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Background Thymomas are known to be associated with myasthenia gravis and Good syndrome. Good syndrome is the association of thymoma with combined B cell and T cell immunodeficiency. The combination of all three diseases has not been reported. We discuss the therapeutic dilemma of immunosuppression in such a case. Case presentation A 27-year-old Sinhalese man was evaluated for persistent cough which was associated with pleuritic chest pain and was found to have pleural-based lesions in his left hemithorax. Further evaluation confirmed these lesions to be implants from a thymoma. He subsequently developed myasthenia gravis and impending myasthenic crisis precipitated by pneumonia. He was found to have hypogammaglobulinemia with low B cell counts, confirming a diagnosis of Good syndrome. Treatment with intravenously administered broad-spectrum antibiotics, acetylcholinesterase inhibitors, orally administered glucocorticoids, plasma exchange, and intravenous immunoglobulin led to clinical improvement. He subsequently underwent thymectomy and debulking of the tumor and was maintained on regular intravenous immunoglobulins combined with low-dose prednisolone. Conclusions Regular intravenous immunoglobulins combined with low-dose immunosuppression in addition to thymectomy appear to be safe when myasthenia gravis occurs in association with Good syndrome.

Background Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka. Methods Patients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone. Results One-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1–86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1–86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28–71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88–9.09) and deaths (OR = 2.38; 95% CI = 0.67–8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested. Conclusions NMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.

Background Hyper IgE recurrent infection syndrome (HIES) is a rare immune deficiency, characterized by recurrent staphylococcal skin and lung abscesses, pneumonia and increased IgE levels. The majority of autosomal dominant HIES (AD HIGE) is due to hypomorphic mutations in the signal transducer and the activator of transcription 3 (STAT3) gene. Case presentation Five patients were diagnosed with HIES, based on the clinical criteria and scoring system developed at the National Institutes of Health (NIH), USA. The STAT3 gene was sequenced and previously described mutations were identified in all five patients. We compare the clinical features of our patients with those from Asia, Europe and the US. Conclusion Even though the number of patients is limited, there are some clinical differences in patients from South Asia compared to European and even East Asian patients. However, the mutations detected are located at hot spots seen in western and Asian patients with AD HIGE.

Background Allergy to Vespa affinis venom is common in the Asia Pacific region. Venom preparations for diagnosis are not commercially available for this species. Methods The prominent allergens in V. affinis venom were identifiedusing immunochemical methods. Use of ImmunoCAP of Vespula vulgaris crude venom/its components and a passive basophil activation test (BAT) in the diagnosis of patients who had anaphylaxis to V. affinis venom (n = 30) were also accessed. The IgE double-positivity rates (positive to both hornet and honeybee) in ImmunoCAP and the passive BAT were determined. Results High IgE reactivity was seen with the five allergens in V. affinis venom; 96% (29/30) for 34 and 24 kDa, 93% (28/30) for 45 kDa and 90% (27/30) reactivity for the 100 and 80 kDa respectively. IgE cross-reactivity was low with ImmunoCAP using V. vulgaris venom (43%; 13/30) and Ves v1 (3%; 1/30), but relatively high with Ves v5 (73%; 22/30). All patients (100%) were positive to V. affinis venom in passive BAT. In ImmunoCAP, a high double-positivity rate (76%; 23/30) was detected while no double-positivity was detected in passive BAT. Conclusions High IgE reactivity for five allergens of V. affinis points to the potential of using these allergens in component resolved diagnosis (CRD). The passive BAT has shown its importance as a promising diagnostic tool with high accuracy. It would be particularly useful in cases with doubtful double-positive results of other diagnostic tests.

Diagnostic and therapeutic reagents are unavailable for anaphylaxis arising from stings by Apis dorsata. Venom profiles and cross-reactivity of A. dorsata and Apis mellifera were compared, to ascertain whether venom of A. mellifera can be used for diagnosis in A. dorsata allergy. Both venom profiles were similar by High Performance Liquid Chromatography and SDS-PAGE. Sera of 29 of 30 (96.7%) patients with anaphylaxis to A. dorsata stings had IgE to the phospholipase-2 (PLA2) doublet (15 and 16 kDa) of A. dorsata venom by immunoblot, compared to 26 of 30 (86.7%) with the PLA2 of A. mellifera and a purified preparation of PLA2. Twelve patients (40%) with severe anaphylaxis had IgE reactivity to a 39 kDa protein band of venom of both species, a third band, identified in immunoblot as hyaluronidase. The cross-reactivity of PLA2 and hyaluronidase of A. dorsata and A. mellifera were further confirmed by immunoblot inhibition results. Twenty five of 30 (83.3%) of our patients had positive venom specific IgE (>0.35 KUA/L) reactivity to Phadia ImmunoCAPs of A. mellifera venom. The observed IgE cross reactivity suggests the possibility of using A. mellifera venom as a diagnostic test for A. dorsata venom allergy.

Background The standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination. Methods Patients on methotrexate (10-20 mg/week) with a Disease Activity Score (DAS) > 3.2 were randomly assigned to rituximab (500 mg on days 1 and 15) or leflunomide (10-20 mg/day). The primary end-point was ACR20 at 24 weeks. Sample of 40 had 70% power to detect a 30% difference. ACR50, ACR70, DAS, EULAR good response, CD3 + (T cell), CD19 + (B cell) and CD19 + CD27+ (memory B cell) counts, tetanus and pneumococcal antibody levels were secondary end points. Results Baseline characteristics were comparable in the two groups. At week 24, ACR20 was 85% vs 84% (p = 0.93), ACR50 was 60% vs. 64% (p = 0.79) and ACR70 was 35% vs 32% (P = 0.84), in rituximab and in leflunomide groups respectively. Serious adverse events were similar. With rituximab there was significant reduction in B cells (p 0.05), T cells (P > 0.05) or tetanus antibody levels (P > 0.05). Conclusions Leflunomide-methotrexate combination is as efficacious as low-dose rituximab-methotrexate combination at 24 weeks, in RA patient’s refractory to initial DMARDs. The high responses seen in both groups have favorable cost implications for patients in developing countries. Changes in immune parameters with leflunomide are novel and need further characterization. Trial registration The trial was registered with the Sri Lanka Clinical Trials Registry (SLCTR), a publicly accessible primary registry linked to the registry network of the International Clinical Trials Registry Platform of the WHO (WHO-ICTRP) (registration number: SLCTR/2008/008 dated 16th May 2008).

Background Immediate type hypersensitivity to vaccines containing bovine/porcine excipients, such as the measles, mumps and rubella (MMR) vaccine is probably due to sensitization to bovine/porcine gelatin. Most patients with such reactions in Sri Lanka have cow's milk (CM) or beef allergy. Objectives We investigated whether those who had beef and CM allergy had a higher incidence of hypersensitivity reactions to vaccines and the possible trigger of such reactions. Material and methods Twenty patients with immediate type hypersensitivity reactions to vaccines containing bovine/porcine excipients, controls with allergy to beef/pork (n = 11) or CM (n = 11), and 8 non atopic controls were recruited. Total serum IgE, specific IgE to beef, CM, casein, beta lactoglobulin, gelatin and bovine serum albumin (BSA) by Phadia ImmunoCap and IgE to porcine gelatin by Western blot were evaluated. Results 11/20, 5/20, 2/20, 2/20, 1/20 and 1/20 patients reported allergic reactions to measles containing, JE, rabies primary chick embryo, pentavalent, diphtheria and tetanus, and adult diphtheria and tetanus vaccines, respectively. Only one patient with allergy to vaccines had gelatin specific IgE, whereas IgE to BSA was seen in 73.3%, 90%, 66.6% and 0 of vaccine, beef or CM allergic and non-atopic controls, respectively. The mean IgE to BSA was higher in patients with allergy to vaccines, although not significant. Specific IgE to BSA was present in 54.7% of children with allergy to CM, of whom 11.8% had high levels (>17.5 kUA/L). In contrast, 66.6% of these children did not have specific IgE to β-lactoglobulin, which is one of the major components of whey protein. Conclusion and clinical relevance Gelatin does not appear to play a major role in Sri Lankan children with allergy to vaccines. In contrast, due to the higher levels of BSA specific IgE, sensitization to BSA is possibly playing a role.

Background The aetiology of anaphylaxis differs according to types of foods consumed, fauna and foliage and cultural practices. Although the aetiology of anaphylaxis in Western countries are well known, the causes in South Asian countries have not been reported. We sought to determine the causes of anaphylaxis in patients referred to an immunology clinic in Colombo, Sri Lanka. Methods 238 episodes of anaphylaxis were reviewed in 188 patients who were referred and skin prick tests and in vitro tests (ImmunoCap) were carried out to assess the presence of allergen specific IgE. Clinical features and severity of anaphylaxis was also recorded along with treatment received. Results Anaphylaxis to food either following direct exposure 90/238 (37.5%) or after exercise in the form of food dependent exercise induced anaphylaxis 29/238 (12.2%) was the predominant cause of anaphylaxis. Allergy to cow’s milk and red meat, after immediate exposure, accounted for 66/238 (27.7%) of instances of all episodes of anaphylaxis and 66/90 (73.33%) of anaphylaxis due to food. Vaccines accounted for 28/238 (11.8%) of instances of anaphylaxis, especially among children. Of those who developed anaphylaxis to the MMR (n = 14), 71.4% of them had specific IgE to cow’s milk and 35.7% of them had specific IgE to beef. Of those who developed anaphylaxis to insect stings, 27/42 of these episodes occurred following stings of ants (family Formicidae). The predominant cause of anaphylaxis changed with the age, with food allergy being the most frequent trigger of anaphylaxis in childhood, while drug allergy and idiopathic anaphylaxis being more frequent after 30 years of age. Conclusions In this cohort, anaphylaxis to red meat appears to be the predominant cause of food induced anaphylaxis and presence of beef specific IgE and cow’s milk, appears to be a predisposing factor for vaccine induced anaphylaxis.

Background Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of the phagocytic cells, which results in absent or diminished levels of microbicidal reactive oxygen species. The disease occurs due to germline mutations in the genes encoding the five subunits of NADPH oxidase complex. The present study is a pilot study to understand the clinical and genetic aspects of CGD in Sri Lanka. Methods Clinical records of thirteen CGD patients were analysed and compared with similar studies performed in different countries and regions to identify patterns in demographics, clinical manifestations and infectious agents. Genomic DNA and cDNA were analysed in eight patients to identify mutations in CYBB and NCF1 genes, thereby to ascertain the potential X-linked and autosomal recessive (AR) CGD patients. Results The onset of symptoms in the patient cohort was very early (mean 4.6 months) compared to 20 months in India and 23.9 months in Latin America. Similarly, the age at diagnosis was lower (mean 1.6 years after birth) compared to other studies; 4.5 years in India and 6.1 years in Europe. Pulmonary manifestations were the most common (85%), followed by skin/subcutaneous infections (77%) and lymphadenopathy (62%). The death rate of local patients (38%) was higher than other countries (India 35%, Europe 20%). Majority (77%) were treated for tuberculosis at some point in life. Genetic analysis confirmed six out of eight patients as X-linked CGD cases with mutations in CYBB gene. A novel splice site mutation was identified in P-07 at position c.141+6 which resulted in the deletion of entire exon 2. Two siblings (P-05 and P-06) from consanguineous parents, were identified with AR-CGD based on the homozygous GT deletion mutation in NCF1 gene. Conclusions The clinical presentation, manifestations and genetic subtypes in the local cohort, appear to be comparable with global trends. Mycobacterial infections should be investigated and treated with more prominence. Effective treatment options are required to control the high mortality rate.

The aim of this study was to assess the inflammatory cytokine response and possible association with antimicrobial treatment with penicillin, ceftriaxone, and doxycycline in acute leptospirosis. In the early acute stage, interleukin-10 (IL-10) levels were higher in mild cases than in severe cases ( P = 0.01). IL-6 and IL-8 levels were low in patients who received >5 antimicrobial doses ( P < 0.01). IL-8 levels were negatively correlated with the number of ceftriaxone doses administered ( r = −0.315; P = 0.031). Further studies are needed to evaluate the possible downregulation of proinflammatory cytokines by ceftriaxone in leptospirosis.

Measurement of an individuals ability to respond to polysaccharide antigens is a crucial test to determine adaptive immunity. Currently the response to Pneumovax® is utilized but with the success of Prevnar®, measurement of the response to Pneumovax may be challenging. The aim of the study was to assess the response to Typhi Vi vaccination in both children and adult control groups and patients with primary immunodeficiency (PID). In the control groups, >95% of the individuals had pre Typhi Vi vaccination concentrations 94% achieving ≥3 fold increase in concentration (FI). The response to Typhi Vi vaccination was significantly lower in both children (p = 0.006) and adult (p = 0.002) PID groups when compared to their control groups. 11% and 55% of the children and adult PID groups respectively did not obtain a response >3FI. There were no significant differences between the responses obtained in the children and adult PID groups. When all individuals with PID were separated into those with either hypogammaglobulinemia (HYPO) or common variable immunodeficiency (CVID), both groups had a significantly lower median FI than the control group (19, 95%CI 5–56 vs 59, 95%CI 7–237; p = 0.01 and 1, 95%CI 1–56 vs 32, 95%CI 5–136; p = 0.005). Further, a >3FI differentiated the antibody responses between both the CVID and HYPO groups and their control groups (AUC: 0.83, 95%CI: 0.65–1.00, p = 0.005 and 0.81, 95% CI: 0.65–0.97, p = 0.01). The data suggests that measurement of the response to Typhi Vi vaccination could represent a complementary assay for the assessment of the response to a polysaccharide vaccine.

The aetiology of anaphylaxis ranges from food, insect venom, drugs and various chemicals. Some individuals do not develop anaphylaxis with the offending agent unless ingestion is related temporally to physical exertion, namely food dependent exercise induced anaphylaxis (FDEIA). The foods implicated are wheat, soya, peanut, milk and sea food. A retrospective study on patients with FDEIA from two Allergy clinics in Sri Lanka from 2011 to 2015 is reported. Patients were selected who fulfilled the following criteria: clinical diagnosis of anaphylaxis according to the World Allergy Organization (WAO) criteria, where the onset of symptoms was during exertion, within 4 h of ingesting a food, the ability to eat the implicated food independent of exercise, or exercise safely, if the food was not ingested in the preceding 4 h and an in vitro (ImmunoCap serum IgE to the food) or in vivo (skin prick test) test indicating evidence of sensitivity to the food. There were 19 patients (12 males: 7 females). The ages ranged from 9 to 45 (mean 22.9, median 19 years). Eight patients (42.1%) were in the 9–16 age group. Those below 16 years had a male:female ratio of 3:5, while for those above 16 years it was 9:2. Wheat was the only food implicated in FDEIA in all patients and was confirmed by skin prick testing, or by ImmunoCap specific IgE to wheat or ω − 5 gliadin. All patients had urticaria, while 5/19 (26.3%) had angioedema of the lips. Fifteen patients (78.9%) had shortness of breath or wheezing, while 8 (42.1%) had lost consciousness. Nine patients (47. 3%) had hypotension. Fourteen (73.6%) of our patients had severe reactions, with loss of consciousness or hypotension, while 5 (26.3%) had symptoms related to the gastrointestinal tract. One patient developed anaphylaxis on two occasions following inhalation of ganja, a local cannabis derivative along with the ingestion of wheat and exertion. Wheat is the main food implicated in FDEIA in Sri Lanka. A local cannabis derivative, ganja has been implicated as a cofactor for the first time.

Background The Global Polio Eradication Initiative, established in 1988, has made substantial progress toward achieving this target, with only 3 countries never having eliminated wild poliovirus. Persons with primary immune deficiency disorders (PIDD) exposed to OPV are at increased risk of vaccine-associated paralytic poliomyelitis (VAPP) and of prolonged excretion of Sabin polioviruses. However, the risk for prolonged excretion is not known. Therefore, we studied the prevalence of PIDD with long-term poliovirus excretion in Sri Lanka, a middle income country currently using OPV. Methods We stimulated the referral of patients under the age of 35 years, with clinical features suggestive of immune deficiency to the single immunology clinic in the country, where these patients were investigated for the presence of PIDD. Stool samples from patients with PIDD were cultured for the presence of poliovirus (PV). Poliovirus isolates were tested for intratypic differentiation (ITD). The VP1 region of all poliovirus isolates was sequenced. Results Of 942 patients investigated, 51 (5.4%) were diagnosed with PIDD. Five (10.2%) patients excreted poliovirus. A patient with X linked agammaglobulinemia (XLA) excreted a mixture of all three Sabin like (SL) poliovirus serotypes. One patient with severe combined immune deficiency (SCID) excreted SL type 2, and another with SCID excreted SL type 3. One patient with SCID excreted a P2 vaccine-derived poliovirus (VDPV 2), and another with common variable immune deficiency (CVID) excreted a VDPV 3. The 3 patients with SCID died before scheduled collection of subsequent samples one month later, while the patient with XLA had cleared the virus in stool sample collected after 3 and 11 months. The CVID patient with VDPV 3 excreted for 7 months, and has developed a 23 nucleotide divergence in VP1 (∼900 nucleotides) from the parental Sabin virus. Conclusions In our study, several patients with SCID, XLA and CVID excreted poliovirus. With improving health care quality patients with CVID and XLA may survive longer especially with provision of intravenous immune globulin. Regular screening of patients with PIDD for excretion of poliovirus is necessary to identify chronic excretors and make available specific therapies.

OBJECTIVES Primary immune deficiency is relatively rare. Patients present with recurrent or persistent infections or infections with opportunistic pathogens. We investigated patients who presented during the years 2005-7 with recurrent or persistent infections or infections with opportunistic organisms, for underlying immune deficiency. DESIGN Descriptive study. SETTING Department of Immunology, Medical Research Institute, Colombo. STUDY POPULATION 257 patients referred to the Department of Immunology, Medical Research Institute, Colombo, with a history of recurrent infections, for evaluation of possible immune deficiency. MEASUREMENTS Appropriate evaluation of immunological competence of the humoral and cell mediated immune systems. RESULTS There were 8 patients with agammaglobulinaemia (X linked agammaglobulinaemia and autosomal recessive agammaglobulinaemia), 2 patients each with ataxia telangiectasia, IgA deficiency and hyper-IgE syndrome, 3 patients with common variable immune deficiency (CVID), and 1 patient each with Griscelli syndrome, hyper-IgM syndrome and X linked severe combined immune deficiency (SCID). CONCLUSIONS Primary immune deficiency must be included in the evaluation of patients with recurrent infections, and timely intervention can prevent morbidity and mortality.

Hyper-IgE syndrome, a multi-system disorder affecting dentition, skeletal and immune systems and connective tissues, presents with recurrent infections and dermatitis. We report here the first case in Sri Lanka.

Vanadium is contained in fossil fuel such as coal, oil and sand oil and released in the air through the combustion. We studied the allergic and inflammatory potentials of vanadium as the factor of a recent increase of allergic disease. Vanadium oxide (V 2 O 5 ) and orthovanadate (Na 3 VO 4 ) released histamine from human basophils, rat mast cells and rat basophilic leukemia (RBL-2H3) cells in the presence of hydrogen peroxide (H 2 O 2 ). Activation of RBL-2H3 cells by vanadium/H 2 O 2 was accompanied by leukotriene synthesis, increases of [Ca 2+ ] i , multiple protein tyrosine phosphorylations and remarkable morphological changes. Pharmacological study suggests that vanadium/H 2 O 2 activates mast cells at the late phase, bypassing the early signaling components. Thus, vanadium can amplify the allergy in the presence of H 2 O 2 at the inflammation site in the global environment of industrial age.

Background While primary immunodeficiencies (PID has been recognized in the west for decades, recognition has been delayed in the third world. This study attempts to detail the spectrum of PID, the therapy provided, and constraints in the diagnosis and treatment in a middle income country such as Sri Lanka. Methods Nine hundred and forty two patients with recurrent infections and features suggestive of immune deficiency, referred from the entire country in a 4 year period, to the sole immunology unit in Sri Lanka were included. The following tests were performed. Full blood counts, serum Immunoglobulin and complement C3 and C4 levels, functional antibody levels, enumeration of lymphocyte subsets, in vitro and in vivo T cell functional assays,, nitroblue tetrazolium assay to diagnose chronic granulomatous disease, hair shaft assay to diagnose Griscelli syndrome. Sequencing of the common gamma chain to identify x linked severe combined immune deficiency, and X linked agammaglobulinemia was confirmed by assaying for Btk mutations by single sequence conformation polymorphism. HIV/AIDS was excluded in all patients. Results Seventy three patients were diagnosed with a primary immune deficiency. The majority (60.27%) had antibody deficiency. Common variable immune deficiency was the commonest (28.76%), followed by X linked agammaglobulinemia (XLA) (20.54%). Five patients had possible hyper IgM syndrome. Ten patients had severe combined immune deficiency (SCID), including 2 with x linked SCID, in addition to DiGeorge syndrome (2), ataxia telangiectasia (6), autosomal dominant hyper IgE syndrome (2), chronic granulomatous disease (4), leucocyte adhesion deficiency type 1 (2) and Griscelli syndrome (3). Patients with autoinflammatory, innate immune and complement defects could not be identified due to lack of facilities. Conclusions Antibody deficiency is the commonest PID, as in the west.IgA deficiency is rare. Autoinflammatory diseases, innate immune and complement deficiencies could not be identified due to lack of diagnostic facilities. Lack of awareness of PID among adult physicians result in delay in treatment of adult patients. While treatment of antibody deficiencies provided in state hospitals has extended life expectancy, there is no treatment available for severe T cell defects.