanx of the index and middle fingers are the commonest sites of involvement.Up to nearly 7% of children with pulmonary tuberculosis may develop this condition. Spread to the skeletal system is believed to occur via blood and lymphatics.
In the pediatric age group, the marrow in the phalangeal bones are still active, a conducive place for the tuberculous bacilli to multiply. Slowly, the whole marrow space gets involved and this underlying granulomatous disease leads to expansion of the overlying soft cortex. Finally there is a fusiform dilation of the bone, with thinned out cortex and destruction of the marrow space leading to a balloon like shape; this cystic type of expansion of the bone is termed as spina ventosa.
There are currently no studies detailing the long term outcome of chronic granulomatous disease with modern treatment. Without treatment, children often die in the first decade of life. The increased severity of X-linked CGD results in a decreased survival rate of patients, as 20% of X-linked patients die of CGD-related causes by the age of 10, whereas 20% of autosomal recessive patients die by the age of 35.
Recent experience from centers specializing in the care of patients with CGD suggests that the current mortality has fallen to under 3% and 1% respectively.
CGD was initially termed "fatal granulomatous disease of childhood" because patients rarely survived past their first decade in the time before routine use of prophylactic antimicrobial agents. The average patient now survives at least 40 years.