Severity Of Vasculitis Research Articles

Assessment of the correlation of commonly used laboratory tests with clinical activity, renal involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies

BackgroundThe aim of the study was to assess the correlation of commonly used laboratory tests with clinical activity, degree of kidney involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies.MethodsThe study included 28 patients with active AAV (BVAS ≥ 3). The following tests were performed: MPO-ANCA, PR3-ANCA, peripheral blood count, ESR, CRP, procalcitonin, creatinine, GFR, urea, albumin, fibrinogen, d-dimer, components of the C3 and C4 complement systems, urinalysis with sediment evaluation and diurnal proteinuria. The assessments were conducted twice: at study entry (A0) and after 6 months (A6) (BVAS = 0).ResultsAt the time of inclusion in the study, the mean creatinine concentration was 3.39 mg/dl (GFR 33.17 ml/min/1.73 m²), after achieving remission in 11 patients (39.3 %) GFR remained below 30 ml/min/1.73 m², 4 patients (14.3 %) continued renal replacement therapy, and 3 patients (10.7 %) with advanced renal failure died. Microscopic hematuria occurred in 80.9 % of the studied population, withdrew in most patients, strongly correlated with renal involvement p < 0.001 and was not related to disease severity p = 0.147. CRP, ESR, fibrinogen, d-dimer, albumin and hemoglobin in the peripheral blood showed a strong correlation with the clinical activity of AAV and well identified severe patients. High procalcitonin concentrations correlated with a severe form of the disease, pulmonary involvement with respiratory failure and alveolar hemorrhage (mean 3.41 ng/ml, median 0.91 ng/ml, SD 7.62, p = 0.000), and were associated with the occurrence of infectious complications and the need to administer antibiotic therapy. ANCA antibodies were useful in the evaluation of patients with AAV, the amount of antibodies did not correlate with the severity of vasculitis (p = 0.685) and the results in many patients did not match the expected assumptions.ConclusionsCRP, ESR, fibrinogen, d-dimers, albumin and hemoglobin in the peripheral blood correlate well with the activity of vasculitis and identify severe patients. The resolution of microscopic hematuria suggests remission of the disease in the renal area. Procalcitonin may be slightly increased in patients with active AAV without infection, high concentrations are strongly associated with infectious complications. ANCA antibodies should always be interpreted in the context of the observed clinical symptoms.

Anti-tubercular therapy alone for treatment of isolated tubercular retinal vasculitis.

To compare the time to resolution of perivascular infiltrates in tubercular retinal vasculitis (TRV) between anti-tubercular therapy (ATT) alone, and in combination with systemic corticosteroids. Observational retrospective cohort study in a tertiary eye centre in eastern India. Patients with TRV who were treated with anti-tubercular therapy (ATT) alone (Group A), or in combination with systemic corticosteroids (Group B) were included in the study. Eyes with additional inflammatory signs (cystoid macular oedema, vitritis ≥2+, optic disc oedema) were excluded. Resolution was defined as complete disappearance of perivascular infiltrates on seven-field fundus photographs. Descriptive statistics were used for demographic data. A linear mixed effects model was applied to adjust for intereye correlations, in patients with bilateral disease. The primary outcome measure was time to resolution of perivascular infiltrates. Secondary outcome measure was need for laser or surgical intervention for management of complications of TRV. Fifty eyes of 39 patients (Group A 21/18 and Group B 29/21) were included. Both groups had similar demographics and severity of vasculitis. All patients had complete resolution of TRV. On adjusting for intereye correlation, the mean difference in time to resolution between the two groups (Group A, 3.24 [95% CI 2.69-3.77] months, and Group B, 4.76 [95% CI 3.52-5.99] months) was not statistically significant (0.96 weeks [-0.52 to 2.45] p = 0.21). Vaso-occlusive complications and healing patterns were similar in both groups. ATT alone, may be sufficient for resolution of perivascular infiltrates, in TRV without additional inflammatory signs.

HCV related severe cryoglobulinemic vasculitis treated with plasma exchange and rituximab: case report and literature review.

Mixed cryoglobulinemia is the most prevalent extrahepatic manifestation of chronic HCV infection. It is usually a benign lymphoproliferative disorder which presents as vasculitis affecting different organs. Although life-threatening cryoglobulinemic vasculitis (CryoVas) is rare, it is sometimes the first and possibly lethal complication. Its treatment depends on the severity of vasculitis and can be challenging. High dose of corticosteroids, immunosuppressive agents and plasma exchange represent the first-line treatment, which should be followed by antiviral therapy. Rituximab is an effective and safe treatment option. However, the data about its use in life-threatening conditions are scarce. We report the case of a patient with severe, relapsing and life-threatening HCV-related CryoVas resistant to standard therapy who had had an initial beneficial response to rituximab added to plasma exchange that was later compromised by the development of sepsis. We also review the literature and discuss manifestations and therapy of life-threatening Cryovas with focus on rituximab use.

Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection.

Progressive Coronary Dilatation Predicts Worse Outcome in Kawasaki Disease

To explore the implication of serial coronary changes on the late coronary outcomes in patients with Kawasaki disease (KD) with coronary aneurysms ≧ 4 mm. We performed a retrospective review of 78 patients with KD with large coronary aneurysms (1980-2013, male: 76.9%; 792 patient-years). Progressive coronary dilatation was defined for those with progressive enlargement of coronary arteries in 3 consecutive echocardiograms. We studied 27 patients with KD with giant aneurysms (≧ 8 mm) and 51 patients with KD with medium aneurysms (4-8 mm). All the giant and 43.1% of medium aneurysms persisted during the study period. For the patients with giant aneurysms, their 10-year freedom from acute myocardial infarction/cardiovascular death and all ischemia was 66% and 52%, respectively. The median intervals for the aneurysm diameters reaching their peak were 3.3 months (giant) and 0.25 months (medium), respectively. In patients with giant aneurysms, the 10-year freedom from ischemia was much lower in those with progressive coronary dilatation (28% vs 59%, P = .021). In patients with medium aneurysms, the probability of 5-year persistence of aneurysm was much greater (67.2% vs 14.8%, P < 10(-3)) in those with progressive coronary dilatation. Male sex and intravenous immunoglobulin therapy were not associated with the late outcomes in the patients with KD who had aneurysms larger than 4 mm. In addition to coronary diameters 1 month after the onset of KD, progressive coronary dilatation at 2 or more months after diagnosis may be an indicator of duration, and the severity of vasculitis and adverse dilative remodeling were associated with worse late coronary outcomes.

Systemic Vasculitis in Various Organs of 33 Rheumatoid Arthritis and 11 Progressive Systemic Sclerosis Patients – A Comparative Postmortem Study

Objective: The aim of this study was (1) to compare the prevalence and severity of Systemic Vasculitis (SV) in various organs of Rheumatoid Arthritis (RA) and of progressive Systemic Sclerosis (SSc) patients, (2) To determine the complications and lethal outcome caused by vasculitis in RA and SSc. Patients and Methods: Twelve organs (heart, lung, liver, spleen, kidneys, pancreas, gastrointestinal tract, adrenal glands, skeletal muscle, peripheral nerve, skin and brain) of 33 RA and of 11 SSc with SV were studied microscopically. RA and SSc were confirmed clinically according to the criteria of the American College of Rheumatology. The basic disease, the complications, and the lethal outcome caused by vasculitis were determined and analyzed retrospectively, reviewing the clinical and pathological reports, tissue samples, and the histological slides. The existence (prevalence) of vasculitis in various organs was determined based on the presence of vasculitis in blood vessels of different calibers. The severity of vasculitis in various organs was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale (based on the number of involved vessels/light microscopic field x40). Results and Conclusions: SV was observed in all of 33 RA and 11 SSc patients with variable prevalence and severity. The average value of prevalence and severity/organ in SSc was appreciably higher than that of RA. In RA patients, not all investigated organs were involved with SV and the existence of blood vessels with vasculitis in each organ was different. In SSc patients SV was present in each of the investigated organs, but with different severity. In RA the heart, skeletal muscle, pancreas, lung, kidneys and gastrointestinal tract were most markedly involved, while in SSc the kidneys, spleen, lung, pancreas, heart and gastrointestinal tract were. The high prevalence of SV and the consecutive fibrosis in these organs identify the main targets of autoimmune processes in RA and SSc prior to the more visible skin involvement. The most markedly involved organs denote a favorable site for histological diagnosis of SV, for example skeletal muscle with peripheral nerve (sural nerve) or gastrointestinal tract in RA and the gastrointestinal tract in SSc. The course of the disease, more precisely mortality due to SV,

Role of ultra-widefield fluorescein angiography in the management of uveitis

ObjectiveTo discuss and illustrate the role of ultra-widefield fluorescein angiography (UWFFA) in the diagnosis and management of peripheral retinal vasculitis. DesignRetrospective case series. ParticipantsFour consecutive patients in whom UWFFA showed far peripheral vasculitis were included. All patients were seen between May 2011 and May 2012 at the Doheny Eye Institute. MethodsConventional fluorescein angiogram (FA) images or areas determined by the Early Treatment of Diabetic Retinopathy Study Group protocol for imaging the posterior pole and peripheral retina were superimposed on the UWFFA images. The ability to detect the extent and severity of vasculitis and vascular occlusion using both conventional FA and UWFFA was compared by 2 investigators, and any discrepancies were adjudicated by a third investigator. ResultsIn none of the cases was the full extent of vasculitis and capillary occlusion visible in the fields normally portrayed by conventional FA. In contrast, capillary nonperfusion and peripheral vasculitis were detectable by UWFFA in all cases. In 2 cases, the posterior extent of vasculitis could have been detected by conventional FA. ConclusionsDetection and depiction of the extent and severity of peripheral vascular changes are enhanced with UWFFA, aiding in the management of vasculitis in the retinal periphery.

AB0240 Prevalence and severity of systemic vasculitis in various organs of patients with progressive system

ObjectivesThe aim of this study was to determine: the prevalence and severity of systemic vasculitis (SV) with or without fibromuscular and/or intimal proliferation (FIP) in various organs of SSc patients.Methods12...

AB0466 Prevalence of systemic vasculitis in various organs – a comparative postmortem study of 36 rheumatoid arthritis and 11 progessive systemic sclerosis patients

ObjectivesThe aim of this study was to compare the incidence and severity of systemic vasculitis (SV) in various organs of rheumatoid arthritis (RA) and progressive systemic sclerosis (SSc) patients.MethodsTwelve organs...

AB0467 Cerebral arteritis and vasculogenic recurrent brain necrosis in rheumatoid arthritis

BackgroundVasculitis of the cerebral arterioles and small arteries can lead to local ischaemia and to regressive changes in the brain. This process is more or less widespread and multifocal, depending...

Lymphopenia and Treatment-Related Infectious Complications in ANCA-Associated Vasculitis

ANCA-associated vasculitis (AAV) is treated with potent immunosuppressive regimens. This study sought to determine risk factors associated with infections during first-intention therapy. This retrospective study involved two separate cohorts of consecutive cases of AAV seen from 2004 to 2011 at two university hospitals. The following were assessed: vasculitis severity; therapy; and periods with no, moderate (lymphocyte count, 0.3-1.0× 10(9)/L), or severe (lymphocyte count ≤ 0.3×10(9)/L) lymphopenia and neutropenia (neutrophil count ≤ 1.5×10(9)/L). One hundred patients had a mean age of 57±15 years and a Birmingham vasculitis activity score of 7.7±3.6. Therapy consisted of pulse methylprednisolone (59%), cyclophosphamide (85%), methotrexate (6%), and plasmapheresis (25%) in addition to oral corticosteroids. During follow-up, 53% of patients experienced infection and 28% were hospitalized for infection (severe infection). Only 18% experienced neutropenia, but 72% and 36% presented moderate and severe lymphopenia for a total duration of <0.1%, 73%, and 8% of the treatment follow-up, respectively. Lower initial estimated GFR, longer duration of corticosteroid use, and presence of lymphopenia were risk factors of infections. The rate was 2.23 events/person-year in the presence of severe lymphopenia compared with 0.41 and 0.19 during periods with moderate or no lymphopenia (P<0.001). Similarly, the rate of severe infections was 1.00 event/person-year with severe lymphopenia and 0.08 and 0.10 with moderate and no lymphopenia (P<0.001). This association remained independent of other risk factors. Lymphopenia is frequent during the treatment of AAV, and its severity is associated with the risk of infectious complications.

Prognostic factors in patients with hepatitis C virus infection and systemic vasculitis

Hepatitis C virus (HCV)-related systemic vasculitis can cause significant morbidity and mortality. Most studies of the prognosis of patients with HCV-related systemic vasculitis are based on heterogeneous studies performed before the era of antiviral therapy. The aim of this study was to analyze the clinical, biologic, and therapeutic factors associated with prognosis in a homogeneous series of patients with HCV-related systemic vasculitis who were followed up during the era of antiviral therapy. One hundred fifty-one consecutive HCV RNA-positive patients with vasculitis were prospectively followed up between 1993 and 2009 and were analyzed for clinical, biologic, and therapeutic factors associated with survival. After a median followup period of 54 months, 32 patients (21%) had died, mainly of infection and end-stage liver disease. The 1-year, 3-year, 5-year, and 10-year survival rates were 96%, 86%, 75%, and 63%, respectively. Baseline factors associated with a poor prognosis were the presence of severe liver fibrosis (hazard ratio [HR] 5.31), central nervous system involvement (HR 2.74), kidney involvement (HR 1.91), and heart involvement (HR 4.2). The Five-Factors Score (FFS), a vasculitis scoring system, was significantly associated with outcome. In multivariate analysis, severe fibrosis (HR 10.8) and the FFS (HR 2.49) were significantly associated with a poor prognosis. Treatment with the combination of PEGylated interferon plus ribavirin was associated with a good prognosis (HR 0.34), whereas treatment with immunosuppressive agents was associated with a poor outcome, after adjustment for the severity of vasculitis (HR 4.05). Among patients without severe fibrosis, the FFS was a good predictor of outcome, while among those with severe fibrosis, the severity of vasculitis had no prognostic value. At the time of the diagnosis of HCV-related systemic vasculitis, severe liver fibrosis and the severity of vasculitis were the main prognostic factors. Use of antiviral agents was associated with a good prognosis, whereas treatment with immunosuppressant agents had a negative impact.

Spatial Distribution of Nerve Fiber Pathology and Vasculitis in Microscopic Polyangiitis-Associated Neuropathy

We analyzed the 3-dimensional distribution of pathologic findings in 8 autopsied cases of neuropathy associated with microscopic polyangiitis. Necrotizing vasculitis was commonly and diffusely present in the epineurium of the sciatic/tibial and median nerves. Although findings of vasculitis were distributed diffusely in proximal to distal segments of the nerve trunks, marked loss of myelinated fibers occurred only from the middle to distal segments of these nerves. Neurons of the sensory and sympathetic ganglia were well preserved, as were myelinated fibers of the anterior and posterior spinal roots. Central fascicular nerve fiber degeneration, suggesting direct ischemic damage, occurred in restricted segments of the proximal-middle portion of the sciatic/tibial and median nerve trunks. Vasculitis was also seen in various visceral organs in all patients, but its distribution differed among individual patients; the severity of vasculitis in the other organs did not correlate with that in the peripheral nerves. The distinct spatial distribution pattern of nerve fiber degeneration, in contrast to the ubiquitous presence of vasculitis, suggested that the ischemic zone that directly damages nerve fibers is present in the proximal-middle portion of peripheral nerve trunks in microscopic polyangiitis.

Analysis of pulmonary allergic vasculitis with eosinophil infiltration in asthma model of mice

ABSTRACTHere the authors report pulmonary allergic vasculitis with eosinophil infiltration in an asthma model of mice and investigated its pathogenesis. C57BL/6 and BALB/c mice were sensitized with ovalbumin (OVA). After the inhalation of OVA, the authors measured the cell number and cytokine concentration in the blood and bronchoalveolar lavage fluid (BALF). The authors also examined the histological changes of the pulmonary. The number of eosinophils increased in the blood and BALF in both strains; however, the number in C57BL/6 in BALF was significantly higher than that in BALB/c. Histological analysis demonstrated severe vasculitis of the pulmonary arteries with derangement of the muscle layer and smooth muscle cell hyperplasia in C57BL/6. Semiquantitative analysis of the severity of vasculitis in the pulmonary arteries revealed that the internal vascular space was highly reduced by smooth muscle hyperplasia in C57BL/6 compared to BALB/c mice. The concentrations of interleukin (IL)-4, IL-5, and interferon (IFN)-γ in BALF of C57BL/6 were significantly high compared to those of BALB/c. C57BL/6 mice exhibited severe allergic vasculitis in the pulmonary arteries compared to BALB/c mice. The high concentrations of IL-4, IL-5, and IFN-γ in the lung may play a critical role in the pathogenesis of allergic vasculitis in C57BL/6 mice.

Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis

ObjectiveTo contrast the effect of the burden of vasculitis activity with the burden of adverse events on 1-year mortality of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).MethodsThis study assessed the...

Identification of Bartonella henselae in an Aborted Equine Fetus

This report describes the characterization of a Bartonella henselae abortion in an equine fetus by gross, histologic, immunohistochemical, ultrastructural, and molecular methods. Bartonella henselae can cause cat scratch disease, bacillary angiomatosis, bacillary peliosis, and endocarditis in humans and other animals. The bacterium has been isolated from several mammalian species but only recently from equids; however, it has not been linked to abortion in equids. An aborted equine fetus exhibited necrosis and vasculitis in multiple tissues, with intralesional Gram-negative short-to-spirillar bacteria. Nucleotide sequence analysis of the bacterial 16S rRNA gene amplified from the DNA extracted from fetal tissues revealed 99.9% homology to that of B. henselae. The presence of B. henselae in the fetal tissues was further confirmed by polymerase chain reaction amplification and nucleotide sequence analysis of other Bartonella species-specific genes. Microorganisms were immunohistochemically labeled with a monoclonal antibody to B. henselae and were ultrastructurally characterized. Attempts to detect known causative agents of equine abortion were unsuccessful. Given the severity of vasculitis and the presence of intralesional bacteria, we concluded that B. henselae infection caused the abortion of this foal.

Acute management of Kawasaki disease

Since its first English language description by Dr. Tomisaku Kawasaki in 1974, Kawasaki disease (KD) has become the leading cause of acquired heart disease among children in the United States [1]. The pathogenesis of KD involves a marked immune response to an unknown stimulus, resulting in high levels of cytokines, endothelial cell activation, and arteritis of the coronary arteries and occasionally other medium-sized muscular arteries. Patients in whom coronary ectasia, dilation, or aneurysm occur are at risk for coronary artery thrombosis, angina, myocardial infarction, and sudden death. Early in the illness, therapy is designed to reduce immune perturbations and severity of vasculitis. Ultimately, the aim of therapy is reducing the incidence of coronary sequelae. Aspirin therapy is initiated in the acute phase of KD at a dose of 80–100 mg/kg/day, divided into four daily doses. Many centers use high-dose aspirin only until the patient has been afebrile for 48 h, after which the dose is decreased to 3–5 mg/kg daily. Intravenous immune globulin (IVIG) has been shown to decrease the incidence of coronary artery aneurysms (CAA). A single high-dose (2 g/kg) is given at time of diagnosis and repeated if the patient is still febrile 36 h after initial infusion. There is a suggestion that pulsed-dose methylprednisolone, in addition to aspirin and IVIG as primary therapy results in faster resolution of fever, more rapid improvement in inflammatory markers, and shorter length of hospitalization. The effect, if any, on coronary artery abnormalities is not well established. A number of other therapies are also discussed in this review including plasma exchange, serine protease inhibitors, pentoxifylline, cytotoxic agents, tumor necrosis factor, and platelet glycoprotein IIb/IIIa.

Apoptosis and nitrative stress associated with phosphodiesterase inhibitor-induced mesenteric vasculitis in rats.

Nitric oxide may play a role in phosphodiesterase (PDE) inhibitor-induced rat mesenteric vasculitis. The present study was conducted to identify cellular sources of iNOS, determine the distribution of nitrotyrosine (NT) residues as a footprint of peroxynitrite (ONOO-) production, and evaluate their association with vascular apoptosis. To dissociate primary events from secondary changes associated with the inflammatory response, rats were given the PDE IV inhibitor CI-1018 orally at 750 mg/kg alone or concurrently with dexamethasone (DEX) intraperitoneally at 1 mg/kg for 4-5 days. Neutrophil (PMN) involvement in apoptosis was investigated in CI-1018 treated rats dosed with rabbit anti-rat PMN serum (APS). iNOS expression, NT residues, and caspase-3 were detected by immuno-histochemistry. Apoptosis was evaluated by TUNEL assay. CI-1018 induced vascular lesions were associated with iNOS expression in endothelial cells and inflammatory infiltrates; NT was evident only in the latter. Caspase-3 and TUNEL-positive staining were prominent only in medial smooth muscle cells (SMC) from CI-1018-treated rats and only when associated with active inflammation. iNOS- and NT-positive inflammatory cells were present in close proximity to SMC with caspase-3 staining. Inflammatory infiltrates were absent in rats given DEX with minimal SMC necrosis and hemorrhage remained. DEX eliminated apoptosis and immunoreactivity associated with caspase-3, iNOS, and NT. APS depletion of PMNs decreased the incidence and severity of vasculitis but failed to abolish completely caspase-3 immunoreactivity. Expression patterns for caspase-3, iNOS, and NT demonstrated that nitrative stress is a prominent feature of PDE inhibitor-induced vasculitis, with a possible role in medial SMC apoptosis. Further, medial SMC apoptosis may not be a primary event, but instead may be secondary to the inflammatory response.

Stem cell transplantation in primary systemic vasculitis

Many patients with various autoimmune diseases fail to respond to conventional immunosuppressive therapy and develop irreversible organ damage. In some cases the complications might be fatal. Furthermore, prolonged immunosuppression with cyclophosphamide or corticosteroids often leads to long-term side effects, cumulative organ damage, and development of secondary malignancies. Thus, short-term, high-dose immunosuppressive therapy with autologous stem cell transplantation might be an alternative for otherwise refractory patients. This concept has been used mainly in patients with scleroderma, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. Patients with primary systemic vasculitis (PSV) seem to be suitable candidates for high-dose chemotherapy (HDCT). Although complete, long-term remissions are possible with standard immunosuppressive therapy, there is a subgroup of patients who cannot be cured by standard therapy. They need long-term immunosuppression and eventually die due to progression of the disease or cumulative therapy-related toxicity. In large series, the 5-year mortality rate was > 20%. The severity of vasculitis rather than the distinction between subgroups should determine whether HDCT might be a life-saving treatment. Careful patient selection with the help of scoring systems and determination of the optimal time in the course of disease are now the major goals in the approach to HDCT. First reports as well as our own single-center experience in HDCT with a limited number of patients with severe PSV have shown that long-term remissions are possible even in patients refractory to conventional immunosuppression.

The role of endogenous steroid hormones in the generation of T helper 2-mediated autoimmunity in mercuric chloride-treated Brown-Norway rats.

Injection of Brown-Norway rats with mercuric chloride (HgCl2) activates a T helper type 2 (Th2) autoimmune response, with production of a number of autoantibodies and vasculitis primarily affecting the gut. Glucocorticoids have been shown to suppress Th1 and to promote the development of Th2-type responses. Conversely dehydroepiandrosterone (DHEA) promotes Th1 responses with suppression of Th2 responses. This study set out to define the role of these hormones in this animal model. Rats were adrenalectomized (Adx) with no steroid replacement (n = 11), Adx with basal steroid replacement given by a 25 mg corticosterone pellet inserted subcutaneously (n = 13), or sham-Adx (n = 14) prior to administration of HgCl2. In both groups of Adx animals there was a delay in the production of immunoglobulin E (IgE) and serum concentrations on day 9 were marginally lower (P = 0.035, repeated measures ANOVA). All of the animals Adx with no steroid replacement and two Adx animals with steroid replacement died between 10 and 14 days after HgCl2 challenge. There was no difference in the severity of caecal vasculitis between the groups. A significant increase in adrenal size was noted following administration of HgCl2. Administration of subcutaneous DHEA implants (100 mg and 200 mg) had no significant effect on IgE concentrations or severity of vasculitis. These observations do not support the hypothesis that corticosterone and DHEA play a central role in setting the Th1/Th2 balance in this experimental Th2-mediated autoimmune disease; in contrast with the Th1-mediated autoimmune disease experimental allergic encephalomyelitis where corticosterone plays a key role in immunoregulation.