Successful use of lanadelumab in an elderly patient with type II hereditary angioedema

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurring episodes of subcutaneous and/or submucosal edema without urticaria due to an excess of bradykinin (1, 2). HAE is classified into 2 main types (1). Type I HAE is caused by deficiency of C1 esterase inhibitor, accounting for 85% of cases (1). Type II HAE occurs in only 15% of cases and is marked by normal to elevated levels of C1 esterase inhibitor but with a reduction in activity (1). An angioedema attack can range in severity depending on the location and degree of edema (2). Furthermore, patients with HAE are often diagnosed with anxiety and depression secondary to their poor quality of life (3). Thus, long-term prophylaxis of attacks can be crucial to reduce the physical and psychological implications. For long-term prophylaxis, lanadelumab, a subcutaneously delivered monoclonal antibody inhibitor of plasma kallikrein, has been proven to decrease the frequency of HAE attacks without significant side effects (4). However, data is limited, specifically regarding patients with type II HAE and patients >/= 65 years (4).

Poisoning by Megathyrsus maximus (Sin. Panicum maximum) cv. Colonião in horses in the state of Rio de Janeiro

ABSTRACT: Colic outbreaks in horses have been associated with the grazing of several Megathyrsus maximus (Sin. Panicum maximum) cultivars in the North and Central-West regions of Brazil. In this paper, we report a horse colic outbreak in the Southeast region of Brazil caused by ingestion of the “Colonião” cultivar of M. maximus, which has not previously been considered as toxic. The five affected horses belonged to the Veterinary Platoon based at the Central Ammunition Deposit of the Brazilian Army in the city of Paracambi, Rio de Janeiro state, Brazil. The horses had access to treated water and commercial concentrate, and were located in a field of M. maximus at the time of the outbreak. All horses exhibited clinical signs of colic and bloat, and three of them died. The extend of the clinical course ranged from four to five days in the three animals that died; in the two animals that recovered from the colic episodes, the extend of the clinical courses were 10 and 15 days. Necropsy findings revealed intestinal and gastric bloating and hemorrhages involving the intestinal wall. Light microscopy showed moderate diffuse lymphoplasmacytic and eosinophilic enteritis with multifocal erosions, in addition to submucosal edema associated with multifocal vasculitis. The pathogenesis of colic caused by M. maximus ingestion in horses has not yet been elucidated. Some authors have suggested that higher starch concentrations in M. maximus during the rainy season may be responsible for the toxicity of this plant. However, the findings of this study do not support this hypothesis. As a prophylactic measure, it is suggested that horses do not graze exclusively M. maximus at the beginning of rainy periods, in which regrowth of this grass occurs. In Brazil, outbreaks of horse colic associated with ingestion of varieties of Megathyrsus can also occur outside the North and Midwest regions, under specific climate conditions.

Intestinal atresia: histopathologist view

Background: Intestinal atresia forms one of a common cause for intestinal obstruction in neonates. There is a debate about its pathogenesis and many theories have been suggested. Studies regarding its clinical and histomorphological features are less in Indian literature. The present study aimed to determine the clinical and histomorphological features of cases of intestinal atresia.Methods: Thirty-nine cases of intestinal atresia were studied both retrospectively (twenty-six) and prospectively (thirteen) over a period of two years. Their clinical and histomorphological features were studied.Results: Intestinal obstruction was most common clinical diagnosis. Type II atresia was most common. Ileal atresia was highest in number. Associated congenital anomalies noted were situs inversus with splenunculi, patent vitelo-intestinal duct, duplication cyst, Meckel’s diverticulum, ileocecal web, duodenal web and omphalocele. Histological features such as inspissated meconium, calcification, ulceration, fibrosis, thick-walled vessels, edema were noted.Conclusions: Findings such as mucosal edema, congestion, ulceration, submucosal edema, thick-walled blood vessels, fibrosis, hemorrhage, transmural ischemia, calcification, suggest that an intra vascular accident may be responsible for origin of the atresia.

Clinical presentation of hereditary angioedema

Hereditary angioedema (HAE) is a rare, autosomal dominant disease caused by a deficiency in the C1-inhibitor protein. It is characterized by recurrent episodes of nonpruritic, nonpitting, subcutaneous or submucosal edema that typically involves the extremities or the gastrointestinal tract. However, the genitourinary tract, face, oropharynx, and/or larynx may be affected as well. Symptoms often begin in childhood, worsen at puberty, and persist throughout life, with unpredictable severity. Patients who are untreated may have frequent attacks, with intervals that can range from every few days to rare episodes. Minor trauma and stress are frequent precipitants of swelling episodes, but many attacks occur without clear triggers. HAE attacks may be preceded by a prodrome and/or be accompanied by erythema marginatum. The swelling typically worsens over the first 24 hours, before gradually subsiding over the subsequent 48 to 72 hours. Although oropharyngeal swelling is less frequent, more than half of patients have had at least one episode of laryngeal angioedema during their lifetime. Attacks may start in one location and spread to another before resolving. HAE attacks that involve the abdomen or oropharynx have been associated with significant morbidity and mortality. Abdominal attacks can cause severe abdominal pain, nausea, and vomiting. Bowel sounds are often diminished or silent, and guarding and rebound tenderness may be present on physical examination. These findings may lead to unnecessary abdominal imaging and procedures. Fluid shifts into the interstitial space or peritoneal cavity can cause clinically significant hypotension. Laryngeal edema poses the greatest risk for patients with HAE. Although prompt diagnosis and treatment improves outcomes, the variable presentation of HAE can make it difficult to diagnose.

Subglottic Cryotherapy: A Pilot Study in New Zealand White Rabbits

To describe proof of concept and pilot data for a cryotherapy application in the subglottis in a rabbit airway model. Four New Zealand white rabbits (3 experimental, 1 control) underwent general anesthesia and laryngoscopy and bronchoscopy. Experimental animals had cryotherapy applied with a direct contact 1.9-mm cryoprobe. Animals were euthanized at days 0, 2, and 6 posttreatment. Histologic changes were assessed in the treated subglottic tissues. This preliminary work has demonstrated that, with early cryogenic injury in the subglottis, there is mild mucosal epithelial injury associated with submucosal edema, acute inflammatory infiltrate, and degeneration of venule endothelial cells. Mucosal epithelial repair and resolution of the inflammatory response appear to be relatively rapid. We hope that this may provide a foundation to further explore cryotherapy as a primary or adjuvant treatment option for pediatric subglottis stenosis.

Acute Hereditary Angioedema With Airway Compromise: Avoiding Airway Intervention With C1 Inhibitor Concentrate

Introduction: Hereditary angioedema (HAE) is an autosomal dominant disease caused by deficiency of the plasma protein C1 inhibitor (C1-INH). Patients classically present with recurrent localized subcutaneous or submucosal edema lasting for 2 to 5 days, severe abdominal pain, or acute airway obstruction which can be fatal. Case presentations: We highlight 2 patients with acute airway compromise secondary to HAE who were successfully treated with plasma-derived C1-INH concentrates. Conclusions: The timely administration of plasma-derived C1-INH concentrates for the acute treatment of HAE has been proven to be effective in both patients in aborting an airway complication. A high index of suspicion is required for the early diagnosis and treatment of this potentially fatal condition.

Bacterial Ulcerative Esophagitis in an Immunocompetent Patient

Bacterial esophagitis is a very rare condition usually occurring in patients with immunosuppression. To our best knowledge, bacterial esophagitis without underlying immunosuppressive disease has not been reported. We report an immunocompetent patient with bacterial esophagitis caused by B-hemolytic Streptococcus which resulted in an esophageal stricture. A 68-year-old female was admitted for odynophagia which had developed several days before. Upper endoscopy revealed extensive ulceration covered by whitish exudates with submucosal edema at the proximal esophagus. She was treated with steroids and empirical broad-spectrum antibiotics. Within 14 days the symptoms improved. Since growth of B-hemolytic Streptococcus was detected in nasal smear culture, bacterial esophagitis was suspected. Gram staining was carried out on the already obtained tissue that had been fixed with formalin. There was heavy infiltration with gram-positive cocci morphologically consistent with Streptococcus. Since the bacterial colony was demonstrated histologically, the diagnosis of bacterial esophagitis caused by B-hemolytic Streptococcus was confirmed. In addition, complete resolution of the inflammation following antibiotics therapy was further evidence of the bacterial cause of the esophagitis.

Rectal Ischemia Mimicked Tumor Mass

Ischemic proctitis is a rare disease which is usually encountered in elderly with comorbidities. We present a case of an 80-year old man with severe coronary disease who presented with severe hematochezia and hypotension. Endoscopy revealed a rectal mass 3-4 cm above the dental line and rectosigmoid mucosal inflammation compatible with ischemic colitis. The rectal insult was so intense that it resembled a neoplasmatic lesion. We discuss the causes, the prognostic factors, and the clinical and therapeutic challenges of this rare, albeit life-threatening entity, and we review the relative literature. A percentage of 10%–20% of patients with ischemic colitis usually have a distal potentially obstructing lesion or disorder such as cancer, diverticulitis or fecal impaction. Ischemic colitis, when mucosal and submucosal edema is severe and hemorrhagic nodules are large enough, can mimic a neoplasmatic lesion. The best treatment approach is a conservative management initially with a close clinical followup and after stabilization a repetition of rectal endoscopy with new biopsies. Early recognition of this clinical entity is of paramount importance to implement appropriate therapy (conservative or surgical) and avoid potentially fatal treatment of presumed inflammatory or infectious bowel diseases.

Ecallantide for the Treatment of Hereditary Angiodema in Adults

Hereditary angioedema (HAE) is a clinical disorder characterized by a deficiency of C1 esterase inhibitor (C1-INH). HAE has traditionally been divided into two subtypes. Unique among the inherited deficiencies of the complement system, HAE Types I and II are inherited as an autosomal dominant disorder. The generation of an HAE attack is caused by the depletion and/or consumption of C1-inhibitor manifested as subcutaneous or submucosal edema of the upper airway, face, extremities, or gastrointestinal tract mediated by bradykinin. Attacks can be severe and potentially life-threatening, particularly with laryngeal involvement and treatment of acute attacks in the United States has been severely limited. In December 2009 the FDA approved ecallantide for the treatment of acute HAE attacks. Ecallantide is a small recombinant protein acting as a potent, specific and reversible inhibitor of plasma kallikrein which binds to plasma kallikrein blocking its binding site, directly inhibiting the conversion of high molecular weight kininogen to bradykinin. Administered subcutaneously, ecallantide was demonstrated in two clinical trials, EDEMA3 and EDEMA4, to decrease the length and severity of acute HAE attacks. Although there is a small risk for anaphylaxis, which limits home administration, ecallantide is a novel, safe, effective and alternative treatment for acute HAE attacks.