Novel systemic drugs in treatment of atopic dermatitis: results from phase II and phase III studies published in 2017/2018

Purpose of review The present review will give an update of recently published clinical studies on novel systemic treatment approaches in atopic dermatitis. Recent findings Until 2017 immunosuppressive drugs such as cyclosporine had to be used in atopic dermatitis when the disease could not sufficiently be treated with topical drugs. Several new substances specifically targeting inflammation in atopic dermatitis are currently studied. In 2017, dupilumab was approved in the United States and in Europe for first-line biologic treatment of moderate to severe atopic dermatitis in adults. The antibody blocks a subunit of the interleukin (IL)-4 and IL-13 receptor, thus inhibiting effects of two key cytokines in type 2 polarized inflammation. In addition to the studies on dupilumab recent clinical investigations on the effects on anti-IL-13 (lebrikizumab, tralokinumab), anti-IL-31 receptor (nemolizumab), anti-IL-22 (fezakinumab), and on small molecules targeting the histamine-4-receptor (ZPL389) and the Janus kinase inhibitor baricitinib have been published as full papers in the last 2 years. Summary A couple of promising novel therapeutical targets have recently been investigated and published in clinical trials on atopic dermatitis. Correspondence to Thomas Werfel, Abteilung Immundermatologie und experimentelle Allergologie, Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, 30625 Hannover, Deutschland. Tel: +49 5115325092; fax: +49 5115328112; E-mail: werfel.thomas@mh-hannover.de Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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High Resolution Computed Tomography of Temporal Bone: The Predictive Value in Atticoantral Disease

Abstract

To evaluate predictive value of high resolution computed tomography in atticoantral disease. We conducted a prospective observational study in 49 patients suffering from atticoantral disease at tertiary referral institute. Preoperatively, all the patients underwent unenhanced high resolution computed tomography (HRCT) of temporal bone parallel to orbitomeatal line by using multislice scanner. We evaluated presence of soft tissue attenuation, ossicular erosion, facial canal erosion, dural exposure, erosion of semicircular canal, labyrinthine fistula, erosion of scutum and tegmen tympani in CT scan. HRCT is recommended in atticoantral disease with complications. This study demonstrates the predictive value of HRCT of temporal bone as a diagnostic modality in atticoantral disease. HRCT shows 100% sensitivity (Sn) of soft tissue density detected in middle ear, aditus and attic. Specificity (Sp) was more for eustechian tube area and sinus tympani. Ossicular erosions of malleus (Sn = 90.9%, Sp = 75%), incus (Sn = 93.2%, Sp = 80%), stapes (Sn = 78.8%, Sp = 68.8%) were detected. Erosion of scutum (Sn = 94.1%, Sp = 80%), tegmen (Sn = 66.7%, Sp = 100%), sinus plate (Sn = 100%, Sp = 97.9%), facial nerve canal (Sn = 75%, Sp = 100%), semicircular canal fistula (Sn = 80%, Sp = 97.7%) and cochlear promontory fistula (Sn = 50%, Sp = 97.9%) were evaluated. HRCT temporal bone helps to evaluate disease extent and involvement of surrounding structures. Hence it helps in deciding surgical approach and also prevents impending complications.

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Maffucci Syndrome with Clival Enchondroma in Nasopharynx: A Case Report

Abstract

Maffucci syndrome is an extremely rare sporadic disease, characterized by multiple enchondromas and associated with multiple hemangiomas and/or lymphangiomas. First case was reported in 1881, and fewer than 200 case have been reported to date. Potential sarcomatous malignant transformation have been noticed in previous cases. This report describes the case of 21 years-old male complain of right sided nasal obstruction for 10 months, and right sided aural fullness. Examination revealed multiple asymptomatic nodules in both hands since childhood, that have not been investigated and a large nasopharyngeal mass. Computed tomography, showed a 36 mm in 30 mm diameter lesion extending from the inferior aspect of the clivus and basisphenoid into the nasopharynx, which did not seems to be highly vascular with angiogram. Incidental radiological findings of multiple bubbly lytic bony lesions. Endoscopic sinus surgery and clival lesion excision was performed. Pathology confirmed diagnosis of clival enchondroma with clinical and radiological features consistent with Maffucci syndrome. Clear etiology have not been established yet. Mutations in gene encoding parathyroid hormone receptor 1 found in 10% of enchondromatosis. Mutations in gene encoding isocitrate dehydrogenase 1 and 2 (IDH 1&2) occur in some enchondromas and spindle cell hemangiomas. Maffucci syndrome usually presents with asymmetrical distribution of multiple enchondromas. Malignant transformation is the most concerning potential sequel. Many studies have shown sarcomatous degeneration of enchondromas to chondrosarcomas in average of 25% of cases. Patient counselling and education are crucial in the management. Surgical excision usually for symptomatic patients and suspicious lesions. Nevertheless, all patient of Maffucci syndrome will require a long term follow up and surveillance for the lifelong risk of malignant transformation. Maffucci syndrome diagnosis based on clinical presentation, radiological and histopathological findings. Surgical excision offered for symptomatic patients and for suspicious lesions. Lifelong risk of sarcomatous malignant transformation necessitate a long term surveillance.

https://ift.tt/2OXV4ub

High Resolution Computed Tomography of Temporal Bone: The Predictive Value in Atticoantral Disease

Abstract

To evaluate predictive value of high resolution computed tomography in atticoantral disease. We conducted a prospective observational study in 49 patients suffering from atticoantral disease at tertiary referral institute. Preoperatively, all the patients underwent unenhanced high resolution computed tomography (HRCT) of temporal bone parallel to orbitomeatal line by using multislice scanner. We evaluated presence of soft tissue attenuation, ossicular erosion, facial canal erosion, dural exposure, erosion of semicircular canal, labyrinthine fistula, erosion of scutum and tegmen tympani in CT scan. HRCT is recommended in atticoantral disease with complications. This study demonstrates the predictive value of HRCT of temporal bone as a diagnostic modality in atticoantral disease. HRCT shows 100% sensitivity (Sn) of soft tissue density detected in middle ear, aditus and attic. Specificity (Sp) was more for eustechian tube area and sinus tympani. Ossicular erosions of malleus (Sn = 90.9%, Sp = 75%), incus (Sn = 93.2%, Sp = 80%), stapes (Sn = 78.8%, Sp = 68.8%) were detected. Erosion of scutum (Sn = 94.1%, Sp = 80%), tegmen (Sn = 66.7%, Sp = 100%), sinus plate (Sn = 100%, Sp = 97.9%), facial nerve canal (Sn = 75%, Sp = 100%), semicircular canal fistula (Sn = 80%, Sp = 97.7%) and cochlear promontory fistula (Sn = 50%, Sp = 97.9%) were evaluated. HRCT temporal bone helps to evaluate disease extent and involvement of surrounding structures. Hence it helps in deciding surgical approach and also prevents impending complications.

https://ift.tt/2ATUlXY

Maffucci Syndrome with Clival Enchondroma in Nasopharynx: A Case Report

Abstract

Maffucci syndrome is an extremely rare sporadic disease, characterized by multiple enchondromas and associated with multiple hemangiomas and/or lymphangiomas. First case was reported in 1881, and fewer than 200 case have been reported to date. Potential sarcomatous malignant transformation have been noticed in previous cases. This report describes the case of 21 years-old male complain of right sided nasal obstruction for 10 months, and right sided aural fullness. Examination revealed multiple asymptomatic nodules in both hands since childhood, that have not been investigated and a large nasopharyngeal mass. Computed tomography, showed a 36 mm in 30 mm diameter lesion extending from the inferior aspect of the clivus and basisphenoid into the nasopharynx, which did not seems to be highly vascular with angiogram. Incidental radiological findings of multiple bubbly lytic bony lesions. Endoscopic sinus surgery and clival lesion excision was performed. Pathology confirmed diagnosis of clival enchondroma with clinical and radiological features consistent with Maffucci syndrome. Clear etiology have not been established yet. Mutations in gene encoding parathyroid hormone receptor 1 found in 10% of enchondromatosis. Mutations in gene encoding isocitrate dehydrogenase 1 and 2 (IDH 1&2) occur in some enchondromas and spindle cell hemangiomas. Maffucci syndrome usually presents with asymmetrical distribution of multiple enchondromas. Malignant transformation is the most concerning potential sequel. Many studies have shown sarcomatous degeneration of enchondromas to chondrosarcomas in average of 25% of cases. Patient counselling and education are crucial in the management. Surgical excision usually for symptomatic patients and suspicious lesions. Nevertheless, all patient of Maffucci syndrome will require a long term follow up and surveillance for the lifelong risk of malignant transformation. Maffucci syndrome diagnosis based on clinical presentation, radiological and histopathological findings. Surgical excision offered for symptomatic patients and for suspicious lesions. Lifelong risk of sarcomatous malignant transformation necessitate a long term surveillance.

https://ift.tt/2OXV4ub

MyD88 signaling in T regulatory cells by endogenous ligands dampens skin inflammation in filaggrin deficient mice

Publication date: Available online 9 August 2018

Source: Clinical Immunology

Author(s): Sabine Hoff, Michiko K. Oyoshi, Jason L. Hornick, Raif S. Geha, NIH/NIAID funded Atopic Dermatitis Research Network

Abstract

Mutations in filaggrin are associated with atopic dermatitis. Filaggrin-deficient flaky tail (Flg^ft/ft) mice develop spontaneous inflammatory skin lesion that wax and wane. We show that loss of MyD88 promotes the persistence of skin lesions in Flg^ft/ft mice and exaggerates their expression of the Th17-associated cytokines Il7a and Il22. The development and persistence of skin lesions in Flg^ft/ft mice was independent of the microbiota. MyD88-mediated signals are shown to be important for the accumulation of T regulatory cells (Tregs) in lesional skin of Flg^ft/ft mice. Adoptive transfer of WT Tregs dampened the severity of skin lesions in MyD88^−/−/Flg^ft/ft mice. These results suggest that MyD88 signaling in Treg cells by endogenous ligands attenuates skin inflammation in filaggrin deficiency.

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Post-traumatic thrombotic microangiopathy following pelvic fracture treated with transcatheter arterial embolization: a case report

Thrombotic microangiopathy is caused by various conditions, but few cases secondary to trauma have been reported. We present the rare case of a patient with thrombotic microangiopathy-induced high-impact traum...

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