Leptin Enhances Hepatic Fibrosis and Inflammation in a Mouse Model of Cholestasis.

Leptin is an adipokine with roles in food intake and energy metabolism through its actions on neurons in the hypothalamus. The role of leptin in obesity and cardiovascular disorders is well documented. However, its influence on liver conditions such as cholestasis is poorly understood. The effects of exogenous leptin and leptin-neutralizing antibody on biliary hyperplasia, hepatic fibrosis, and inflammation in the multidrug resistance protein 2 knockout (Mdr2KO) mouse model of cholestasis were assessed by quantifying markers specific for cholangiocytes, activated hepatic stellate cells (HSCs), and cytokines. Serum and hepatic leptin were increased in Mdr2KO mice compared with FVB/NJ (FVBN) controls, and exogenous leptin enhanced biliary hyperplasia and liver fibrosis in Mdr2KO and FVBN mice. Leptin administration increased hepatic expression of C-C motif chemokine ligand 2 and IL-6 in Mdr2KO mice. In contrast, leptin-neutralizing antibody reduced intrahepatic bile duct mass and decreased HSC activation in Mdr2KO mice compared with FVBN controls. Sex-related differences were noted, with female Mdr2KO mice having more leptin than males. In cholangiocytes and LX2 cells in vitro, leptin increased phosphorylated Akt and stimulated cell proliferation. Leptin receptor siRNA and inhibitors of Akt phosphorylation impaired leptin-induced cell proliferation and proinflammatory cytokines. The current data suggest that leptin is abnormally increased in cholestatic mice, and excess leptin increases ductular reaction, hepatic fibrosis, and inflammation via leptin receptor-mediated phosphorylation of Akt in cholangiocytes and HSCs.

Correction to: Successful Minimally Invasive Management of a Gastroduodenal Artery Pseudoaneurysm Causing Extrinsic Bile Duct Compression.

[This corrects the article on p. e00663 in vol. 8, PMID: 34646903.].

Successful Minimally Invasive Management of a Gastroduodenal Artery Pseudoaneurysm Causing Extrinsic Bile Duct Compression.

Gastroduodenal artery (GDA) pseudoaneurysms are rare clinical entities that typically develop in the setting of chronic inflammation of the pancreas, although idiopathic pseudoaneurysms can occur. Although GDA pseudoaneurysms carry the risk of rupture with resultant hemorrhage, they seldom are reported to cause biliary obstruction. We report a unique case of biliary obstruction secondary to extrinsic compression of the bile duct by a GDA pseudoaneurysm successfully managed by nonoperative means.

Imported fire ant field reaction and immunotherapy safety characteristics: the IFACS study.

BACKGROUND: Imported fire ants (IFAs) are endemic in the southeastern United States, including Texas; can sting multiple times; and are a well-known cause of anaphylaxis. There are few data available on how many stings typically lead to systemic reactions (SRs). Likewise, there are no reports currently in the literature that characterize the safety of IFA subcutaneous immunotherapy (SCIT). OBJECTIVE: We sought to analyze a case-cohort sample of patients for IFA SCIT risk factors and to characterize the index field reactions of these patients. METHODS: A case-cohort study based on a 3-year retrospective chart review (2005-2008) at a single institution was performed for patients receiving IFA SCIT. Field reactions leading to initiation of IFA SCIT were also reviewed. RESULTS: Seventy-seven patients (40 female patients; mean age, 34 years) received 1,887 injections, and 7 patients experienced 8 SRs, for a rate of 0.4% per injection and 9.1% per patient. SRs were mild. Having an SR to skin testing was associated with increased odds of having an SR to IFA SCIT (odds ratio, 4.75; 95% CI, 1.13-20.0), as were large local reactions (odds ratio, 34.5; 95% CI, 6.52-182). No other risk factors were identified. Of the index field reactions leading to IFA SCIT, 59% were the result of 1 sting, and 87% of subjects experienced only 1 SR before initiation of IFA SCIT. Two of 4 patients who experienced loss of consciousness during the index field reaction required an increased maintenance dose for optimal response. CONCLUSIONS: IFA SCIT is safe; however, having an SR to skin testing or the presence of large local reactions increases the odds of having an SR to IFA SCIT. The majority of SRs to IFA field stings resulted from 1 sting.

Antibiotics for the allergist: part 2.

OBJECTIVE: To review antibiotic use and selection for disorders commonly seen in allergy practice. DATA SOURCES: MEDLINE searches were performed cross-referencing antibiotic, antimicrobial, management, and treatment with multiple disorders commonly seen in allergy practice. References of the chosen articles were also examined. STUDY SELECTION: Articles were selected based on their relevance to the subject matter. RESULTS: A large body of research is available relevant to both conventional and novel uses of antibiotics. The use of antibiotics is in question for some disorders, whereas novel approaches to therapy with macrolide antibiotics are areas of active investigation. Meanwhile, patterns of microbial resistance continue to evolve. CONCLUSION: For decades, antibiotics have been traditional first-line treatment for many disorders. Currently, this paradigm appears to be shifting as periods of observation come into favor and nonbacterial causes of inflammation are under greater scrutiny. Nonetheless, appropriate antibiotic selection often remains a key element in the treatment of these disorders. Knowledge of the relevant microbiology is an inherent requirement in selecting antibiotic therapies and necessitates awareness of current trends in bacterial resistance.

Transient dermatographism presenting within the first 18 hours after birth in an otherwise healthy newborn.

We present the first reported instance of transient dermatographism occurring within 18 hours after birth in an otherwise healthy term newborn. The infant's dermatographism resolved without intervention or sequelae, and this report provides guidance for the clinician to follow when presented with similar presentations.

Antibiotics for the allergist: part 1.

OBJECTIVE: To review antibiotic use and selection for disorders commonly seen in allergy practice. DATA SOURCES: MEDLINE searches were performed cross-referencing the keywords antibiotic, antimicrobial, management, and treatment with multiple disorders commonly seen in allergy practice. References of the chosen articles were also examined. STUDY SELECTION: Articles were selected based on their relevance to the subject matter. RESULTS: A large body of research is available that is relevant to both conventional and novel uses of antibiotics. The use of antibiotics is in question for some disorders, whereas novel approaches to therapy with macrolide antibiotics are areas of active investigation. Meanwhile, patterns of microbial resistance continue to evolve. CONCLUSION: For decades, antibiotics have been traditional first-line treatments for many disorders. Recently, this paradigm appears to be shifting as periods of observation come into favor and nonbacterial causes of inflammation are under greater scrutiny. Nonetheless, appropriate antibiotic selection often remains a key element in the treatment of these disorders. Knowledge of the relevant microbiology is an inherent requirement in selecting antibiotic therapies and necessitates awareness of current trends in bacterial resistance.

Pruritus, papules, and perspiration.

BACKGROUND: The development of pruritus and papules with increased body temperature is a common clinical scenario seen in allergy practice, often leading to a diagnosis of cholinergic urticaria. OBJECTIVE: To describe an unusual case of miliaria and its significance in the evaluation of patients with pruritic papular eruptions that occur with increased body temperature. METHODS: An 18-year-old woman was referred to a local allergist for the evaluation of cholinergic urticaria. For the preceding 6 months, she had experienced a facial burning sensation along with diffuse pruritus accompanied by water-filled pinpoint bumps on her abdomen and extremities during exercise and with hot tub use. The lesions appeared anytime she exercised, and she reduced her workouts because of the associated discomfort. An exercise challenge was performed given the atypical description of her cutaneous symptoms. RESULTS: After indoor aerobic exercise on a treadmill, physical examination revealed facial flushing and numerous pinpoint translucent vesicles covering her abdomen. The diagnosis of miliaria crystallina was made. Given the intense pruritus she experienced with the lesions, she was prescribed cetirizine, 10 mg once daily. However, she noted no improvement with her exercise-induced miliaria. At follow-up 1 year later, her miliaria symptoms had spontaneously resolved with no sequelae observed. CONCLUSION: Intermittent, pruritic, papular eruptions that occur with perspiration can provide a diagnostic challenge when not present on initial examination. Although this presentation often leads to a diagnosis of cholinergic urticaria, our case illustrates that other disorders must be considered in the differential diagnosis. In these situations, exercise challenge is a valuable adjunct.

Severe refractory cholinergic urticaria treated with danazol.

BACKGROUND: Cholinergic urticaria is a form of physical urticaria triggered by a rise in core body temperature. Antihistamines are the mainstay of treatment; however, adequate symptom control can sometimes be difficult to maintain. Limited data suggest danazol may be an effective alternative in severe, refractory cases. METHODS AND RESULTS: We present a case of a 22-year-old male with severe, refractory cholinergic urticaria. Despite treatment with high doses of antihistamines, he continued to have symptoms that impaired his ability to function. Treatment with danazol resulted in a significant improvement in the control of his urticaria. DISCUSSION: Cholinergic urticaria can sometimes be severe. In cases that fail to respond to traditional forms of treatment, danazol is a viable alternative for the treatment of cholinergic urticaria. Given the potential adverse effects associated with its use, danazol should be reserved for more severe and refractory cases.

Cold urticaria: a case report and review of the literature.

Cold urticaria represents a form of physical urticaria. The disorder is uncommon, and patients with the condition are at risk for systemic reactions and thus must be identified, counseled, and treated accordingly. Diagnosis principally is clinical and is confirmed by the results of cold stimulation tests such as placing an ice cube on the patient's forearm. Treatment primarily consists of preventive counseling, epinephrine autoinjections, and antihistamines. We present the case of a 9-year-old girl with acquired cold urticaria and review the literature.