Capturing total steroid burden in patients with atopic dermatitis and asthma.

Background: The cumulative burden of cutaneous, inhaled, intranasal and systemic corticosteroids (CS) in individual patients should be routinely assessed. Methods: Our monitoring tool collected data on CS type, potency, frequency, side effects, interventions and patient counseling in every encounter. Results: 82 AD patients had 151 encounters. Severe AD had more side effects than those without (68.18% vs 41.67% respectively, P < 0.0333). Those with higher TSB had more side effects overall (p < 0.0493). There was also significant positive correlation with higher TSB and the overall number of side effects (p < 0.0116). 101 asthmatics had 193 encounters. Over 50% of asthma patients had other CS. Severe asthmatics had more side effects than those without (62.5% vs 20.8%, p < 0.0001). Patients with higher TSB had more side effects overall (p < 0.0001). There was also significant positive correlation with a higher TSB and the overall number of side effects (p < 0.0001). 80% of AD and 90% of asthma patients were satisfied with the counseling. The EHR in AD and asthma resulted in counseling in 89% and 93% respectively and real-time intervention in 27.8% and 3% respectively. Although patients with side effects had more dose adjustments, those without side effects also warranted adjustments. Physician surveys demonstrated improved satisfaction with the EHR tool over time, and minimal impact on visit time. Conclusion: The utilization of our EHR monitoring tool allows for the identification and tracking of TSB in patients, associated side effects and leads to real-time physician intervention.

A 64-year-old man with chronic obstructive pulmonary disease and an atypical rash.

A 64-year-old male patient with a 15-year history of chronic obstructive pulmonary disease presented with an atypical rash that was refractory to standard therapy. Pulmonary function tests confirmed an obstructive lung disease. Basic laboratory workup revealed conflicting information, leading to a diagnostic challenge discussed in this article. Ultimately, careful testing did reveal the diagnosis and the patient was treated accordingly.

Response to ecallantide treatment of acute attacks of hereditary angioedema based on time to intervention: results from the EDEMA clinical trials.

Hereditary Angioedema (HAE) is a rare, debilitating, genetic disorder characterized by acute attacks of edema without urticaria. Ecallantide, a direct plasma kallikrein inhibitor, is approved for treatment of acute HAE attacks. This article addresses the efficacy of ecallantide in the treatment of moderate-to-severe attacks of HAE based on time to treatment. A post hoc integrated analysis of the EDEMA4 and EDEMA3-DB clinical trials was performed based on the time to patient's treatment, defined as the time from initial recognition of moderate-to-severe symptoms to dosing (cohort, 0-2, >2-4, >4-6, >6-8, and >8 hours). Mean symptom complex severity (MSCS) score and treatment outcome score (TOS) were analyzed. Complete or near-complete resolution of symptoms was assessed at 4 and 24 hours. In this analysis, 70 patients received 30 mg of subcutaneous (s.c.) ecallantide and 73 patients received placebo. Change from baseline in MSCS score and TOS at 4 hours revealed significantly better response to ecallantide versus placebo for patients treated >2-4 (n = 46; p = 0.002; p = 0.003) or >4-6 (n = 47; p = 0.044; p = 0.043) hours after symptom onset. Fewer patients were treated within 2 hours of symptom onset; for these patients (n = 10; p = 0.752; p = 0.422) treatment did not achieve statistical significance. For overall response, complete or near-complete resolution was greatest within the 0- to 2-hour cohort (71.4%). As with other therapies for HAE early ecallantide therapy is optimal. Treatment with ecallantide within 6 hours of symptom onset leads to more rapid and sustained improvement of symptoms.

A challenging diagnosis of alpha-1-antitrypsin deficiency: identification of a patient with a novel F/Null phenotype.

Alpha-1-antitrypsin (A1AT) deficiency is a genetic disease characterized by low levels and/or function of A1AT protein. A1AT deficiency can result in the development of COPD, liver disease, and certain skin conditions. The disease can be diagnosed by demonstrating a low level of A1AT protein and genotype screening for S and Z mutations, which are the most common. However, there are many genetic variants in A1AT deficiency, and this screening may miss rarer cases, such as those caused by dysfunctional protein. We identified a patient with a previously unreported F/null phenotype that was missed by routine screening. This case highlights the wide variation in possible mutations, limitations in diagnostics, and the importance of combining clinical suspicion with measurement of protein levels, phenotypic analysis, and in appropriate cases expanded genetic analysis.

Occupational Contact Dermatitis: An Update.

Occupation contact dermatitis (CD) is a common inflammatory skin condition impacting every professional industry in the United States. It is associated with significant personal and professional distress, loss of revenue, and decreased productivity. Occupational CD is further subdivided into irritant CD and allergic CD. Frequently, workers may suffer from a combination of both types. Numerous workplace exposures are implicated, but there are several themes across professions, such as CD related to frequent handwashing and wet work. A detailed occupational history, physical examination, and patch testing can help to make the diagnosis. Treatment includes identification of the substance and avoidance, which often is quite challenging.

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.

Recruitment of mammalian cell fibronectin to the surface of Chlamydia trachomatis.

Pathogenic bacteria exploit the presence of various host cell molecules in order to colonize new tissues. Fibronectin is involved in a wide range of cell functions in vivo, and staphylococci, streptococci, and gonococci have evolved mechanisms to utilize this glycoprotein to mediate host cell binding. We show that elementary bodies (EB) from two biovars of Chlamydia trachomatis recruit fibronectin to their surfaces upon lysis of the host cell. We also demonstrate that a heparan sulfate lyase-sensitive molecule on chlamydial EB is responsible for binding at least a portion of this fibronectin.