A Fatal Case of Atypical Disseminated Herpes Zoster in a Patient with Meningoencephalitis and Seizures Associated with Steroid Immunosuppression.

BACKGROUND Herpes zoster is caused by the reactivation of the varicella zoster virus (VZV) and usually presents with vesicular skin lesions with a dermatomal distribution. Disseminated herpes zoster (DHZ) infection is characterized by non-dermatomal skin eruptions, often with involvement of other organs, and occurs in immunocompromised patients. CASE REPORT A 69-year-old man who was treated with prednisolone for amiodarone-associated interstitial lung disease, presented with seizures and altered consciousness. He had an erythematous rash with raised vesicles involving the skin of the genital region, left thigh, and abdomen. Following a diagnosis of DHZ with herpes zoster meningoencephalitis, he was treated with intravenous acyclovir. However, his level of consciousness did not improve, and he died of respiratory failure due to aspiration pneumonia. CONCLUSIONS A diagnosis of DHZ should be considered in immunosuppressed patients treated with steroids who present with seizures. A detailed search for skin eruptions should be conducted to enable early diagnosis and treatment.

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis: potential implications for macrophages and follicle maturation.

Endometriosis is an estrogen dependent chronic inflammation and thus a condition of stress. Though the G-protein coupled estrogen receptor (GPER) has been shown to be up-regulated in ovarian endometriosis, insights involved in inducing this receptor expression are largely elusive. Therefore, this study investigated whether stress-related factors (ACTH, prednisolone) or inflammatory factors (IL-1ß, TNFα, and PGE(2)) factors may affect GPER. To further link GPER to endometriosis pathophysiology it was tracked in macrophages and follicles of endometriotic ovaries. This study found GPER expression to be modulated by stress-related hormones as well as inflammation and to be up-regulated in endometriosis-associated macrophages. At the same time, follicles of ovaries affected by endometriosis presented significantly reduced GPER positivity when compared to controls, suggesting a possible way by which endometriosis may affect folliculogenesis. The multiple roles of GPER as presented herein make it a promising future candidate for targeted molecular endometriosis treatment.

Long-term immunosuppressive therapy with cyclosporine plus prednisolone for necrotizing meningoencephalitis in a Pekingese dog.

A 4-year-old intact female Pekingese dog was presented with ataxia and seizure episodes. Based on magnetic resonance imaging and cerebrospinal fluid analysis results, meningoencephalitis of unknown etiology was suspected. The present case survived for 1,096 days under cyclosporine plus prednisolone therapy and was definitively diagnosed with necrotizing meningoencephalitis. This report describes the clinical findings, serial magnetic resonance imaging characteristics and pathologic features of a necrotizing meningoencephalitis and long-term survival after cyclosporine with prednisolone therapy.

Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study.

OBJECTIVE: To clarify the association of clinical and prognostic features with dermatomyositis (DM)-specific autoantibodies (Abs) in adult Japanese patients with DM. DESIGN: Retrospective study. SETTING: Kanazawa University Graduate School of Medical Science Department of Dermatology and collaborating medical centers. Patients A total of 376 consecutive adult Japanese patients with DM who visited our hospital or collaborating medical centers between 2003 and 2008. MAIN OUTCOME MEASURES: Clinical and laboratory characteristics of adult Japanese patients with DM and DM-specific Abs that include Abs against Mi-2, 155/140, and CADM-140. RESULTS: In patients with DM, anti-Mi-2, anti-155/140, and anti-CADM-140 were detected in 9 (2%), 25 (7%), and 43 (11%), respectively. These DM-specific Abs were mutually exclusive and were detected in none of 34 patients with polymyositis, 326 with systemic sclerosis, and 97 with systemic lupus erythematosus. Anti-Mi-2 was associated with classical DM without interstitial lung disease or malignancy, whereas anti-155/140 was associated with malignancy. Patients with anti-CADM-140 frequently had clinically amyopathic DM and rapidly progressive interstitial lung disease. Cumulative survival rates were more favorable in patients with anti-Mi-2 compared with those with anti-155/140 or anti-CADM-140 (P < .01 for both comparisons). Nearly all deaths occurred within 1 year after diagnosis in patients with anti-CADM-140. Conclusion Dermatomyositis-specific Abs define clinically distinct subsets and are useful for predicting clinical outcomes in patients with DM.

Immediate-type hypersensitivity to succinylated corticosteroids.

BACKGROUND: Despite their frequent use, systemic corticosteroids have rarely elicited immediate-type reactions. OBJECTIVE: We report two male patients, aged 26 and 70 years, respectively, with severe immediate-type hypersensitivity secondary to the administration of corticosteroids esterified with succinate. METHODS: Skin tests, basophil activation tests and challenge tests were performed for diagnostic evaluation. RESULTS: In both patients, immediate-type skin test reactions were found to methylprednisolone sodium hemisuccinate (MSH) and prednisolone sodium hemisuccinate (PSH). In contrast, nonsuccinylated corticosteroids (including methylprednisolone and prednisolone in one patient) yielded no test reactions. Basophils from one patient exhibited a stimulated expression of the activation marker CD63 upon in vitro incubation with PSH or hydrocortisone sodium succinate, but not with hydrocortisone. Skin tests and basophil activation tests were negative in controls. One patient was challenged with the incriminated drugs. He developed flush, conjunctivitis, tachycardia and dyspnea 2 min after injection of MSH, and dyspnea shortly after intravenous administration of PSH. Oral and intravenous challenge tests with nonsuccinylated corticosteroids were tolerated well by both patients. CONCLUSIONS: These case reports should alert clinicians to rare, but severe immediate-type reactions to corticosteroids, related to the succinate moiety in our patients. In case of allergic reactions to corticosteroids, it is mandatory to identify the causative agent and find safe alternatives.

Case of herpes zoster duplex bilateralis.

Non-contiguously simultaneous development of herpes zoster is very rare. It is named either herpes zoster duplex unilateralis or bilaterarlis, depending on whether one or both sides of the body are involved. Herein, we report a 21-year-old man, who had been treated for ulcerative colitis with prednisolone, and presented with painful grouped vesicles of the lower abdomen and back in a relatively symmetrical distribution. A Tzanck smear and punch biopsy were performed on the vesicles of the back. We report a rare case of symmetrical herpes zoster duplex bilateralis.

Risk factors of Pneumocystis jeroveci pneumonia in patients with systemic lupus erythematosus.

Pneumocystis jeroveci pneumonia (PCP) is an opportunistic infection which occurs mostly in the immune-deficiency host. Although PCP infected systemic lupus erythematosus (SLE) patient carries poor outcome, no standard guideline for prevention has been established. The aim of our study is to identify the risk factors which will indicate the PCP prophylaxis in SLE. This is a case control study. A search of Ramathibodi hospital's medical records between January 1994 and March 2004, demonstrates 15 cases of SLE with PCP infection. Clinical and laboratory data of these patients were compared to those of 60 matched patients suffering from SLE but no PCP infection. Compared to SLE without PCP, those with PCP infection have significantly higher activity index by MEX-SLEDAI (13.6 +/- 5.83 vs. 6.73 +/- 3.22) or more renal involvement (86 vs. 11.6%, P < 0.01), higher mean cumulative dose of steroid (49 +/- 29 vs. 20 +/- 8 mg/d, P < 0.01), but lower lymphocyte count (520 +/- 226 vs. 1420 +/- 382 cells/mm(3), P < 0.01). Interestingly, in all cases, a marked reduction in lymphocyte count (710 +/- 377 cells/mm(3)) is observed before the onset of PCP infection. The estimated CD4+ count is also found to be lower in the PCP group (156 +/- 5 vs. 276 +/- 8 cells/mm(3)). Our study revealed that PCP infected SLE patients had higher disease activity, higher dose of prednisolone treatment, more likelihood of renal involvement, and lower lymphocyte count as well as lower CD4+ count than those with no PCP infection. These data should be helpful in selecting SLE patients who need PCP prophylaxis.

Prednisolone suppresses NK cell cytotoxicity in vitro in women with a history of infertility and elevated NK cell cytotoxicity.

PROBLEM: To evaluate the effect of prednisolone on NK cell cytotoxicity in vitro environment and also to compare the effect of prednisolone versus immunoglobulin-G (IVIG) on NK cell cytotoxicity using in vitro co-culture with K562 cells. METHOD OF STUDY: The following is a prospective observational study, between August 2006 and February 2007, was carried out on blood samples from 110 patients with a history of recurrent miscarriage or recurrent failed implantation. Peripheral blood mononuclear cells containing NK cells were isolated and co-cultured with target cell K562 in three different effector-to-target (E:T) ratios of 50:1, 25:1 and 12.5:1. Prednisolone or IVIG was then added to the tube with E:T ratio of 50:1 to assess suppressive effect. The percentage killing was recorded and statistical analysis performed using Student's t-test. RESULTS: In the experiments with an E:T ratio of 50:1 without prednisolone or IVIG in the co-culture, the mean target cell killing percentage was 26.4%. In cultures using the same E:T ratio, this killing percentage was significantly reduced in the presence of IVIG (9.9%) or prednisolone (13.6%), (P<0.001 in both analyses). On comparing the reduction in killing percentage of target cells by prednisolone versus IVIG, a slightly lower reduction in the prednisolone co-culture was noted but this was not statistically significant (P>0.05). CONCLUSION: The results of this study show that prednisolone is able to suppress the cytolytic activity of the NK cell. Prednisolone and IVIG are almost equally effective in suppressing in vitro NK cell cytolytic activity.

Comparison of megadose methylprednisolone versus conventional dose prednisolone in hematologic disorders.

Glucocorticoids (GCs) are known for their clinically useful effects in immunologic and inflammatory disorders. Although there is a huge volume of knowledge concerning the cellular and molecular effects of GCs, statements regarding their effects in multiple diseases at variable doses are not clear-cut owing to pharmacogenetic differences. The main actions of GCs in hematologic disorders have been related to their differentiation-inducing and apoptosis-inducing effects, but modification of several steps of the hematopoietic and/or immune pathway has also been reported. In our clinic, mega-dose methylprednisolone (MDMP) has been successfully used for treatment of different hematologic diseases, such as leukemias, bone marrow failure in aplastic anemia, hypoplastic anemia, myelodysplastic syndrome, neutropenia, autoimmune diseases, and in some congenital hereditary diseases. Both clinical and experimental studies in our department revealed that MDMP was more effective than conventional dose steroids. It is interesting that MDMP can be curative in some congenital hereditary diseases such as Diamond-Blackfan syndrome. However, more research is required to clarify their roles in biology, physiology, and molecular genetics.

Alteration of the cortisol-cortisone shuttle in leprosy type 1 reactions in leprosy patients in Hyderabad, India.

Regulation of inflammation in leprosy may be influenced by local concentrations of active cortisol and inactive cortisone, whose concentrations are regulated by enzymes in the cortisol-cortisone shuttle. We investigated the cortisol-cortisone shuttle enzymes in the skin of leprosy patients with type 1 reactions (T1R), which are characterised by skin and nerve inflammation. Gene expression of the shuttle enzymes were quantified in skin biopsies from 15 leprosy patients with new T1R before and during prednisolone treatment and compared with levels in skin biopsies from 10 borderline leprosy patients without reactions. Gene expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2, which converts cortisol to cortisone, is down-regulated in skin from T1R lesions. However expression levels of 11beta-HSD type 1, which converts cortisone to cortisol, were similar in skin with and without reactions and did not change during anti-leprosy drug treatment. Prednisolone treatment of patients with reactions is associated with an upregulation of 11beta-HSD2 expression in skin. The down regulation of 11beta-HSD2 at the beginning of a reaction may be caused by pro-inflammatory cytokines in the leprosy reactional lesion and may be a local attempt to down-regulate inflammation. However in leprosy reactions this local response is insufficient and exogenous steroids are required to control inflammation.

Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis.

OBJECTIVE: To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax) in controls and patients with established rheumatoid arthritis (RA) treated with TNF blockers, methotrexate (MTX) or a combination of both. METHODS: Patients with RA (n = 149) and healthy controls (n = 47) were vaccinated. Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50 patients, and 62 patients were treated with TNF blockers alone or with other DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An immune response was defined as a twofold or higher increase in antibody concentration following vaccination. RESULTS: Prevaccination antibody levels for both 23F and 6B were similar in the patient groups. Antibody concentrations after vaccination increased significantly in all groups. Patients treated with TNF blockers without MTX showed better immune responses than those treated with TNF blockers in combination with MTX (P = 0.037 for 23F and P = 0.004 for 6B) or MTX alone (P<0.001 for both 23F and 6B). RA patients given MTX alone had the lowest immune responses. Prednisolone treatment did not influence the responses. CONCLUSIONS: Patients treated with TNF blockers and controls showed similar responses to vaccination. In contrast, patients treated with MTX had reduced responses regardless of anti-TNF treatment. The findings do not argue against the use of pneumococcal vaccination in RA patients undergoing treatment with TNF blockers.

Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: a phase 2 clinical trial in Uganda.

Background. Human immunodeficiency virus (HIV)-infected patients with tuberculosis (TB) respond to effective antituberculous therapy, but their prognosis remains poor. Mounting evidence from clinical studies supports the concept of copathogenesis in which immune activation that is triggered by TB and mediated by cytokines stimulates viral replication and worsens HIV infection, especially when immune function is preserved.Methods. We performed a phase 2, randomized, double-blind, placebo-controlled clinical trial in Kampala, Uganda, to determine whether immunoadjuvant prednisolone therapy in HIV-infected patients with TB who have CD4(+) T cell counts >/=200 cells/ mu L is safe and effective at increasing CD4(+) T cell counts.Results. Short-term prednisolone therapy reduced levels of immune activation and tended to produce higher CD4(+) T cell counts. Although prednisolone therapy was associated with a more rapid clearance of Mycobacterium tuberculosis from the sputum, it was also associated with a transient increase in HIV RNA levels, which receded when prednisolone therapy was discontinued. The intervention worsened underlying hypertension and caused fluid retention and hyperglycemia.Conclusion. The benefits of prednisolone therapy on immune activation and CD4(+) T cell counts do not outweigh the risks of adverse events in HIV-infected patients with TB and preserved immune function.

Pulmonary strongyloidiasis in a patient receiving prednisolone therapy.

Strongyloidiasis is widely distributed in tropical and subtropical areas. Disseminated strongyloidiasis may develop in patients with immunodeficiencies. In the absence of early diagnosis and treatment, the prognosis of disseminated strongyloidiasis is extremely poor. We report a case of pulmonary strongyloidiasis that was successfully treated. The patient was an 83-year-old woman who had been receiving long-term oral prednisolone therapy for uveitis. The patient visited our emergency department complaining of breathing difficulties and diarrhea. A chest X-ray revealed a diffuse enhancement of interstitial shadows. A bronchoalveolar lavage (BAL) was performed, and both Gram staining and Grocott's staining revealed the presence of multiple filariform larvae of Strongyloides stercoralis in the bronchoalveolar lavage fluid (BALF). A stool examination performed at the same time also yielded S. stercoralis. The patient was diagnosed as having pulmonary strongyloidiasis and was treated with thiabendazole and ivermectin, in addition to antimicrobial agents; her respiratory symptoms and diarrhea improved, and S. stercoralis was not detected in subsequent follow-up examinations thereafter. In endemic areas of S. stercoralis, pulmonary strongyloidiasis should be considered as part of a differential diagnosis if chest imaging findings like alveolar and interstitial shadow patterns or lobar pneumonia are seen in patients with immunodeficiencies.

Th1 cytokine pattern (IL-12 and IL-18) in bronchoalveolar lavage fluid (BALF) before and after treatment with interferon gamma-1b (IFN-gamma-1b) or colchicine in patients with idiopathic pulmonary fibrosis (IPF/UIP).

BACKGROUND AND AIM: Characterization of the biologic effects of Th1 cytokines will enhance the understanding of idiopathic pulmonary fibrosis (IPF) pathogenesis and treatment selection. Th1 response is characterized by increased expression of IFN-gamma, interleukin (IL)-12 and IL-18. The present study aims to evaluate the role of Th1 cytokines and their possible changes in the bronchoalveolar lavage fluid (BALF), before and after treatment with IFN-gamma-1b or colchicine. PATIENTS AND METHODS: We studied prospectively 10 patients (8 male, 2 female) of median age 67 yr with histologically confirmed IPF/UIP. Patients were randomly assigned to receive either IFN-gamma-1b 200 microg sc (5 patients) or colchicine 1 mg qd (5 patients) plus prednisone 10 mg qd. BALF IL-12 and IL-18 levels were measured before and after treatment. RESULTS: BALF IL-12 levels before and after treatment did not differ significantly between the two treatment groups. However, BALF IL-18 levels were significantly decreased after treatment with IFN-gamma-1b (mean +/- SD, 58.4 +/- 15.6 pg/mL vs 42.8 +/- 4.90 pg/mL, p < 0.05). A significant difference was also found after treatment with colchicine (mean +/- SD, 66.8 +/- 36.9 pg/mL vs 42.6 +/- 1.08 pg/mL, p < 0.01). A significant correlation was found between IL-18 BALF levels and the BALF neutrophils (r = 0.75, p = 0.024). CONCLUSION: Our data suggest the potential role of IL-18 as an inflammatory marker in the pathogenetic pathway of IPF such as its possible downregulation by IFN-gamma-1b treatment. Further studies are needed in a higher number of patients in order to define the precise role of both cytokines during the immunoregulatory response with IFN-gamma-1b.

Persistent infection of Mongolian jirds with a non-pathogenic trypanosome, Trypanosoma (Herpetosoma) grosi.

Non-pathogenic trypanosomes of the subgenus Herpetosoma are normally host specific, and laboratory models include Trypanosoma lewisi in rats and Trypanosoma musculi in mice. Two isolates of Trypanosoma grosi, originating from Apodemus agrarius and Apodemus peninsulae, grew well in Mongolian jirds, Meriones unguiculatus, after intraperitoneal inoculation of 2 x 10(5) or a minimum 500 bloodstream forms. The course of T. grosi infection in jirds resembled T. musculi infection in mice, rather than T. lewisi infection in rats. At week 2 to 3 p.i. trypanosomes disappeared from the bloodstream, and neither prednisolone treatment nor splenectomy prevented parasite elimination from the bloodstream. However, these treatments induced a marked increase in peak parasite counts. Regardless of prednisolone treatment or splenectomy, all jirds after day 21 p.i. became resistant to the reinfection. Although no trypanosomes were detected in the bloodstream of recovered jirds, dividing parasites persisted in the medullary capillaries of the kidney, like T. musculi infection in mice. We propose the T. grosi infection in jirds as an additional laboratory model for the study of non-pathogenic trypanosomes.

Treatment of autoimmune hepatitis.

Corticosteroid therapy is effective in all forms of autoimmune hepatitis, and the combination of prednisone and azathioprine is preferred. Remission can be achieved in 80% of patients within 3 years, and the 10- and 20-year survival rates exceed 80%. Histological cirrhosis does not affect response or longevity, and all patients with severe disease should be treated, including children, elderly adults, postmenopausal women, individuals with acute or fulminant presentations, and those without conventional autoantibodies. Relapse is common, and long-term low-dose prednisone or azathioprine therapy is preferred after multiple relapses. Sustained remission is achievable, even after relapse, in 47% within 10 years, and the long-term maintenance regimens need not be indefinite. Liver transplantation is effective, and its actuarial 10-year survival rate is 75%. Drugs such as cyclosporine, tacrolimus, and mycophenolate mofetil promise greater blanket immunosuppression, and site-specific interventions are feasible, including blocking peptides, soluble cytotoxic T lymphocyte antigen-4, cytokine manipulations, T cell vaccination, oral tolerance, and gene therapy.

Protection of mice from lethal endogenous Candida albicans infection by immunization with Candida membrane antigen.

The protective effects of immunization with Candida membrane antigen (CMA) on a systemic infection originating from intestinally colonized Candida albicans were examined. The colonization of orally inoculated C. albicans in the intestinal tract was established in BALB/c mice that had been concomitantly treated with oral doses of antibacterial drugs. In these animals, a systemic dissemination of C. albicans with fatal outcome was induced by a repeated dosing of prednisolone. In this endogenous infection model, the effects of immunization by CMA on the infection were examined. CMA-immunized mice showed a longer lifespan than unimmunized mice. The protective effect of CMA immunization in immunosuppressed mice was also measured by a decrease in body weight loss after treatment with prednisolone and in the number of viable Candida cells in the target organs, the kidneys and livers. However, the CFU of C. albicans in the intestinal tract was not significantly lowered. These results suggest that CMA immunization inhibited the dissemination of systemic Candida infection from the intestinal tract induced by treatment with prednisolone.