Successful rituximab treatment of granulomatous/lymphocytic interstitial lung disease in common variable immunodeficiency.

Successful rituximab treatment of granulomatous/lymphocytic interstitial lung disease in common variable immunodeficiency Common variable immunodeficiency, a heterogeneous group of diseases, represents a clinically relevant form of antibody immunodeficiency. Granulomatous/lymphocytic interstitial lung disease is among the most serious complications. A case report is presented of a young women with granulomatous/lymphocytic interstitial lung disease and splenomegaly accompanied by pancytopenia. Intravenous rituximab treatment in monotherapy (at a weekly dose of 375 mg/m2 for four consecutive weeks, repeated six months later) not only led to a significant improvement in clinical symptoms but also to positive morphological and functional lung changes, mitigation of pancytopenia, considerable reduction of alkaline phosphatase level, and disappearance of splenic granulomas. The treatment was well tolerated without any side effects. The case report presented suggests possible efficacy and safety of rituximab monotherapy in patients with a complicated form of common variable immunodeficiency. KEYWORDS Rituximab - antibody immunodeficiency - lung disease - treatment Epidemiol. Mikrobiol. Imunol., 67, 2018, c. 3, s. 142-148.

Antibodies against Pneumococcal Capsular Polysaccharides and Natural Anti-Galactosyl (Alpha-Gal) in Patients with Humoral Immunodeficiencies.

Humoral deficiencies represent a broad group of disorders. The aim of the study was to compare the levels of antibodies against pneumococcal capsular polysaccharides (anti-PCP) and natural anti-galactosyl (anti-Gal) antibodies in (1) patients with chronic lymphocytic leukaemia (CLL), (2) patients with common variable immunodeficiency (CVID), and (3) a healthy population and to explore their diagnostic and prognostic potential. Serum immunoglobulin levels and levels of anti-Gal IgG, IgA, and IgM and anti-PCP IgG and IgG2 were determined in 59 CLL patients, 30 CVID patients, and 67 healthy controls. Levels of IgG, IgA, IgM, anti-Gal IgA, anti-Gal IgM, and anti-PCP IgA were lower in CLL and CVID patients than in healthy controls (p value for all parameters < 0.0001). Decrease in the levels of IgA, IgM, anti-Gal IgA, and anti-PCP IgA was less pronounced in the CLL group than in the CVID group. IgA decline, anti-Gal IgA, anti-PCP IgA, and anti-PCP IgG2 were negatively correlated with CLL stage. We devise the evaluation of anti-Gal antibodies to be a routine test in humoral immunodeficiency diagnostics, even in cases of immunoglobulin substitution therapy. Significant reductions, mainly in anti-Gal IgA, IgM, and anti-PCP IgA levels, may have prognostic importance in CLL patients.

[Recurrent meningitis and inherited complement deficiency]. / Recidivující meningitidy a vrozený deficit komplementového systému.

Complement deficiency represents 5% of primary immunodeficiencies worldwide. A total of seven patients with deficiencies of the classical complement pathway were reported in the Czech Republic by the end of 2015. Typical manifestations of complement deficiency are recurrent meningitis, other bacterial infections, autoimmunity and kidney disease.Two case reports are presented of patients with molecularly confirmed C7 (compound heterozygote, c.663_644del in exon 6 and c.2350+2T:>C in intron 16) and C8 (homozygous c.1282C>T in exon 9) deficiency. The first patient had four attacks of meningococcal meningitis and an episode of pneumonia of unknown aetiology in childhood. The second had six attacks of meningitis. He also suffered from recurrent infections (otitis media, tonsillitis, chronic mucopurulent rhinitis and subsequent pansinusitis complicated by nasal polyposis) since childhood. No autoimmune disease was documented in either patient. They both received meningococcal and pneumococcal vaccines. Antibiotic prophylaxis was used only in the second patient, leading to a decline in the number of ENT infections.Complement deficiency should be suspected in patients with recurrent meningococcal infections, especially if combined with other infections caused by encapsulated bacteria or autoimmunity diseases. Prophylaxis with conjugate polysaccharide vaccines is recommended and antibiotic prophylaxis should be considered in individual cases.

Spectrum and management of complement immunodeficiencies (excluding hereditary angioedema) across Europe.

INTRODUCTION: Complement immunodeficiencies (excluding hereditary angioedema and mannose binding lectin deficiency) are rare. Published literature consists largely of case reports and small series. We collated data from 18 cities across Europe to provide an overview of primarily homozygous, rather than partial genotypes and their impact and management. METHODS: Patients were recruited through the ESID registry. Clinical and laboratory information was collected onto standardized forms and analyzed using SPSS software. RESULTS: Seventy-seven patients aged 1 to 68 years were identified. 44 % presented in their first decade of life. 29 % had C2 deficiency, defects in 11 other complement factors were found. 50 (65 %) had serious invasive infections. 61 % of Neisseria meningitidis infections occurred in patients with terminal pathway defects, while 74 % of Streptococcus pneumoniae infections occurred in patients with classical pathway defects (p < 0.001). Physicians in the UK were more likely to prescribe antibiotic prophylaxis than colleagues on the Continent for patients with classical pathway defects. After diagnosis, 16 % of patients suffered serious bacterial infections. Age of the patient and use of prophylactic antibiotics were not associated with subsequent infection risk. Inflammatory/autoimmune diseases were not seen in patients with terminal pathway, but in one third of patients classical and alternative pathway defects. CONCLUSION: The clinical phenotypes of specific complement immunodeficiencies vary considerably both in terms of the predominant bacterial pathogen, and the risk and type of auto-inflammatory disease. Appreciation of these phenotypic differences should help both immunologists and other specialists in their diagnosis and management of these rare and complex patients.

[Good's syndrome (thymoma associated hypogammalobulinaemia) - 2 case reports]. / Gooduv syndrom (s thymomem spojená hypogamaglobulinemie) - 2 kazuistiky.

Although tumours of the thymus are rare, they are common among neoplasms of the anterior superior mediastinum. They usually exhibit indolent behavior, but do have the capacity to invade surrouding structures. Their metastatic potential is low. Paraneoplastic complications including autoimmune disorders (frequently myastenia, cytopenia) or combined immunodeficiency are of clinical significance. Here we report two case reports of thymoma patients associated with secondary immunodeficiency known as Goods syndrom. The first case exhibited as symptomatic combinated immunodeficiency with oral lichen planus. Thymoma findings was accidental. Severity of immunodeficiency required long-term intravenous immunoglobulins supplementations, even after complete surgical resection. On the other hand, the second case manifested by signs of advanced local tumour growth. Antibiotic prophylaxis was selected as immunodeficiency treatment.

[Hereditary angioedema--neglected diagnosis]. / Hereditární angioedem--opomíjená diagnóza.

Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare autosomal dominant inherited disorder. It is characterized by recurrent episodes of potentially life-threatening swellings without itching localized in the dermis and submucosa. We report a case of 41 years old woman with hereditary angioedema manifested as episodes of localized skin swellings and painful gastrointestinal colics. This report underlines the fact that hereditary angioedema is underdiagnosed in differential diagnoses. If hereditary angioedema is correctly diagnosed, effective treatment highly improving patients' quality of life is available.

Renal tubular dysfunction and urinary zinc excretion in breast cancer patients treated with anthracycline-based combination chemotherapy.

The survival of breast cancer patients has significantly improved through the treatment with anthracyclines. Although anthracyclines are known to produce renal disease in experimental animals, little is known about the toxicity of anthracyclines at clinically relevant doses in humans. In a previous study on cancer patients we have observed an increase in the urinary activity of N-acetyl-beta-D-glucosaminidase (NAG), an indicator of renal tubular cell dysfunction that was accompanied by increased urinary zinc loss. Because an increase in NAG activity was reported after the treatment with anthracyclines, we hypothesized that an increase in urinary NAG activity in breast cancer patients treated with anthracycline-based regimens will be accompanied by hyperzincuria and hypozincemia. Urinary and serum zinc, urinary NAG and serum creatinine were examined during chemotherapy in 26 breast cancer patients treated with anthracycline-based chemotherapy. A trend for increased NAG activity, as compared to baseline, was observed throughout the first 4 cycles of treatment. NAG activity was significantly elevated compared to pretreatment levels one week after the first, third and fourth dose of chemotherapy. Serum creatinine concentrations decreased significantly after the second cycle of therapy. On the other hand, urinary and serum zinc levels did not change significantly during the treatment. In conclusion, our data confirm the presence of mild renal tubular cell dysfunction in breast cancer patients treated with doxorubicin-based chemotherapy. Increased urinary NAG is accompanied by a decrease in serum creatinine which is consistent with hyperfiltration. These changes are not associated with abnormalities of renal zinc handling or a decrease in serum zinc concentrations.

CD4+ T-lymphocytopenia and systemic immune activation in patients with primary and secondary liver tumours.

Using flow cytometry, we evaluated peripheral blood leucocyte subsets in 84 patients with primary and secondary liver cancer. The patients had significantly lower absolute (659+/-386 vs. 906+/-360 cells per microl, p=0.004) numbers of CD3+ CD4+, relative (9+/-5 vs. 12+/-4%, p=0.02) and absolute (154+/-115 vs. 221+/-83 cells per microl, p=0.02) numbers of CD8+ CD28+, absolute numbers of CD3+ and relative and absolute numbers of CD19+. Relative and absolute numbers of CD3+ DR+, CD3+ CD69+ and CD14+ CD16+ cells were significantly elevated in patients compared to controls. The phenotype was similar in 54 patients exposed to chemotherapy compared to 30 untreated patients. Urinary neopterin, a marker of systemic immune activation, was significantly higher in patients with liver tumours compared to controls. A negative correlation was observed between urinary neopterin and the absolute numbers of CD3+ CD4+ (Spearman rank correlation coefficient, rs = -0.54, p<0.0025) and CD19+ (rs = -0.49, p<0.01) in untreated patients. We conclude that, independently of prior chemotherapy, patients with liver present with markedly decreased numbers of CD3+ CD4+ lymphocytes as well as with other abnormalities of peripheral blood leukocyte phenotype. Similar to patients with human immunodeficiency virus infection, the decrease in CD3+ CD4+ lymphocytes is associated with systemic immune activation.

Intestinal permeability in patients with chemotherapy-induced stomatitis.

PURPOSE: Mucositis represents one of the most common side effects of chemotherapy, and may affect any part of the gastrointestinal tract, resulting in stomatitis, dysphagia, dyspepsia, or diarrhea. The aim of the present study was to evaluate intestinal permeability in patients with stomatitis during treatment with oral granulocyte-monocyte colony-stimulating factor (GM-CSF, Leucomax). METHODS: Ten patients with chemotherapy-induced stomatitis and 21 control cancer patients were included in the study. Intestinal permeability in patients with stomatitis was evaluated before and after the treatment with oral GM-CSF (200 micrograms for 4 consecutive days) by measuring urinary lactulose, D-xylose, and mannitol after oral challenge in collected urine using capillary gas chromatography. RESULTS: Mean grade of stomatitis (3, range 2-3) improved during treatment by a mean of 1 grade (range 0-2, sign test P < 0.05) with an improvement observed in eight of ten patients. Lactulose excretion, lactulose/mannitol, and lactulose/xylose ratios were markedly elevated in the patients with mucositis compared with 21 control cancer patients (1.60 +/- 1.04%, 0.2446 +/- 0.2937, and 0.3877 +/- 0.6808 vs 0.35 +/- 0.20%, 0.0332 +/- 0.0148, and 0.0255 +/- 0.0086, respectively, Mann Whitney U-test, P < 0.001). After treatment, lactulose excretion, lactulose/mannitol, and lactulose/xylose ratio decreased significantly (1.60 +/- 1.04 vs 0.63 +/- 0.42%; 0.2446 +/- 0.2937 vs 0.1303 +/- 0.1149; and 0.3877 +/- 0.6808 vs 0.1126 +/- 0.1146, respectively, P < 0.05). CONCLUSIONS: Lactulose excretion after oral challenge, lactulose/mannitol, or lactulose/xylose ratio may be useful markers for intestinal involvement in chemotherapy-induced mucositis. Improvement of oral mucositis was associated with a significant decrease of intestinal permeability to lactulose. Testing of intestinal permeability by the present method may be useful to evaluate the effect of therapeutic interventions in patients with chemotherapy-induced mucositis.