Natural Scleroderma Relief
In PSS, kidney involvement occurs in approximately 60 to 70 . Scleroderma renal crisis, manifest by malignant hypertension, acute renal failure, some even with infarcts, develops in approximately 20 of patients with PSS (21). Age at onset of systemic sclerosis is 30 to 50 years, and females are affected more than males.
Blood vessels, is a pathologic hallmark of this disease. The underlying pathogenesis of scleroderma is a widespread disorder of microvasculature which results in extensive, proliferative fibrosis. Microvascular lesions in arterioles and capillaries generally precede fibrosis and proliferative changes in vital organs such as the lungs, heart, gastrointestinal tract and kidneys. Although the exact immunopathogenesis is poorly understood, this is an immunologically mediated disease for example, autoantibodies abound in scleroderma. Several of these autoantibodies are listed in Table 1. T cell abnormalities have also been described in scleroderma, suggesting a role for both TH1 and TH2 cells. In particular, TH1 cell responses are present and there is an increased expression in serum of both interleukin 2 (IL-2) and IL-2 receptors and endothelial cell growth-inhibition factor (a TH1 granzyme). Data also exist to suggest activation of T cells by collagen. This suggests a scenario whereby...
In involvement of the small bowel by scleroderma, muscle atrophy results in atonicity and dilatation. Replacement of the atrophied muscle by collagen occurs in a patchy fashion, with perivascular accumulation in the submucosa. Accordion-pleating of the mucosal folds occurs in the face of luminal dilatation, resulting in a typical hidebound appearance.11 The individual folds are not thickened. At sites without sclerosis, areas of more normal or atrophic bowel may bulge out between the tethered sections, producing sacculations or pseudodi-verticula13 (Fig. 14-24). In distinction to true divertic-ula, these are wide-mouthed and occur on the anti-mesenteric border. Sacculations are typical of scleroderma, though more commonly seen in the colon than in the small bowel.
Collagen vascular diseases are a group of disorders that includes systemic lupus erythematosus and systemic sclerosis or scleroderma. They are immunologically mediated. Nearly a quarter of systemic lupus patients develop oral lesion affecting the palate, buccal mucosa, or gingiva. These lesions may be lichenoid in
The pseudosacculations of the haustral row opposite to that primarily involved by fixation are basically a functional phenomenon. They are largely a consequence of disordered peristaltic contractions and thus change in size, shape, and axis. In contrast, the pseudosacculations of scleroderma of the colon are constant structures brought about by atrophy of the muscle and collagenous replacement. Characteristically, they have wide mouths, contain fecaliths, and fail to contract on postevacuation studies. They are most consistently seen arising from the TO-TL haustra of the transverse colon (Fig. 15-22). Fig. 15-22. Scleroderma of the colon. Fig. 15-22. Scleroderma of the colon.
The skin suffers toxic effects itself, including cancer, primary irritation, allergic reactions, hair loss, pigment disturbances, ulceration, and chloracne. Dermatitis is an inflammation of the dermis. Irritant contact dermatitis and allergic dermatitis can both be caused by exposure to chemicals and produce similar symptoms, including hives, rashes, blistering, eczema, or skin thickening. The difference between them is that a true allergy takes time to develop, typically at least two weeks whereas irritation does not require a previous exposure. For example, no one reacts to poison ivy when first exposed. Only after a second or subsequent exposure does the itchy rash develop.
By diminishing sweating ability, many skin diseases can decrease the ability to disperse heat. Scleroderma, cystic fibrosis, eczema, psoriasis, and burns decrease sweating ability. Congenital diseases, such as ectodermal dysplasia, involving the sweat glands increase risk of heat injury. Interestingly, even the presence of simple heat rash has been shown to decrease sweating. Histologic studies of skin with heat rash have demonstrated obstruction of sweat gland ducts by keratin debris, resulting in significantly lower sweating rates and decreased tolerance time in a hot environment. 13
Finally, even within a species there is diversity in the acute phase response to different stimuli, to different disease processes and between different individuals. This has been most extensively studied in the case of CRP and SAA responses in humans, in whom there is a small number of serious inflammatory or tissue-damaging disorders characterized by absent or minimal acute phase production of these proteins. These exceptional disorders include systemic lupus erythematosus, dermatomyositis, Sjogren's disease, scleroderma, ulcerative colitis and leukemia, in all of which only a minority of patients have more than modest elevations of CRP or SAA concentration.
Organs inversely correlates with the autoimmune response. They were not affected in a similar way in the nonresponding LEW rats. All manifestations of mercuric chloride-induced nephritis in BN rats could be prevented by treatment with cyclosporine. Mercury also induces the formation of immune complexes which cause a mesangial immune complex glomerulonephritis and immune complex deposition in the vessel walls of the spleen and liver. In H2S strains of mice (such as A.SW and SJL) mercury causes formation of autoantibodies against the highly conserved nucleolar protein fibrillarin. Interestingly, autoantibodies against this antigen are found in patients with scleroderma.
Association with scleroderma and the sicca complex. The autoantibodies found in PBC include antibodies to thyroid antigens, nuclear antigens, thymocyto-toxic autoantibodies, and mitochondrial-specific antibodies. scleroderma sera. In systemic lupus erythematosus (SLE) sera, autoantibodies specific for Sm and Ul-RNP, which are both components of small nuclear ribonucleoproteins (snRNP), inhibit splicing of early RNA sequences, and autoantibodies to proliferating cell nuclear antigen (PCNA) inhibit DNA replication. Additionally, autoantibodies to the La (SS-B) nucleo-protein antigen, present in primary Sjogren syndrome, interfere with the transcription of small RNA molecules. The significance of these findings in terms of disease expression has yet to be determined, but two schemes are prominent. First, as for the mitochondrial antigens of PBC, many of the described autoantigens are intracellular enzymes and exist not as single proteins but as components of large complexes, and, second,...
Rarely, diabetes mellitus results from a decreased biological response to a normal amount of insulin. In type A insulin resistance, the problem lies in the insulin receptor, which is quantitatively or qualitatively abnormal, but in the type B syndrome autoantibodies to the insulin receptor produce diabetes mellitus. In vitro, using short-term culture experiments, these antibodies mimic the action of insulin, which may account for the occurrence of hypoglycemia in some patients. More typically, however, there is massive insulin resistance, so that even 15 000 units of insulin per day may not lower blood glucose, and prolonged in vitro experiments reveal the antagonistic properties of the antibodies. About one-third of these patients have other autoimmune diseases, including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, primary biliary cirrhosis,
Intestinal pseudo-obstruction encompasses several intestinal motor disorders characterized by episodes that suggest intestinal obstruction because defecation stops and abdominal distension, pain, and vomiting occur, but in which no mechanical obstruction is found. It may be due to primary abnormalities of the visceral muscle or nerves or be secondary to chronic renal failure, hypothyroidism, diabetes mellitus, amyloidosis, scleroderma, or muscular dystrophy. There is no effective treatment that is specific for intestinal pseudo-obstruction. If the patient has bacterial overgrowth, this should be treated with antibiotics. If nutrition is impaired, administration of liquid, low-residue feeds enterally is required rarely, parenteral (intravenous) feeding is necessary.
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.
Some organisations, like the Raynaud's and Scleroderma Association, are beginning to suggest areas of research, based on their members' experience. For example, the association decided to offer funding for a project on calcinosis - a big problem for many people with the disease. This is not a particularly attractive topic and can be difficult to tackle. After several months waiting for a worthwhile proposal, a project was started in 2002. The association is also keen to fund a project to investigate the causes of childhood scleroderma. It is also worth noting that the UK National Eczema Society supported and funded the double-blind controlled study conducted at Liverpool University of the effect of housedust mites in adults and children with eczema.7 Other organisations, such as the National Eczema Association for Science and Education based in the USA, have set up and supported international research meetings.
Grossly, petechial hemorrhages or even renal infarcts may be present in patients with scleroderma renal crisis, similar to hemolytic uremic syndrome or malignant hypertension. Microscopically, there is fibrinoid necrosis of afferent arterioles. Interlobular arteries show intimal thickening, proliferation of endothelial cells, and edema. Red blood cell fragments are often present within the injured vessel wall, and there may be vessel wall necrosis and or fibrin thrombi within vessels. Glomeruli may show isch-emic collapse, or fibrinoid necrosis. In chronic injury, arterioles show reduplication of the elastic internal lamina, so-called onion skin pattern (Fig. 10.4). Tubules may show degeneration and even necrosis, especially in scleroderma crisis. Tubulointerstitial fibrosis develops with chronic injury (19,20).
The glomerular features are not specific for chronic graft rejection, but are typical. The most distinctive features in my opinion are the loss of endo-thelial fenestrations and duplication of the GBM. The other diseases with similar light and electron microscopic glomerular features also are characterized by endothelial injury (thrombotic microangiopathy, scleroderma, eclampsia). If immune complex deposits are more than occasionally found, or if in a subepithelial location, recurrent or de novo glomerulonephritis should be suspected. The features that favor chronic rejection over chronic CsA toxicity are duplication of the GBM and marked intimal fibrosis of the small arteries. Atypical, monomorphic infiltrates particularly with necrosis, are highly suspicious of post-transplant lymphoproliferative disease (PTLD). Peripheral hyalinosis replacing smooth muscle cells in the arterioles favors CsA toxicity.
This refers to propulsive contractions that are triggered by local stimuli within the esophagus and are transmitted by normal peristaltic activity. They may be initiated by a large food bolus, reflux, or by endoscopy. Physiologically, secondary peristalsis is one of the clearance mechanisms of the esophagus. Absence of this activity may signify a motility disorder (achalasia, scleroderma).
HEMOLYSIS IN VASCULITIS MAHA can be seen in vascular diseases such as SLE, polyarteritis nodosa, Wegener's granulomatosis, and scleroderma. In this setting, damage to the endothelial surface is thought to result from deposition of immune complexes and fibrin in the microcirculation.
With very few exceptions, the inbred strains are based on the White Leghorn type of domestic chicken. Attempts to inbreed other types of chicken or species of bird (ducks, Japanese quail) have been made, but have not generally been successful. There are lines of chickens with hypogammaglobulinemia resulting from abnormal bursal development, a line in which a disease similar to systemic scleroderma can be induced, and 'obese' chicken strains which develop a spontaneous autoimmune thyroiditis similar to Hashimoto's disease. Transgenic chickens can be produced by DNA transfer into fertilized eggs viral vectors which can give high levels of somatic transgenesis are available. A chicken genome mapping project is under way.
The pathogenesis of PSS is probably immune with unknown inciting events. Autoantibodies are often present, including anti-topoisomerase I, anticen-tromere, and anti-RNA polymerase, each present in 25 . Only one of these markers may be positive in any one patient. Some studies have demonstrated cytotoxic antiendothelial factors in serum from PSS patients. Imbalance of vasodilators (e.g., nitric oxide, vasodilatory neuropeptides such as calcitonin gene-related peptide, substance P) and vasoconstrictors (e.g., endothelin-1, serotonin, thromboxane A2) has been described in scleroderma patients. Prolonged vasoconstriction could contribute to structural changes and fibrosis in the kidney as well. Endothelial injury is thought to play a key role in renal PSS, but whether it is primary or initiated by immune injury has not been elucidated. A defect in circulating endothelial progenitor cells in PSS patients has been proposed to underlie deficiency of vasculogenesis and repair in response to...
Most commercially available AM bulk inoculum is a mixture of spores, colonized roots, hyphae, and the substrate on which pot cultures were grown. For EM fungi, many inoculation programs have successfully used the EM vegetative mycelium. The production of mycelial inoculum for large-scale inoculation programs is often costly and pure culture isolates can be difficult to maintain (Marx and Kenney 1982). In contrast, EM sporocarps contain a significant amount of spores that can be collected from the fruiting populations and easily dried and stored until application. Spores from EM fruiting bodies of Pisolithus, Scleroderma, and Rhizopogon are most frequently used as inoculum. Spores of Laccaria, Descolea, Scleroderma and Pisolithus spp. have recently been proposed as candidates for nursery inoculation programs for eucalypti (Lu et al. 1998) and Rhizopogon spp. are commonly used to inoculate Doulgas-fir seedlings in commercial nurseries (Castellano 1994).
Light and electron microscopic glomerular features also are characterized by endothelial injury (thrombotic microangiopathy, scleroderma, and eclampsia). A chronic lesion in the peritubular capillaries has been observed consisting of splitting and multilayered duplication of the basement membrane, analogous to and correlated with the chronic glomerular changes (57). Thus, the common theme in chronic rejection is endothelial damage at the level of the arteries, glomeruli, and peritubular capillaries.
Increased expression of hsp70s has been observed in autoimmune diseases such as scleroderma and systemic lupus erythematosus (SLE), but it is not clear whether this is a contributory factor or a consequence of disease. However, exposure of kera-tinocytes to ultraviolet light results in accumulation of HSP70 in the nucleoli and a concomitant increase in binding sites for autoantibodies to nuclear antigens which are a feature of erythematosus lesions. Some allelic variation has been found in the MHC-linked hsp70 genes, but numerous studies have failed to show a direct contribution of any of the variants to a particular autoimmune disease. Complete deficiency of C4 is rare and is correlated with severe immune complex disease, whereas partial deficiency of C4 is more common and is thought to be associated with an increased susceptibility to SLE, scleroderma and primary biliary cirrhosis. Deficiency of P450c21B is the most frequent cause (95 ) of congenital adrenal hyperplasia (CAH), which...
Severe viral infections are usually associated with a significant acute phase response but localized viral infections are generally a much less potent stimulus for CRP production than bacterial infections. In addition there are some important disorders in which CRP levels are usually normal or only modestly increased, even in the presence of severe, active, tissue-damaging pathology. These include systemic lupus erythematosus (SLE), ulcerative colitis, derma-tomyositis, scleroderma, Sjogren's syndrome and leukemia. However, in all of them, intercurrent microbial, and especially bacterial, infection always stimulates a major acute phase response. The mechanisms underlying these phenomena are not known. Studies of SLE-like autoimmune disease in inbred mouse strains suggest that the acute phase response to this type of autologous tissue damage may be genetically determined, but the locus of gene action, whether at the level of mediators, receptors, acute phase protein synthesis or...
Gastric stasis refers to the delayed emptying of gastric contents and this results in patients experiencing early satiety, bloating, nausea, and vomiting. Endo-scopy can confirm the presence of gastric stasis by finding retained food after an overnight fast. Systemic disorders such as scleroderma and diabetes mellitus can have neuromuscular effects that can affect the stomach. Neurological disorders can likewise cause gut dysmotility.
Currently, the recommended follow-up for local recurrence is involves routine clinical examination and mammography at least every 2 years. Ultrasonography and core biopsy are used to confirm the diagnosis of recurrence. In the first 6 months after surgery, mammograms show a general increased density, architectural distortion, skin thickening, asymmetric densities, dystrophic calcification and features of fat necrosis (Sickles and Herzog 1981 Paulus 1984 Krishnamurthy et al. 1999). Mam-mographic changes are most helpful in suggesting recurrence 6 months to 1 year later after surgery. It is well recognised that features of scar tissue can mimic those of recurrent cancer on mammography (Stomper et al. 1987) and, therefore, any increase in the extent of the post-surgical abnormality or the development of a mass within the area of distortion must be regarded as suspicious. The overall positive predictive value of cancer detection in the treated breast using mammography is thought to be...
Most systemic rheumatic diseases may affect kidney function. Glomerulonephritis is a major determinant of morbidity in patients with lupus and Wegener's granulomatosis. Urinalysis abnormalities (hematuria, proteinuria) and hypertension are apparent before serum creatinine rises. Patients with lupus and nephrotic syndrome can develop renal vein thrombosis due to urinary loss of antithrombin III they present with flank pain and proteinuria. In diffuse scleroderma, renal dysfunction secondary to hypertension and microangiopathy typically develops rapidly over days to a few weeks.