Hereditary angio-oedema in the Western Cape Province, South Africa.

BACKGROUND: Hereditary angio-oedema (HAE) is an autosomal dominant condition caused by a deficiency in the C1-esterase inhibitor protein, resulting in increased bradykinin release. It presents clinically with recurrent attacks of angio-oedema, commonly affecting the limbs, face, upper airway and gastrointestinal tract. Little is known about this condition in sub-Saharan Africa. OBJECTIVES: To analyse and report on the clinical presentation and treatment of patients with HAE in the Western Cape Province, South Africa. METHODS: A retrospective analysis was conducted on a series of 60 cases of HAE seen between 2010 and 2015 at the Allergy Diagnostic and Clinical Research Unit, University of Cape Town Lung Institute, and the Allergy Clinic at Groote Schuur Hospital, Cape Town. The findings in 43 cases of type 1 HAE are described. Parameters assessed included age, gender, age of diagnosis, duration of illness, family history, identifiable triggers, average duration of attack, number of attacks per year and type of attack. RESULTS: A total of 43 patients were included in this study. Of these, 65.1% (28/43) were female. The median age at diagnosis was 20 years (interquartile range (IQR) 10 - 27) and the median duration of illness 10.5 years (IQR 6 - 22). Of the patients, 62.8% (27/43), 32.6% (14/43) and 4.7% (2/43) were of mixed ancestry, white and black African, respectively; 51.2% (22/43) were index cases, with the remaining 48.8% (21/43) diagnoses via family member screening, 12 families making up the majority of the cohort. The mean (standard deviation) duration of an acute attack was 49 (25.8) hours, and 64.3% (27/42), 71.4% (30/42), 14.3% (6/42) and 88.1% (37/42) of patients experienced facial or upper airway, abdominal, external genitalia and limb attacks, respectively. Danazol for long-term prophylaxis was used in 21 patients, while C1-inhibitor concentrate (Berinert) was accessed for short-term prophylaxis in only four patients. Acute life-threating attacks were treated with fresh frozen plasma in 11 patients, and only four accessed icatibant. The mortality rate for the period 2010 - 2015 was 4.5% (2/43). The prevalence of HAE in the Western Cape was estimated to be 1:140 000. CONCLUSIONS: HAE occurs in South Africans of all ethnicities, and life-threatening attacks occur in almost two-thirds of patients. Despite limited therapeutic options and very limited access to gold-standard therapies available in the developed world, our mortality rate is very low, with both the deaths related to inability to access emergency treatment rapidly.

Hereditary angio-oedema in the Western Cape Province, South Africa

Background. Hereditary angio-oedema (HAE) is an autosomal dominant condition caused by a deficiency in the C1-esterase inhibitor protein, resulting in increased bradykinin release. It presents clinically with recurrent attacks of angio-oedema, commonly affecting the limbs, face, upper airway and gastrointestinal tract. Little is known about this condition in sub-Saharan Africa.Objectives. To analyse and report on the clinical presentation and treatment of patients with HAE in the Western Cape Province, South Africa.Methods. A retrospective analysis was conducted on a series of 60 cases of HAE seen between 2010 and 2015 at the Allergy Diagnostic and Clinical Research Unit, University of Cape Town Lung Institute, and the Allergy Clinic at Groote Schuur Hospital, Cape Town. The findings in 43 cases of type 1 HAE are described.Parameters assessed included age, gender, age of diagnosis, duration of illness, family history, identifiable triggers, average duration of attack, number of attacks per year and type of attack.Results. A total of 43 patients were included in this study. Of these, 65.1% (28/43) were female. The median age at diagnosis was 20 years (interquartile range (IQR) 10 - 27) and the median duration of illness 10.5 years (IQR 6 - 22). Of the patients, 62.8% (27/43), 32.6% (14/43) and 4.7% (2/43) were of mixed ancestry, white and black African, respectively; 51.2% (22/43) were index cases, with the remaining 48.8% (21/43) diagnoses via family member screening, 12 families making up the majority of the cohort. The mean (standard deviation) duration of an acute attack was 49 (25.8) hours, and 64.3% (27/42), 71.4% (30/42), 14.3% (6/42) and 88.1% (37/42) of patients experienced facial or upper airway, abdominal, external genitalia and limb attacks, respectively.Danazol for long-term prophylaxis was used in 21 patients, while C1-inhibitor concentrate (Berinert) was accessed for short-term prophylaxis in only four patients. Acute life-threating attacks were treated with fresh frozen plasma in 11 patients, and only four accessed icatibant. The mortality rate for the period 2010 - 2015 was 4.5% (2/43). The prevalence of HAE in the Western Cape was estimated to be 1:140 000.Conclusions.HAE occurs in South Africans of all ethnicities, and life-threatening attacks occur in almost two-thirds of patients. Despite limited therapeutic options and very limited access to gold-standard therapies available in the developed world, our mortality rate is very low, with both the deaths related to inability to access emergency treatment rapidly

Quality of life and control of allergic rhinitis in patients from regions beyond western Europe and the United States.

There is comparatively little information on health-related quality of life (HRQoL) in subjects with allergic rhinitis (AR) or allergic rhinoconjunctivitis (AR/C) in countries beyond western Europe and North America. The primary aim of this investigation was therefore to review and assess the information in the public domain on HRQoL in AR/C patients from diverse regions of the world, represented by different countries, including Argentina, Australia, Brazil, Russia, Singapore, South Africa and Turkey. Second, in view of the absence of a standardized definition for 'AR control', the review aimed to determine whether a working definition of AR/C can be inferred from validated tests or other instruments documented to date. Despite the comparatively low number of studies, this review demonstrated that overall the symptoms of AR/C impair the HRQoL of patients in these regions by adversely impacting sleep, daily activities, physical and mental status and social functioning, similar to that demonstrated in much larger numbers of studies of AR/C patients in Europe and the United States. Furthermore, the findings of the review suggest that 'overall' control of the disease should encompass reduction of nasal and ocular symptoms, as well as improvements in HRQoL, comorbid conditions and cognition. Although some instruments are currently available for measuring control of AR, none are capable of assessing all these aspects, emphasizing the need to develop appropriate new instruments.

Complete deficiency of the sixth complement component (C6Q0), susceptibility to Neisseria meningitidis infections and analysis of the frequencies of C6Q0 gene defects in South Africans.

Complete complement component 6 deficiency (C6Q0) is a co-dominant genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis infections. Affected individuals have two affected alleles which can be homozygous or compound heterozygous for the particular gene defects they carry. This disorder has been diagnosed relatively frequently in Western Cape South Africans. Affected patients are prescribed penicillin prophylaxis. In 2004 we commenced a clinical follow-up study of 46 patients. Of these, 43 had family age-matched C6 sufficient controls. Participants were classified as either (i) well, or (ii) having a serious illness (SI) or died (D). An SI was a long-term illness that did not allow the performance of normal daily activities. Among 43 patients, 21 were well and 22 were SI/D, while among 43 matched controls, 35 were well and eight were SI/D. This difference is highly significant. Among all 46 C6Q0 patients, those who had had recurrent infection had significantly more SI/D than those who had suffered none or one infection. Thus, this work demonstrates the long-term serious outcome of repeated meningococcal disease (MD) episodes. We investigated the frequencies of four C6Q0 pathogenic mutations known to affect Cape patients (828delG, 1138delC, 821delA and 1879delG) in 2250 newborns. A total of 103 defective alleles (2·28%) and three affected C6Q0 individuals were detected. For all defects combined, 5·24 affected subjects (C6Q0) are expected among 10,000 individuals. What is still unknown is the number of C6Q0 individuals who suffer MD or other infectious diseases.

Prevalence and diversity of allergic rhinitis in regions of the world beyond Europe and North America.

BACKGROUND: There is comparatively little information in the public domain on the diversity in prevalence and triggers/factors associated with allergic rhinitis (AR) or allergic rhinoconjunctivitis (AR/C) in countries beyond western-Europe and North America. OBJECTIVE: To review the prevalence and the sensitizing agents/triggers and factors associated with AR/C in several countries in Africa, the Asia-Pacific region, Australia, Eastern Europe, Latin America, Middle East and Turkey. METHODS: Articles published in English in peer-reviewed journals were assessed and selected for further review, following an extensive literature search using the Medline database. RESULTS: This review demonstrated that prevalence of AR and AR/C in these regions has predominantly been investigated in children; with studies indicating wide inter- and intra-regional variations ranging from 2.9% AR and 3.8% AR/C in 10-18-years-old children from one region in Turkey to 54.1% AR and 39.2% AR/C in 13-14-years-old children in one region in Nigeria. Moreover, the prevalence of AR and AR/C has increased markedly over the last decade particularly in some of the more affluent African countries, China-Taiwan and several Middle East countries, likely as a consequence of improved living standards leading to increased exposure to multiple traditional and non-traditional sensitizing agents and risk factors similar to those noted in western-Europe and North America. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest that the greater diversity in prevalence of AR or AR/C in populations in these regions is in contrast to the lower diversity of AR or AR/C in the 'western populations (USA and Europe), which tend to be more uniform. This review provides a comprehensive database of the important allergens and triggers which are likely to influence the prevalence of allergic rhinitis in these diverse regions, where the prevalence of allergic rhinitis is increasing and its adverse impact on the quality of life of affected individuals is increasingly recognised.

Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patients.

BACKGROUND: Nonsedating H(1)-antihistamines are recommended for the treatment of urticaria by the recent EAACI/GA(2)LEN/EDF guidelines. The aim of this study was to compare the efficacy, after 4 weeks of treatment, with levocetirizine 5 mg and desloratadine 5 mg, both once daily in the morning, in symptomatic chronic idiopathic urticaria (CIU) patients. METHODS: This multi-center, randomized, double-blind study involved 886 patients (438 on levocetirizine and 448 on desloratadine). The primary objective was to compare their efficacy on the mean pruritus severity score after 1 week of treatment. Mean pruritus severity score over 4 weeks and pruritus duration score, number and size of wheals, mean CIU composite score (sum of the scores for pruritus severity and numbers of wheals), quality of life, and the patient's and investigator's global satisfaction with treatment, were secondary efficacy measures. RESULTS: Levocetirizine led to a significantly greater decrease in pruritus severity than desloratadine over the first treatment week; mean pruritus severity scores of 1.02 and 1.18 for levocetirizine and desloratadine, respectively (P < 0.001). The result was similar for the entire 4-week treatment period (P = 0.004). In addition, levocetirizine decreased pruritus duration and the mean CIU composite scores to a significantly greater extent than desloratadine during the first week (P = 0.002 and 0.005, respectively) and over the entire study (P = 0.009 and P < 0.05, respectively). Similarly, levocetirizine increased the patients' global satisfaction after one and 4 weeks (P = 0.012 and 0.021, respectively), compared with desloratadine. Safety and tolerability were similar in both groups. CONCLUSIONS: Levocetirizine 5 mg was significantly more efficacious than desloratadine 5 mg in the treatment of CIU symptoms.

Guideline for the management of chronic asthma in children--2009 update.

OBJECTIVE: To revise the guideline for the diagnosis and management of chronic asthma in children in view of the following considerations: the existing South African Childhood Asthma Working Group (SACAWG) guideline was produced 10 years ago; diagnosis of asthma in young children remains a challenge; evidence-based treatment is the new paradigm; new treatment approaches to achieving and maintaining control; therapeutic roles of several medications have evolved; more studies and data on treatment in young children; new medications and formulations; a change of emphasis in assessing asthma control to guide treatment changes. The main aim of the guideline is to promote a better standard of treatment based on understanding of the pathophysiology and pharmacotherapy of asthma, and encouraging uniformity in asthma management. EVIDENCE: A detailed literature review by a working group of clinicians from relevant disciplines. The strategies recommended are classified according to the evidence category in Appendix B, and denoted as Evidence A, B, C and D. RECOMMENDATIONS: These include an appropriate diagnostic approach, environmental control measures, treatment options, definition of asthma control, and strategies to achieve control. ENDORSEMENT: The guideline document was endorsed by the South African Thoracic Society (SATS), the National Asthma Education Programme (NAEP), the South African Paediatric Association (SAPA) and the South African Academy of Family Practice.

Mycobacterium tuberculosis infection may protect against allergy in a tuberculosis endemic area.

BACKGROUND: Epidemiological studies have shown an inverse relation of mycobacterial infection and the frequency of allergic diseases and asthma. Recent evidence suggests that allergic inflammation may be inhibited in the presence of chronic and persistent infections, such as that by Mycobacterium tuberculosis (MTB). The relation of tuberculin skin test (TST) size, an accepted marker of MTB infection and the frequency of allergic disease symptoms has not been reported from an area where MTB infection is endemic. OBJECTIVE: To investigate the association of TST and allergic disease symptoms, in children living in a tuberculosis (TB) endemic area. METHODS: In this cross-sectional study, 841 children aged 6-14 years from randomly selected household addresses in two poor communities of Cape Town, South Africa, were investigated with TST and standardized International Study on Asthma and Allergies in Childhood-based questionnaire on allergic disease symptoms. RESULTS: Children with positive TST (> or =10 mm) were significantly less likely to have allergic disease symptoms, in particular allergic rhinitis (AR) (adjusted odds ratio 0.43; 95% confidence interval 0.24-0.79) than those with negative TST. This association remained significant after adjusting for possible confounders and correcting for the effect of clustering (>1 child per household address) in the sample. There was a significant inverse linear trend in the relation of TST size in millimetre and the frequency of allergic disease symptoms, in particular AR (P<0.001). CONCLUSIONS: These results of inverse association of strong TST reaction and allergic disease symptoms in children from a TB endemic area are in support of the hypotheses that allergic inflammation may be inhibited by chronic infections, such as MTB.

Inverse association between Mycobacterium tuberculosis infection and atopic rhinitis in children.

BACKGROUND: The association between Mycobacterium tuberculosis (MTB) infection and atopy remains controversial. AIM: To investigate the association between MTB infection and atopic rhinitis in children living in a high TB incidence area. METHODS: In this cross-sectional study 418 children aged 6-14 years from an established epidemiological research-site in a poor urban community were invited to participate. They were assessed for allergic rhinitis (ISAAC questionnaire) and skin responses to tuberculin and eight environmental allergens. The presence of a BCG scar was documented, intestinal parasites and total and Ascaris lumbricoides-specific IgE levels were measured. Atopic rhinitis was defined, using the new World Allergy Organization (WAO) definition, as reported allergic rhinitis and a positive skin prick test (SPT > or =3 mm) to any allergen. RESULTS: Among the 337 children enrolled 10.4% had allergic rhinitis, 17.5% a positive SPT and 53% a positive tuberculin skin test (TST > or =10 mm). Children with a positive TST were significantly less likely to have recent atopic rhinitis (OR(adjusted) 0.06; 95% CI 0.007-0.5) than those with a negative TST. SPTs were significantly more common in children with negative TST who had recent allergic rhinitis (OR(adj) 34.0; 95% CI 7.6-152.6), but not in children with positive TST and recent allergic rhinitis (OR(adj) 0.6; 95% CI 0.07-5.2). CONCLUSIONS: MTB infection seems to reduce the prevalence of atopic rhinitis, and influences SPT reactivity in children with allergic rhinitis from a high TB incidence area.

Occupational allergy in laboratory workers caused by the African migratory grasshopper Locusta migratoria.

BACKGROUND: Recent reports of fatal asthma cases associated with swarms of locusts affecting African countries have highlighted the importance of this insect in causing asthma morbidity and mortality. However, only limited information is available about the allergic health outcomes such as asthma and its determinants in exposed individuals. In this study, workers exposed to the African migratory locust Locusta migratoria were evaluated for allergic health outcomes as well as the nature of the offending allergens. METHODS: Ten scientists and technicians exposed to locusts in a laboratory were investigated for locust-related allergy using questionnaires and immunological tests. The presence of allergy was determined by quantification of specific IgE and IgG to L. migratoria using the UniCAP system and via skin-prick testing (SPT). The allergens were characterized by Western blot and ImmunoCAP inhibition assays. RESULTS: Six of the 10 workers experienced symptoms ranging from urticaria and rhinoconjuctivitis to asthma. Seven individuals demonstrated sensitivity on SPT and five had specific IgE antibodies to L. migratoria. Significant cross-reactivity was demonstrated for allergens in the locust faeces, body and wings but not to cockroach allergens. Novel allergens with molecular weights of approximately 70 kDa were identified in locust wings, which are distinctly different from other known allergen sources from locusts. CONCLUSION: Exposure to L. migratoria allergens is a potential sensitizer in exposed individuals. Raised levels of locust-specific IgE can be readily quantified. The wings of this insect species have been identified as a novel allergen source.

Effect of betamethasone-loratadine combination therapy on severe exacerbations of allergic rhinitis : a randomised, controlled trial.

OBJECTIVE: Corticosteroids are effective in controlling the inflammatory component of allergic rhinitis; however, evidence for the clinical efficacy of systemic corticosteroids in this disease is sparse. It is further common practice to combine oral corticosteroids with antihistamines in the treatment of acute exacerbations of allergic rhinitis. The aim of this study was to investigate the effect of low-dose oral betamethasone alone and in combination with loratadine in a group of patients with allergic rhinitis with clinically significant obstruction. METHODS: In this parallel, double-blind, active controlled multicentre study, 299 patients with severe allergic rhinitis were randomly allocated to either betamethasone 1.0mg or betamethasone 1.0mg plus loratadine 10mg or betamethasone 0.5mg plus loratadine 10mg or loratadine 10mg alone for 5-7 days. Total symptom scores, nasal obstruction, and doctor and patient perception of improvement were measured as markers of disease severity. RESULTS: Although not statistically significant, both betamethasone 1.0mg regimens resulted in a total symptom score difference of at least 1 or more from loratadine (i.e. mean [SD] change in total symptom score of 4.10 [3.10] and 4.40 [3.62] vs 3.10 [3.30], respectively, for betamethasone 1.0 mg plus loratadine, betamethasone 1.0 mg and loratadine). All corticosteroid-containing regimens were significantly better than loratadine alone with regard to the patients' (p < 0.013) and doctors' (p < 0.009) perceptions of improvement. They significantly favoured loratadine in combination with betamethasone over single-drug therapy (i.e. odds ratio: investigator ratings 0.49, 0.36 and 0.45, and patient ratings 0.47, 0.40 and 0.43, respectively, for 0.5 mg and 1.0 mg betamethasone plus loratadine and betamethasone 1.0 mg alone vs loratadine alone). Betamethasone 1.0mg plus loratadine also resulted in significant reduction of the relapse rate compared with the other therapies. CONCLUSIONS: This study demonstrated the benefit of a short course of a systemic low dosage of corticosteroids with and without antihistamine therapy during acute severe exacerbations of allergic rhinitis. Combination treatment with betamethasone 1.0mg and loratadine 10mg was significantly better in relieving symptoms of hayfever as experienced by patients. This was the first study to give evidence of benefit of systemic low-dose corticosteroids with and without an antihistamine in patients with acute exacerbations of allergic rhinitis.

Effects of triamcinolone on quality of life in patients with persistent allergic rhinitis.

OBJECTIVE: To study the effects of triamcinolone acetonide on health-related quality of life (HRQL) in adult patients with allergic rhinitis. METHODS: This study was conducted in South Africa as a placebo-controlled, multicenter, randomized, double-blind study. Following a 7-day baseline run-in, patients were treated for 28 days with either triamcinolone or placebo. Interviewer-assisted quality-of-life assessments were conducted using the Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Total symptom scores, including nasal congestion, were measured using daily diary cards. RESULTS: A total of 337 patients were recruited and 253 patients completed the study per protocol, of which 55 had seasonal allergic rhinitis (SAR) and 198 had persistent allergic rhinitis (PAR). Improvements in the mean scores per area of the RQLQ were significantly better with triamcinolone compared with placebo for the entire study group for activities (P = .04 at visit 4) and sleep, nasal symptoms, emotional problems, and overall score (P = .002, P = .04, P = .03, and P = .04, respectively, at visit 3). When the patients with SAR were separated from the patients with PAR in the analysis, improvement with triamcinolone was better than placebo only in the PAR patients. The overall investigator and patient assessments of relief favored triamcinolone. CONCLUSIONS: Triamcinolone given for 4 weeks improves symptom scores and HRQL in patients with allergic rhinitis. The ability of triamcinolone to relieve nasal congestion symptoms in PAR patients was correlated with improvements in HRQL.

Levocetirizine is effective for symptom relief including nasal congestion in adolescent and adult (PAR) sensitized to house dust mites.

BACKGROUND: Antihistamines are the most commonly prescribed class of medication for perennial allergic rhinitis (PAR). The primary objective of this study was to determine whether levocetirizine (Xyzal(R)), the active enantiomer of cetirizine, could achieve at least a 50% improvement in PAR symptoms compared to the placebo over the first week of treatment. METHODS: A total of 294 patients with PAR due to house dust mites were randomized in this 8-week double-blind, placebo-controlled, multicentre trial to receive either levocetirizine 5 mg/day or placebo. Mean Total Four-Symptom Scores (T4SS) (nasal pruritus, ocular pruritus, rhinorrhoea and sneezing) were compared between treatment groups over weeks 1, 4 and 6. All individual symptom scores, including nasal congestion, were also studied. RESULTS: Levocetirizine showed an 86% improvement in T4SS over the first week of treatment and a 47% improvement over the entire treatment period compared with placebo. Absolute changes from baseline were 3.64 and 2.47 for levocetirizine and placebo, respectively. Individual symptom scores showed statistically significant (P < or = 0.01) differences in favour of levocetirizine for all study time-points. Nasal congestion was unexpectedly significantly improved (P < 0.001). The incidence of reported adverse events was comparable between treatment and placebo group. CONCLUSIONS: Levocetirizine 5 mg/day is an effective and well-tolerated treatment of PAR. In addition, levocetirizine is effective for the relief of nasal congestion.