Sujoy Khan

Clinical profile of patients with C1-inhibitor deficiency from Eastern India

C1-inhibtor deficiency or hereditary angioedema is a rare, autosomal dominant disorder that is characterized by severe episodic attacks of angioedema that can affect any part of the body. It is caused by mutations in the C1-inhibitor gene (C1-INH or SERPING 1 gene) that is mapped to chromosome 11 (11q12-q13.1). The majority of patients have a family history although 25% of cases can be de novo mutations (i.e., no family history). Distinguishing the angioedema due to C1-inhibitor deficiency from allergic or idiopathic angioedema requires clinical acumen, and this delay in diagnosis leads to unnecessary surgical interventions, and in unfortunate cases, mortality that is now possible to prevent with easy access to screening tests and proper management.

Does immunoglobulin therapy have a role in treating Dengue virus infection with induced systemic capillary leak syndrome

The report of severe cardiovascular changes in the eight children with secondary dengue infection and dengue shock syndrome (DSS) by Kositseth et al. [1] was consistent with systemic capillary leak syndrome (SCLS). It is thought to be distinct from classical dengue fever (DF). However, clinicians working in endemic areas need to be aware that such textbook presentations may not be applicable in this age when extremes of climate and increase in air travel have complicated the infection demographics in clinical medicine. A report published in March 2012, showed the high prevalence of SCLS among travelers, a third of which were primary dengue cases and 85% also had classical DF [2]. It is interesting to hypothesize that patients co-infected with two serotypes of dengue virus (DENV) may develop multiple organ failure and DSS, but no specific reports on these complications are available from Asia (DENV-2/-3 and DENV-3/-4), or the Americas (DENV-2/-3 and DENV-3/-4). Whether complications from multiple organ failure and DSS was the case in the recent epidemic of dengue virus related deaths in children and adults from Eastern India during the rainy season/autumn 2012 remains to be proven [3]. As with most infectious pathogens, homologous DENV genetic recombination events have been widely reported [4,5], but fortunately, there have not been any reports of heterologous DENV-serotype recombination events. Such events would result in new chimeric strains and the immunological hypothesis of antibodyenhanced disease and multi-organ failure would be the most likely explanation [6]. Does high-dose intravenous immunoglobulin (hdIVIG) sourced from the local donor population, rather than imported, offer a viable treatment option in DENV-related SCLS? A publication from the European Registry of patients with idiopathic SCLS showed improvement after treatment with hdIVIG [7]. Treatment with hdIVIG certainly remains a feasible option with viral-related autoimmune manifestations such as Kawasaki disease, but will this treatment prove effective against the dreaded thrombocytopenia and SCLS in DENV infection? [8,9] Only a multi-center clinical trial can answer this question. In the interim time, civic and health authorities must work together with entomology and virology centers to prevent unnecessary deaths from this vector-borne disease.

Persistent cow's milk allergy with attacks of anaphylaxis

The most common food protein causing allergy in infants and young children is cow′s milk, but persistence of this allergy into adulthood is rare. It is estimated that 2-3% of the general population suffers from cow′s milk allergy (CMA), but reports of anaphylaxis in adulthood are limited. This case report discusses persistence of CMA with several anaphylaxis episodes in a 12-year-old girl who had allergic reactions from 6 months of age. She is also unable to tolerate milk from all available animal sources including goat and sheep. Skin prick test was strongly positive at 10 mm at 7 years of age, with specific IgE cow′s milk >100 kUA/L when she presented with anaphylaxis episodes 5 years later. Patient-specific management plans need to be in place to avoid and manage anaphylaxis, especially for patients who do not have easy access to healthcare.

Antiphospholipid syndrome is an important modifiable risk factor of stroke in the young

Dengue infection presenting first as encephalitis is rare. Research suggests that direct invasion of the nervous system by dengue virus is possible.[1] The other possible mechanism is infiltration of virus-infected macrophages into the brain.[1,2] The clinical symptomatology which includes altered level of consciousness, seizures, headache, meningeal signs, and pyramidal tract signs are nonspecific. Laboratory diagnosis of dengue encephalitis is based upon detection of either the virus itself or viral antigen NS1, or the dengue-specific IgM antibody, in the CSF. Viral cultures are generally difficult, and hence, serology is commonly used for laboratory diagnosis. MRI reveals the focal involvement of brain parenchyma, thus suggesting encephalitis rather than encephalopathy as the underlying etiology. In addition, MRI can be useful in differentiating between viral infections of central nervous system, as some viral encephalitides display a tropism for certain brain structures resulting in characteristic imaging features.[3] There are no characteristic MRI features of dengue encephalitis. Some studies describe involvement of globus pallidus, temporal lobes, thalamus, hippocampus, pons, and spinal cord on MRI.[4-6] The symmetrical hyperintense signal in bilateral parietooccipital regions on FLAIR and T2W sequences as seen in our patient has not been described earlier. Bilateral symmetrical parietooccipital involvement on MRI is typically seen in posterior reversible encephalopathy syndrome (PRES), which is a clinicoradiologic entity occurring as a result of failure of the posterior circulation to autoregulate in response to acute changes in blood pressure. The clinical manifestations of PRES overlap with that of encephalitis. However, its usual association with acute hypertension, and the frequent involvement of cortical as well as subcortical regionon MRI are the differentiating features of PRES. The complete clinical recovery in our patient is consistent with good prognosis for most cases of dengue encephalitis as described in literature.[2] Chandrashekhar A. Sohoni

Raised immunoglobulin E levels are not predictive of allergic reactions to blood products

144 Asian Journal of Transfusion Science Vol 8, Issue 2, July December 2014 supported by new onset rash, increasing vasopressor requirement and rapid shock reversal after adrenaline and lastly raised total IgE also. Subsequently, soybean allergy was confi rmed by history and skin test. According to Naranjo probability scale method of adverse drug reaction, this case is possible type (Naranjo total score >8).[3]

Helicobacter Pylori Associated Urticarias

I read with interest the article by Takashi Yoshimasu and Fukumi Furukawa on eradication therapy for Helicobacter pylori associated urticaria1 and entirely agree that future guidelines on urticaria should highlight this issue with an aim to formulate separate management strategy for these patients. In fact, our last published guidelines on chronic urticaria discuss the importance of this infection in both acute and chronic (episodic) urticarias.2 Active surveillance for detection of H pylori is one of the strategies I have adopted in my practice given the high incidence of this infection and gastric cancer in this region (H pylori seroprevalence rates in Bangladesh 92%, Kuwait 84% and India at 79%).3 I would therefore like to share my experience of H pylori associated urticaria from my clinic in eastern India. Of 25 dyspeptic patients screened for H pylori with upper GI endoscopy over last year, 6 (5 males, 1 female) were found to be positive for rapid urease test at endoscopy (mean age 42.2 years, range 29-54 years). The duration of urticaria (spontaneous, pressure and solar) ranged from 1-6 years and all patients were on multiple antihistamines including ebastine and montelukast (leukotriene receptor antagonist) at various time points and never achieved complete remission (CR, i.e., always required to be on anti-histamines). Two patients were positive for anti-thyroid peroxidase antibodies, while one had prostatomegaly. All improved symptomatically and achieved CR within 3 months after receiving H pylori eradication therapy (pantoprazole 40 mg, amoxicillin 750 mg, clarithromycin 500 mg for 14 days) and combination of fexofenadine 180 mg with hydroxyzine 25-50 mg. In contrast, 6 children (aged 7-15 years) with chronic episodic urticaria screened for the presence of H pylori IgG antibodies using ELISA were negative, and improved on pantoprazole and fexofenadine over 6 months. It is important that clinicians recognize that H pylori not only pose a substantial burden in terms of gastric cancer, but also in some patients with chronic ‘ idiopathic’ urticaria where directed investigations and treatment may prove beneficial.

Ocular manifestations of the antineutrophil cytoplasmic antibody and antiphospholipid syndromes

Sir, n nI read with interest the article by Kumar Saurabh and colleagues on the patient profile of retinal vasculitis from Eastern India,[1] and would like to comment on the importance of a more comprehensive laboratory work-up to ensure that the vasculitides syndromes associated with significant morbidity and mortality are not missed. The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and antiphospholipid antibody syndrome (APS) both can initially present with only ocular manifestations such as uveitis and work-up to exclude these vasculitides is more important in younger patients without known systemic risk factors.[2,3] n nThe AAVs include Wegeners granulomatosis (cytoplasmic staining pattern seen on immunofluorescence of ethanol-fixed human neutrophils, cANCA, with specificity for proteinase 3 [PR3]) while microscopic polyangiitis and Churg–Strauss syndrome (usually have a perinuclear pattern on immunofluorescence, pANCA, with specificity for myeloperoxidase [MPO]) can present with various ophthalmic manifestations. But in a subset of patients, these findings may be the earliest indicators of systemic disease (up to 50% in children).[2,4] Orbital and anterior segment findings are most common, whereas posterior segment complications such as retinal vasculitis and optic neuropathy occur much less frequently. However, a study on patients with pANCA-associated vasculitis reported that ocular surface (scleritis and peripheral keratitis) and posterior segment manifestations (central or branch retinal vein occlusion, optic neuropathy, acute posterior multifocal placoid pigment epitheliopathy) were the important eye presentations.[5] However, a significant proportion of patients will have systemic symptoms, but may not initially present, and the finding of abnormal chest X ray or serum creatinine or glomerulonephritis should warrant an urgent laboratory request to exclude an ANCA-associated vasculitis. n nThe autoimmune disease APS is characterized by the consistent presence of antiphospholipid antibodies (or anticardiolipin or anti-β2GPI antibodies) at 12 weeks, arterial or venous thromboses and repetitive foetal loss. Diluted Russel viper venom time (dRVTT) is often used as one of the phospholipid-dependent tests that shows a prolonged APTT which gets corrected only with increased phospholipid concentrations (suggesting the presence of lupus anticoagulant). This can be present without ds-DNA antibodies with a nonspecific positive antinuclear antibody (ANA) only, and hence the addition of lupus anticoagulant in the diagnostic criteria of systemic lupus erythematosus. Ocular involvement in APS occurs in 8-88% of patients, of which 75% with ocular presentation were women with mean age at 40 years.[3] Ocular findings in APS include anterior uveitis, unilateral or bilateral blurring of vision, transient scotoma, uniteral amaurosis fugax (bilateral suggests CNS ischemia), visual field defects and various retinal pathologies (hemorrhages, vasculitis, retinopathy) discussed by Utz VM and Tang J in their review.[3] n nClinicians should therefore have a high index of suspicion of AAV and APS, in especially younger patients, which would be the first step in avoiding the inevitable complications of arterial inflammation and visual loss. Emphasis to lower additional risks of thrombosis such as treating cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, tobacco use or obesity), during immobilization or malignancy, treating microalbuminuria, screening for inherited thrombophilias, and counseling regarding oral contraceptive use remain equally important.