Natural Sarcoid Treatment

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Sarcoidosis Remission and Aden Protocol Overview

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This e-book is a 143 pages long downloadable ebook with hundreds of delicious recipes. But these recipes are not only delicious but have another crucial feature they use only the ingredients that are carefully chosen to meet all the criteria that are critically important in our pursuit of health and sarcoidosis remission. This is how The Sarcoidosis Freedom Cookbook will change your life: You will never eat a meal that triggers your sarcoidosis again. And you very likely did it today. You will gently soothe your endocrine system and shift the ravaging chemical imbalance that is eating away your organs. Kick start the boost of self-healing chemicals that will repair your organs before it's too late. Enjoy delicious meals while knowing every second that you are doing good to your body and getting closer to remission. You won't have to think about where to start in your healing, you will have all the work done for you. When you wake up in the morning you'll feel light and positive, knowing that healing chemicals in your body are doing their work every second. You won't have to spend endless hours in front of your computer or buy nutrition books to know what is completely safe for you. Never again buy another book about diet and health, because you have it all right here and written just for your condition, not general and vague. Start your healing today, without any procrastination. Once again, feel that health and energy you so desperately pursue.

Sarcoidosis Freedom Cookbook Overview

Contents: 143 Page Ebook
Author: Danielle May
Official Website: sarcoidosis-cookbook.com
Price: $17.00

T lymphocytes in sarcoidosis

Lung T cells recovered from the alveolar surface are predominantly of the CD4 phenotype, typically with a CD4 CD8 ratio of 3-10 1 compared with a ratio of 2 1 in healthy individuals (Table 1). Sarcoid and normal lung T cells are almost all memory T cells expressing CD45R0+ CD29 surface markers. Greater numbers of lung T cells express activation markers such as II.-2R, VLA-1 (CD49a) or HLA-DR molecules than circulating T cells. Sarcoid lung T cells demonstrate reduced surface density of the CD3 T cell receptor complex, a hallmark of antigen-stimulated T cells. Consistent with recent activation, greater numbers of lung T cells express the cell cycle-related nuclear antigen Ki67 and a small proportion of lung T cells are spontaneously proliferating. Lung T cells in sarcoidosis spontaneously produce the type 1 cytokines IFNy and IL-2 in vitro. In contrast to the lung, patients with sarcoidosis often demonstrate CD4+ T cell lymphopenia in peripheral blood. Increased numbers of circulating...

Mononuclear phagocytes in sarcoidosis

Sarcoid alveolar macrophages appear activated, producing increased amounts of lysozyme, angiotensin-converting enzyme and reactive oxygen species (Table 1). Reports of enhanced lung macrophage expression of the lFNy-inducible chemokine MIG (monokine-induced by IFNy), provide evidence of cellular activation by IFNy. Sarcoid alveolar macrophages contain a twofold increased density of surface class II MHC (DR,DQ,DP) molecules and the adhesion molecules LFA-1 and ICAM-1. These characteristics probably contribute to the enhanced ability of sarcoid alveolar macrophages to present antigen to autologous T cells compared with normal alveolar macrophages. Sarcoid alveolar macrophages spontaneously produce IL-12, tumor necrosis factor a (TNFa), IL-6, and possibly IL-1, cytokines known to regulate granuloma formation. These cells also release increased amounts of fibronectin and insulin growth factor 1 (IGF-1), molecules important in fibroblast recruitment and replication. In contrast, sarcoid...

Cytokine interactions in sarcoidosis

Substantial evidence indicates that granulomatous inflammation in sarcoidosis is characterized by a predominant type 1 cytokine response. Bronchoalveolar lavage studies demonstrate increased mRNA and protein levels of IFNy, IL-2 and IL-12, low or undetectable levels of IL-4 and IL-5, and normal or low levels of IL-10 in pulmonary sarcoidosis. The known dependence of many granulomatous disorders on type 1 cytokines suggest they function in a similar manner in sarcoidosis. One hypothesis suggests that successful removal of the inciting agent by this TH1-dependent response allows for TFG(3 inhibition of IL-12 and IFNy production and resolution of the disease. If the immune response is ineffective in removing the inciting stimulus or T cell autoimmune responses develop, dysregulated cytokine production driven by a positive feedback loop between IFNy and IL-12 results in maintenance of the granulomatous inflammation. A fibrotic outcome from accumulated tissue injury may theoretically be...

Sarcoidosis

Sarcoidosis is a disease of unknown etiology characterized by epithelioid granulomas and T cell infiltrations in multiple organ systems. The disease most commonly affects the lungs and intrathoracic lymph nodes. Eye and skin involvement is seen in approxi mately 20 of patients, and symptomatic involvement of other organ systems occurs less frequently. Sarcoidosis can be asymptomatic or present in an acute or subacute form. Spontaneous remissions occur in about 50 of cases in other patients. chronic, progressive disease ensues with an overall > 5 mortality rate. Corticosteroids are the mainstay of treatment for threatened organ failure or chronic progressive disease. Sarcoidosis occurs worldwide, primarily in 20-40-year-old adults, with a frequency that varies among different populations and ethnic groups. Epidemiologic and family studies suggest that both environmental and genetic factors play a role in the etiology of sarcoidosis. Recent immunologic studies provide evidence for...

TABLE 2314 Symptoms and Signs of Hypercalcemia

TREATMENT Up to one-third of patients with hypercalcemia have hypokalemia, and in those with malignant disease, more than half the patients may have hypokalemia. Some patients also have hypomagnesemia. The tendency toward hypokalemia and hypomagnesemia will be aggravated by diuresis and should be monitored carefully. A number of modalities are available to treat hypercalcemia (Xakleii2.3.-.1 i5). Mithramycin, calcitonin, and hydrocortisone should be used in severe cases. Mithramycin is a cytotoxic drug that suppresses bone resorption and calcium release from bone. It is infused over 3 h. It is particularly useful in patients with metastatic bone disease. Calcitonin is also an osteoclast inhibitor but less toxic than mithramycin. When used in conjunction with corticosteroids, resistance to calcitonin may be delayed. Glucocorticoids are useful in patients with sarcoidosis, vitamin A or D intoxication, multiple myeloma, leukemia, or breast cancer. They work by inhibiting bone resorption...

Membranous Glomerulopathy

Membranous Glomerulopathy

Membranous glomerulopathy is a major cause of the nephrotic syndrome in adults (1,2). Only in the past decades has it been surpassed by focal and segmental glomerulosclerosis as the main cause of the nephrotic syndrome (3-5). Membranous glomerulopathy develops mostly idiopathically, but can also be seen in relation with and possibly secondary to, among others, hepatitis B, Sjogren's syndrome, transplantation, lupus erythematosus, diabetes mellitus, sarcoidosis, syphilis, exposure to certain drugs and heavy metals (penicillamine, bucillamine, gold, mercuric chloride), and malignancies (10 ), including carcinomas, carcinoids, sarcomas, lymphoma's, and leukemias (2,6-10). The possibility of a malignancy must be considered especially in older patients with membranous glomerulopathy. In these patients it is also imperative to perform urinary immunoelectropho-resis routinely to rule out myeloma and renal primary amyloidosis (AL) (2). Finally, idiopathic membranous glomerulopathy, of which...

Differential Diagnosis

FDCM is distinguished from other specific cardiac diseases and systemic processes resulting in secondary ventricular dilatation and dysfunction 1 eccentric hypertensive cardiomyopathy, ischemic cardiomyopathy, decompensated valvular heart disease, alcoholic cardio-myopathy, and myocarditis. Less common are cardiomyopathies resulting from amyloidosis, sarcoidosis, hemochromatosis and other metabolic disorders, and peripartum cardiomyopathy. Doxorubicin can cause toxic cardiomyopathy.

TABLE 514 Common Causes of Restrictive Cardiomyopathy

The chest x-ray may reveal signs of CHF in the absence of cardiomegaly. Chamber enlargement due to wall thickening, but not dilatation, and nonspecific ST-T-wave changes are usually noted on the ECG. Cardiac conduction disturbances are common in amyloidosis and sarcoidosis. Atrial fibrillation may occur in the setting of atrial enlargement. Low-voltage QRS complexes (QRS amplitude less than 0.7 mV) have been frequently described in patients with restrictive cardiomyopathy secondary to amyloidosis and hemochromatosis.12 TREATMENT AND DISPOSITION Symptoms and signs of CHF, particularly right-sided failure, with a normal-size cardiac silhouette on chest x-ray should prompt a suspicion of underlying restrictive cardiomyopathy, constrictive pericarditis, or diastolic LV dysfunction (most commonly due to ischemic heart disease, hypertension, or age-related changes in ventricular diastolic compliance). Doppler echocardiographic studies and cardiac catheterization with hemodynamic assessment...

Giant cell myocarditis

Myocardial involvement by sarcoid has a range of patterns.10 There may be a diffuse distribution of giant cell granulomas or a single regional mass of sarcoid tissue which is initially expanded in volume, but as fibrosis develops the mass shrinks and may develop into a ventricular aneurysm. Cardiac biopsy to diagnose myocardial sarcoid in a subject with chronic arrhythmias can give a specific positive diagnosis but the false negative rate is high. within a week unless cardiac transplantation is available. There are irregular areas of myocardial necrosis, at the margins of which are large giant cells but no organised granulomas such as occur in sarcoid. No virus has been implicated. The only known association is with autoimmune disease and thymomas, although the majority of cases occur suddenly in subjects who have no other pre-existing disease. Recurrence of the giant cell myocarditis in donor hearts can occur. 10. Silverman K, Hutchins G, Bulkley B. Cardiac sarcoid a...

Specific immunity Antibody

Specific cell-mediated immunity is critical for a protective immune response to C. neoformans and the dimorphic fungi, and is involved in protection against dermatophyte infections. Cell-mediated immunity, rather than intact neutrophil function, is also of primary importance for protection against mucocutaneous candidiasis. These mycoses are seen with increased frequency in patients with the acquired immune deficiency syndrome (AIDS), lymphomas, sarcoidosis, and in those taking immunosuppressive medications such as corticosteroids, cyclophosphamide, or azathioprine. The high incidence of fungal infections in human immunodeficiency virus (HlV)-infected patients is particularly striking. HIV infects CD4J lymphocytes and macrophages, the two cell types whose interactions arc central to the cell-mediated immune response.

VT caused by nonischaemic cardiomyopathy

The mechanisms of sustained monomorphic VT in non-ischaemic cardiomyopathies (including idiopathic cardiomyopathy and valvar heart disease) are diverse. In a series of 26 patients with monomorphic VT the causes were scar related re-entry circuits in 62 of patients, an ectopic focus in 27 , and bundle branch re-entry in 19 .12 Ablation was successful for 60 of the scar related VTs and 86 of the VTs caused by focal automaticity. The difficulties in ablation of scar related VT are similar to those encountered in patients with prior myocardial infarction multiple tachycardias are not uncommon, but reduction in the number of episodes and termination of incessant tachycardia can often be achieved. Successful ablation of scar related VTs in patients with sarcoidosis, scleroderma, Chagas' disease,13 and late after repair of tetralogy of Fallot14 have also been reported, although experience is limited.

Manifestations of HPT

Due to a variety of causes (especially malignancy, Paget disease, sarcoidosis, and milk-alkali syndrome) that must be excluded. Radiographic features of HPT are seen in advanced cases and include decreased bone density, osteitis fibrosa cystica, and the pathognomonic sign of subperiosteal bone resorption on the radial aspect of the phalanges of the second or third digits of the hand.

Management of Hypercalcemia Based on Severity

Other options available for managing mild hypercalcemia in patients with asymptomatic primary hyperparathyroidism include estrogen therapy in postmenopausal women, oral phosphate therapy and the use of bisphosphonates. Other causes of mild hypercalcemia, besides primary hyperparathyroidism, are approached best by dealing directly with the underlying etiology. For example, the hypercalcemia of hyperthyroidism is best handled by treating the hyperthyroidism. The hypercalcemia of granulomatous diseases such as sarcoid and tuberculosis is best handled by treating the disorder itself.

Goals of Therapy for Severe Hypercalcemia

Glucocorticoids can be effective in patients with hematological malignancies, and with hypercalcemias associated with vitamin D excess or sensitivity. Myeloma, lymphoma, sarcoidosis, and other granulomatous diseases are conditions for which glucocorticoids might be particularly effective. In these disorders glucocorticoids inhibit production of various osteoclast-activating factors including calcitriol 7 . In general, patients with nonhematological malignancies and primary hyperparathyroidism do not respond. A dosage of 200-300 mg of hydrocortisone iv or prednisone 50 mg po is given daily for 5-7 days. pathic hypercalciuria denotes the urinary excretion of Ca above normal levels for which there is no readily apparent cause, such as hypercalcemia, sarcoidosis, excessive vitamin D ingestion, glucocorticoid excess, thyrotoxicosis, or immobilization. Reasonable upper limits for 24-hr urinary Ca excretion on an ab lib diet are 250 mg per day in women, 300 mg per day in men, or 4 mg kg day...

Radiosensitivity of lymphoid tissues

Localized irradiation of human thymus, as shown by studies of individuals irradiated prophylactically in infancy for an enlarged thymus to prevent 'status thymolymphaticus', resulted not only in an increased frequency of tumors, but also increased frequency of asthma and other autoimmune disorders (including sarcoidosis, enteritis, thyroiditis and others). However, no impairment of delayed hypersensitivity reactions was noted, suggesting that T cells with regulatory functions are more radiosensitive than those with effector roles.

Historical perspective

In 1899, Caesar Boeck described a patient with lym-phadenopathy and multiple skin nodules with characteristic epithelioid granulomas on histologic examination he proposed the term 'multiple benign sarkoids' for this condition. The view that sarcoidosis is a multisystem disease was first clearly expressed by Jorgan Schaumann in 1914. Thirty years later, Sven Lofgren observed that sarcoidosis frequently presents with asymptomatic bilateral hilar adenopathy or with erythema nodosum. For many years, sarcoidosis was conceptualized as a disease of suppressed immunity with peripheral lymphopenia and cutaneous anergy. Landmark studies of pulmonary sarcoidosis in the late 1970s led to a fundamental reappraisal of sarcoidosis as a disease of enhanced, cell-mediated immune activity associated with granulomatous inflammation.

Type V hypersensitivity

See also Acute inflammatory reaction Allergens Anaphylatoxins Antiglobulin (Coombs') test Arthus reaction Atopic allergy Autoimmune diseases Blood transfusion reactions Cell-mediated immunity Contact hypersensitivity Delayed-type hypersensitivity Eczema Food allergy Granuloma Hemolytic disease of the newborn Immune complexes Rhinitis, allergic Sarcoidosis.

Background Definition

Sarcoidosis is a systemic, idiopathic disease characterised by the formation of non-caseating epitheliod granulomas that disrupt underlying tissue function.1 While sarcoidosis can affect virtually any organ system, pulmonary (> 90 ), hepatosplenic (50-80 ), haematological (40 ), musculoskeletal (39 ), ocular (30-50 ), cutaneous (25 ), cardiac (5 ) and neurological (5-10 ) manifestations are most common.1 Cutaneous manifestations of sarcoidosis typically present at disease onset, and with the exception of erythema nodosum, do not correlate with the severity of disease. Erythema nodusum tends to be associated with acute, benign, spontaneously resolving sarcoidosis.2 Skin lesions in sarcoidosis can be divided into specific lesions (i.e. skin biopsy demonstrates non-caseating granulomas) and non-specific lesions (i.e. reactive states). Specific lesions include papules, nodules, plaques, subcutaneous nodules, infiltrative scars and lupus pernio. Plaques and papules are the most common...

Aims of treatment

Treatment for cutaneous sarcoidosis is indicated if the skin findings are disfiguring. Available treatment modalities include topical and intralesional steroids, oral steroids, antimalarials and various immunosuppressive agents. Because cutaneous sarcoidosis may spontaneously regress and the available therapeutic modalities have the potential for substantial toxicity, it is important to carefully weigh the risks of treatment against the benefits. However, patients often seek treatment because of the poor cosmesis of cutaneous sarcoidosis, especially on the face, even if it is not disfiguring. The dermatologist therefore needs to be aware of the evidence-based treatment options available for cutaneous sarcoidosis.

Methods of search

We searched the Cochrane Library for sarcoidosis or sarcoid. We searched Medline from 1966 to 2001 using the terms cutaneous sarcoidosis or sarcoidosis and therapeutics or treatment or prednisone or steroids or glucocorticoids or allopurinol or chloroquine or hydroxychloroquine or antimalarial or methotrexate or tretinoin or isotretinoin or tetracyclines or minocycline or phonophoresis or surgery or intralesional or pulse dye laser as subject heading or title or key word.

Oral steroids Benefits

Oral glucocorticoids are postulated to work in systemic sarcoidosis by virtue of their Figure 49.1 Cutaneous sarcoidosis Figure 49.1 Cutaneous sarcoidosis anti-inflammatory and immunosuppressant capabilities. For the same reasons, they are often offered as first-line treatment for lesions of cutaneous sarcoidosis.14,15 However, there is very little evidence to support their use for this indication. Several studies have been conducted to evaluate the efficacy of steroids (particularly long-term steroids) for treatment of pulmonary sarcoidosis. Although some study participants were noted to have skin findings, none of these studies evaluated resolution or improvement of skin lesions as a clinical endpoint.16-23 In 1967, James et a .24 conducted a randomised prospective, placebo-controlled trial in which they compared the efficacy of prednisolone, 20 mg day, with oxyphenbutazone, 400 mg day, and placebo for the treatment of sarcoidosis with multisystem involvement. Seventy-five patients...

Commentimplications for clinical practice

Manifestations of sarcoidosis however, very little objective data exist to support the use of steroids for the cutaneous manifestations of sarcoidosis. In the articles reviewed 56 patients were treated with oral steroids alone, of whom 17 had positive results. In patients with sarcoidosis for whom the main indication for treatment is cutaneous lesions, there is insufficient evidence to conclude that oral steroids are beneficial. Large randomised placebo-controlled therapeutic trials will be necessary for definitive proof. Despite the lack of randomised-controlled data on oral steroids for cutaneous sarcoidosis, many dermatologists use it as first-line therapy. This is based on steroids reversing the manifestations of pulmonary and other extrapulmonary changes of sarcoidosis.4,28-30

Plastic surgery Benefits

There are no systematic reviews or RCTs of the role of plastic surgery in the treatment of cutaneous sarcoidosis however, several case reports were found. In 1970, O'Brien described two patients successfully treated with plastic surgery for lupus pernio.75 In 1984, Shaw etal.76 described a man with a 6-year history of treatment-resistant lupus pernio successfully treated with surgical excision and split skin grafting the result remained good 2-5 years after surgery. Collison et al77 described a man with extensive ulcerative nodules of the lower extremities, which were resistant to topical intralesional steroids, oral steroids, hydroxychloroquine and methotrexate. He was treated with vigorous operative debridement and partial-thickness skin grafting. While the grafts were well accepted (80 ), the patient developed new ulcerating nodules in previously uninvolved skin 2 months after surgery. Stack etal.78 report on a black male with extensive facial lesions who was treated with CO2 laser...

Topical corticosteroids and intralesional injections

While topical corticosteroids and intralesional injections are often recommended as first-line treatment for the cutaneous manifestations of sarcoidosis,12,14,15,30 little evidence is presented regarding their efficacy for this indication. Khatri et al.80 describe a case of lupus pernio which improved with topical 0-05 halobetasol propionate twice daily for 10 weeks. Volden et al.81 describe three cases of cutaneous sarcoidosis that went into remission within 3-5 weeks of treatment with once-weekly clobetasol propionate covered with hydrocolloid dressing. The use of intralesional hydrocortisone and cortisone were reported in 1953 by Sullivan et al. 82 Eighteen skin lesions in five patients with cutaneous sarcoidosis were injected with 2-5 mg doses of hydrocortisone. All lesions developed evidence of regression by 14 days after the injection, with no evidence of recurrence 14 weeks later. Seven skin lesions in four patients were injected with 2-5 mg cortisone. All lesions improved but...

Antimalarials Benefits

Antimalarials such as chloroquine and hydroxychloroquine are 4-aminoquinolones and have been shown to be effective in treating connective tissue diseases. While no randomised placebo-controlled studies exist to evaluate their effectiveness in cutaneous sarcoidosis, a number of open non-randomised non-controlled prospective studies and one comprehensive literature review have been conducted. In 1991, Zic et al.29 published a literature review of studies evaluating the use of antimalarials for treatment of sarcoidosis. They concluded that while corticosteroids should remain first-line treatment for patients with extracutaneous sarcoidosis, chloroquine should be strongly considered in patients for whom the main indication for treatment is disfiguring cutaneous lesions. Zic et al. recommended an initial 14-day course of chloroquine, 500 mg day, followed by long-term therapy with 250 mg day. These conclusions were based on the following studies. of cutaneous sarcoidosis in 1961. The trial...

Granulomatous Disease

SARCOIDOSIS Sarcoidosis is a multisystem granulomatous disease with an uncertain etiology. The lungs, lymph nodes, skin, and eyes are affected most commonly. Skin lesions are common and include classic painless erythematous nodules, erythema nodosum, on the extremities. Oral involvement is primarily limited to enlargement of major and minor salivary glands, and xerostomia is a common complaint. Mucoceles of the minor salivary glands are common, and biopsy of these lesions may result in the diagnosis of sarcoidosis.19

VT related to regions of scar

The majority of sustained monomorphic VTs are caused by re-entry involving a region of ventricular scar. The scar is most commonly caused by an old myocardial infarction, but arrhythmogenic right ventricular dysplasia, sarcoidosis, Chagas' disease, other non-ischaemic cardiomyopathies and surgical ventricular incisions for repair of tetralogy of Fallot, other congenital heart diseases, or ventricular volume reduction surgery (Batista procedure) can also cause scar related re-entry. Dense fibrotic scar creates areas of anatomic conduction block. Secondly, fibrosis between surviving myocyte bundles decreases cell to cell coupling, and distorts the path of propagation causing slow conduction, which promotes re-entry (fig 25.2).5 These re-entry circuits often contain a narrow isthmus of abnormal conduction. Depolarisation of the small mass of tissue in the isthmus is not detectable in the body surface ECG. The QRS complex is caused by propagation of the wavefront from the exit of the...

The immunological role of calcitriol

In contrast to endocrine synthesis of calcitriol in the kidney, normal macrophages have also been shown to synthesize calcitriol when activated by agents such as interferon y and lipopolysaccharide. Production of the hormone may thus act as part of the normal immune response and induction of calcitriol synthesis in response to infection may stimulate the synthesis of other inflammatory mediators such as interleukin 1 (IL-1), which will in turn affect the level of lymphocyte activity. Initial evidence for the interaction of calcitriol with the immune system arose from studies of the disease sarcoidosis, a chronic granulomatous disorder often associated with hypercalcemia and elevated circulating levels of calcitriol. The latter have been attributed to ectopic synthesis of calcitriol by immune cells associated with sarcoidosis, such as alveolar macrophages. The production of the hormone by sarcoid macrophages appears to be insensitive to feedback control by calcitriol itself, as well as...

Entrapment Neuropathies

Several alternative diagnoses should be considered. Stroke can lead to sudden facial weakness that involves only the lower face but also leads to neurologic involvement below the neck or other cranial neuropathies. Lyme disease and GBS can cause facial paralysis, as discussed elsewhere in this chapter. In patients with cancer, facial weakness may herald the metastatic spread of malignancy. The ear should be inspected carefully to rule out ulcerations caused by cranial herpes-zoster activation (Ramsay Hunt syndrome), which should be treated with oral acyclovir. Facial paralysis also can be seen in sarcoidosis, collagen vascular disease, and polio. All patients with facial weakness should be screened for HIV risk factors, since seventh nerve palsy can occur at the time of seroconversion. Lyme disease affects individuals exposed to the tick-born pathogen Borrelia burgdorferi. Although its neurologic manifestations are multiple, one of the most common sites of involvement is the...

Insights gained from animal models of ocular autoimmunity

Figure 1 Histopathology of experimental and clinical uveitis. (A). Section through a healthy mouse eye. Note ordered structure of tissue layers and absence of inflammation. V vitreous body G ganglion cell layer (cell bodies and nuclei) P photoreceptor cell layer (nuclei and outer segments) rpe retinal pigment epithelium c choroid s sclera, b retinal blood vessel. (B). Section through a mouse eye with experimental autoimmune uveitis induced with IRBP. Note disrupted ocular architecture cells and debris in the vitreous, vasculitis, retinal folds and retinal detachment, subretinal hemorrhage, subretinal granuloma, disrupted retinal pigment epithelium, infiltrated and thickened choroid. (C). Section through a human eye with uveitic disease. This patient has ocular sarcoid. Note similarity in histological appearance to experimental uveitis in the mouse. Figure 1 Histopathology of experimental and clinical uveitis. (A). Section through a healthy mouse eye. Note ordered structure of tissue...

TABLE 236 Clinical Manifestations of Hypernatremic States Related to Serum Osmolality

DIABETES INSIPIDUS A particularly interesting cause of hypernatremia is diabetes insipidus (DI), which results in excessive loss of hypotonic urine. Diabetes insipidus may be central in origin (due to a failure of secretion of ADH) or nephrogenic (due to renal unresponsiveness to ADH). About 30 percent of central DI is idiopathic and about 70 percent is secondary to neoplasms (25 percent), pituitary surgery (20 percent), or trauma (15 percent). Most of the remaining 10 percent is due to various granulomas (tuberculosis, sarcoidosis, or eosinophilic granuloma) or local vascular problems (aneurysms, thrombosis, or Sheehan syndrome). Nephrogenic DI may be primary (familial) or secondary to a wide variety of causes, including hypercalcemia, hypokalemia, renal disorders, various drugs (including lithium, demeclocycline, amphotericin B, aminoglycosides, and cisplatin), hematologic disorders (sickle cell disease and myeloma), malnutrition, or amyloidosis.

Granuloma

The germ granuloma was introduced by Virchow in 1865 to describe certain well-circumscribed swellings consisting of what he thought was granulation tissue, found in a number of chronic infectious diseases including tuberculosis, leprosy, syphilis and leishmaniasis. Later authors, including Cohnbeim in 1877, distinguished large, swollen, epithelial-like cells. These they called epithelioid cells and differentiated them from the lymphoid elements in these lesions. In 1893, Metchnikoff formally recognized that these cells were related to the cells he had newly described as macrophages. The relation between granulomatous diseases and delayed-type hypersensitivity was recognized by Zinsser in 1925. Cells of the mononuclear phagocyte series are now considered to be the most important feature of granulomas. Although granuloma formation is generally a tissue response to particulate or fixed material in the tissues, they are not necessarily associated with infectious diseases or with delayed...

Pathology

The histologic hallmark of sarcoidosis is the presence of discrete, noncaseating, epithelioid cell granulomas typically at different stages of development (Table 1, Figure 1). The dominant cell in the central core is the epithelioid cell, thought to be a differentiated form of a mononuclear phagocyte. CD4' lymphocytes and mature macrophages are typically interspersed throughout the epithelioid core, whereas both CD4 and CD8 lymphocytes are seen in the periphery of the granuloma. Approximately 5-10 of T cells at sites of inflammation are IL-2R' and 20-50 are HLA-DR+, indicative of their recent activation. Figure 1 Principal events involved in granuloma formation in sarcoidosis. (A) In response to an unknown stimulus, activated macrophages and oligoclonal CD4 T cells accumulate at sites of inflammation. (B) Epithelioid cells and giant cells, derived from differentiated macrophages, aggregate with fibroblasts, other CD4 and CD8 T cells and mononuclear phagocytes to form granulomas. These...

Immunopathogenesis

The pathologic features of sarcoidosis are typical for 'immune-mediated' granulomatous diseases of known etiology such as mycobacterial or fungal infections and chronic beryllium disease. In these disorders, granulomatous inflammation is regulated by a complex interplay among T cells, mononuclear phagocytes, fibroblasts, dendritic cells and other accessory cells. In sarcoidosis, this inflammatory process results in pathologic changes in organ function by disrupting normal architecture, damaging local tissues and producing cytokines and chemical mediators with local and systemic effects. Current information on the immunopathogenesis of sarcoidosis has been derived in large part from studies of lung cells and fluid from the lower respiratory tract obtained by bronchoalveolar lavage.

Sjogrens Syndrome

Clinical descriptions of patients with dry eyes and a dry mouth associated with swellings of lacrimal and salivary glands began to appear in the medical literature towards the end of the nineteenth century. In all probability a heterogeneous group of disorders such as sarcoidosis and lymphoma was included in these early descriptions, but in 1888 Mikulicz gave a histo-

Myocarditis

Myocarditis is the term used to indicate acute infective, toxic or autoimmune inflammation of the heart. Reversible toxic myocarditis occurs in diphtheria and sometimes in infective endocarditis when autoimmune mechanisms may also contribute. Persistent viral infection of the myocardium was first demonstrated a decade ago.1 Slow growing organisms such as chlamydia and trypanosomal infection in Chagas' disease are causes of chronic myocarditis. Non-infective causes in sarcoidosis and the collagen vascular diseases need to be sought.

Allopurinol

Allopurinol is a xanthine oxidase inhibitor used in the treatment of gout and some inflammatory diseases. Its anti-inflammatory capabilities are the basis for its use in cutaneous sarcoidosis. No systematic reviews or RCTs describing the use of allopurinol for treatment of cutaneous sarcoidosis were found. One non-randomised non-controlled open prospective study of six patients with cutaneous sarcoidosis reported treatment with allopurinol, 100 mg day, Additional information was found in several case reports. Pfau et al.55 treated two patients with scar sarcoidosis and two patients with nodular sarcoidosis with allopurinol 300 mg day over a 3-7-month period. Lesions completely resolved in the patients with scar sarcoidosis and partially resolved in the patients with nodular sarcoidosis. Rosof et al.56 observed remission of cutaneous sarcoidosis in two patients treated with allopurinol. Pollock57 reported on two patients with cutaneous sarcoidosis one treated with allopurinol, 100 mg...