More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations.

BACKGROUND: Infant death in keratitis-ichthyosis-deafness (KID) syndrome is recognized; its association with specific genotypes and pathophysiology is inadequately understood. OBJECTIVE: We sought to discover characteristics that account for poor outcomes in lethal KID syndrome. METHODS: We collected 4 new cases and 9 previously reported, genotyped cases of lethal KID syndrome. We performed new molecular modeling of the lethal mutants GJB2 p.A88V and GJB2 p.G45E. RESULTS: Infant death occurred in all patients with GJB2 p.G45E and p.A88V; it is unusual with other GJB2 mutations. Early death with those 2 "lethal" mutations is likely multifactorial: during life all had ≥1 serious infection; most had poor weight gain and severe respiratory difficulties; many had additional anatomic abnormalities. Structural modeling of GJB2 p.G45E identified no impact on the salt bridge previously predicted to account for abnormal central carbon dioxide sensing of GJB2 p.A88V. LIMITATIONS: This clinical review was retrospective. CONCLUSION: GJB2 p.G45E and p.A88V are the only KID syndrome mutations associated with uniform early lethality. Those electrophysiologically severe mutations in GJB2 reveal abnormalities in many organs in lethal KID syndrome. All patients with KID syndrome may have subtle abnormalities beyond the eyes, ears, and skin. Early genotyping of KID syndrome births will inform prognostic discussion.

Rituximab combined with conventional therapy versus conventional therapy alone for the treatment of mucous membrane pemphigoid (MMP).

BACKGROUND: The use of rituximab for refractory autoimmune blistering diseases is increasing. Data related to rituximab for the treatment of mucous membrane pemphigoid (MMP) are limited. OBJECTIVE: We sought to compare the efficacy of adding rituximab with traditional immunosuppressive therapies in the treatment of MMP. The primary outcome was achievement and time to disease control. METHODS: Patients with a diagnosis of MMP from August 2001 to June 2015 who had greater than 6 months of follow-up after the initiation of therapy were reviewed. RESULTS: In all, 24 patients were treated with rituximab and 25 were treated with conventional immunosuppression. Of patients, 100% in the rituximab group achieved disease control compared with 40% in the conventional group (P < .01), with a mean time to disease control of 10.17 months and 37.7 months (P = .02). Adverse events were seen in 33% of patients after rituximab, compared with 48% of patients in the conventional group (P = .2). LIMITATIONS: Rituximab dosing was not uniform and the 2 groups were not matched in terms of disease severity, nor were they randomized. CONCLUSIONS: Our study indicates that the addition of rituximab to conventional therapy in patients with MMP results in more rapid and sustained disease control with potentially fewer adverse events.

Discordance of histopathologic parameters in cutaneous melanoma: Clinical implications.

BACKGROUND: Histopathologic analysis remains the gold standard for the diagnosis of melanoma, however previous studies have shown a substantial rate of interobserver variability in the evaluation of melanocytic lesions. OBJECTIVE: We sought to evaluate discordance in the histopathological diagnosis and microstaging parameters of melanoma and subsequent impact on clinical management. METHODS: This was a retrospective review of 588 cases of cutaneous melanoma and melanoma in situ from January 2009 to December 2014 that were referred to Emory University Hospital, Atlanta, GA, for treatment. Per institutional policy, all outside melanoma biopsy specimens were reviewed internally. Outside and institutional reports were compared. RESULTS: Disagreement between outside and internal reports resulted in a change in American Joint Committee on Cancer pathologic stage in 114/588 (19%) cases, resulting in a change in management based on National Comprehensive Cancer Network guidelines in 105/588 (18%) cases. LIMITATIONS: Given the retrospective nature of data collection and the bias of a tertiary care referral center, cases in this study may not be representative of all melanoma diagnoses. CONCLUSION: These findings confirm consistent subjectivity in the histopathologic interpretation of melanoma. This study emphasizes that a review of the primary biopsy specimen may lead to significant changes in tumor classification, resulting in meaningful changes in clinical management.

Azathioprine treatment of intractable pruritus: A retrospective review.

BACKGROUND: Chronic, severe, treatment-resistant and life-altering pruritus is challenging for both clinician and patient. Pruritus in this population of patients may be immune mediated and respond to immunosuppression, but this approach to treatment has not been investigated in depth. OBJECTIVE: We sought to determine the efficacy and tolerability of azathioprine in the treatment of chronic pruritus responsive to systemic corticosteroids. METHODS: This was a retrospective review of the outcomes of treatment in 96 patients with systemic steroid-responsive pruritus treated with azathioprine. RESULTS: Mean duration of symptoms before treatment was 52.9 months (range 2-360 months, SD 64.8); pretreatment visual analog scale itch score was 9.25/10 (range 3-10, SD 1.37); posttreatment itch was 1.625/10 (range 0-8, SD 1.67) (P < .0001). Suspected drug-related adverse effects developed in 62 (65%) patients and 32 (33%) patients had to permanently discontinue treatment. LIMITATIONS: Because of the uncontrolled retrospective design there were variations in azathioprine dosing. CONCLUSION: Among patients with an extensive history of intractable and life-altering pruritus, therapy with azathioprine may provide substantial relief of symptoms.

Cutaneous melanoma: preoperative tumor diameter in a general dermatology outpatient setting.

BACKGROUND: The ABCD mnemonic for cutaneous melanoma indicates that tumor diameter (D) is typically greater than 6 mm. OBJECTIVE: To determine the distribution of preoperative tumor diameter in a midwestern United States general dermatology practice-based case series. METHODS: Patient records were reviewed for preoperative maximal tumor diameter for primary cutaneous melanomas diagnosed between January 1, 2006, and February 1, 2012. RESULTS: Of 116 tumors for which preoperative measures were available, 38 (32.8%) had a diameter of 6 mm or less. Of these 38 small-diameter (≤6 mm) cases, tumor invasion occurred in 26 (68.4%), compared with 36 of the 78 (46.2%) larger-diameter (>6 mm) cases. Small-diameter tumors were significantly more common in patients younger than 60 and almost twice as common in women than men. CONCLUSIONS: Almost one-third of evaluable tumors in this general dermatology practice-based setting had a preoperative diameter of 6 mm or less, and two-thirds of these small-diameter cases were invasive. The diameter criterion of greater than 6 mm in the ABCD mnemonic is precariously insensitive for a public message.

Bullous systemic lupus erythematosus in a patient with human immunodeficiency virus infection: a paradox of autoimmunity and immunodeficiency.

Bullous lupus erythematosus is a rare variant of systemic lupus erythematosus (SLE) and is characterized by autoantibodies to type VII collagen. Co-existence of SLE and human immunodeficiency virus (HIV) infection is extremely rare; the development of bullous lupus in the setting of HIV has been, to our knowledge, reported in the literature only once. We describe a 26-year-old man with an 8-year history of HIV infection who developed bullous SLE. The patient presented with widespread, tense bullae as well as oral ulcerations. Clinical, laboratory, histological, and cutaneous immunofluorescence findings confirmed the diagnosis of bullous SLE. Given the immunological consequence of HIV infection, the co-occurrence of these two diseases would, theoretically, be unusual. Theories pertaining to the interplay of immunologic mechanisms of the seemingly paradoxical occurrence of autoimmunity in the setting of HIV infection are discussed.

Gentian violet: a 19th century drug re-emerges in the 21st century.

Gentian violet (GV) has a long and varied history as a medicinal agent. Historically used as an antibacterial and antifungal, recent reports have shown its utility as an antitypranosomal, antiviral and anti-angiogenic agent. The objective of this article is to summarize evidence regarding the efficacy and safety of GV use in dermatology. Recent discoveries have found novel targets of GV, namely NADPH oxidase in mammalian cells and thioredoxin reductase 2 in bacterial, fungal and parasitic cells. These discoveries have expanded the use of GV in the 21st century. Given that GV is well tolerated, effective and inexpensive, its use in dermatology is predicted to increase.

Blowing Bubbles: Dermoscopy of Bubble Hair.

Exposing wet hair to high temperatures can create gas bubbles within the hair shaft, leading to brittle, dry hairs in a disorder known as bubble hair abnormality. We present a case of a 61-year-old woman who presented for hair breakage over her crown. She regularly dried her damp hair with a blow dryer. Dermoscopy revealed multiple bubbles within the hair shaft, and diagnosis of bubble hair abnormality was confirmed by light microscopy. Our unusual case highlights the ease of acquisition of this abnormality by means of a common hair dryer, and the utility of dermoscopy to make a fast and accurate diagnosis within the office.

Catatonia and psychosis in a case suggesting Fahr's disease.

Catatonia is a manifestation of several psychiatric disorders, but may also be secondary to a systemic medical condition. Fahr's disease is characterized by radiographic calcifications of the basal ganglia. While diverse neuropsychiatric symptoms have been reported in Fahr's disease, few reports of catatonia in this condition exist. We present a case of psychosis and catatonia in a patient with Fahr's disease.

Compliance and efficacy of titratable thermoplastic versus custom mandibular advancement devices.

OBJECTIVE: To share our experiences treating patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) with titratable thermoplastic (TPD) and custom-made mandibular advancement devices (MAD) and to compare these devices in terms of objective improvement and cure and treatment success (improvement/cure plus adherence at 6 months). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary care center. SUBJECTS AND METHODS: Patients with OSAHS who failed or refused both continuous positive airway pressure (CPAP) and surgery had a titratable oral appliance fitted. Patients were offered an office-fitted TPD or a custom-made dentist-fitted device. Assessment included pretreatment and appliance-titration polysomnography (PSG). Improvement was defined as ≥ 50% apnea-hypopnea index (AHI) reduction plus posttreatment AHI <20, and cure was defined as AHI <5. Patients were contacted at 1 and 6 months regarding treatment adherence. RESULTS: A total of 180 patients (123 TPD, 57 custom) with complete PSG data were reviewed. Improvement/cure were significantly better with the custom device overall (91.2%/71.9% vs 77.2%/52.0%, P = .024/.012). Adherence data at 1 and 6 months were obtained from 128/180 and 119/180 patients, respectively. Using an intention-to-treat analysis, those lost to follow-up were considered nonadherent. Adherence at 1/6 months was 64.9%/50.9% for custom versus 53.7%/32.5% for TPD (P = .156/.018), yielding treatment success rates (with initial improvement/cure) of 49.1%/40.4% for custom versus 27.6%/17.1% for TPD (P = .005/<.001) at 6 months. CONCLUSION: Custom-fit devices achieve higher rates of objective improvement and cure of OSAHS than TPD at the time of titration-PSG. TPDs have a high acceptance rate, low cost, and reasonable initial improvement and cure rates of 77.2% and 52.0%, respectively, but significantly poorer 6-month compliance.

The value of routine pH monitoring in the diagnosis and treatment of laryngopharyngeal reflux.

OBJECTIVE: To assess the need for pH testing in diagnosing laryngopharyngeal reflux (LPR). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary care center. SUBJECTS AND METHODS: On the basis of symptoms and/or abnormal endoscopic findings, more than 500 patients underwent 24-hour pharyngeal pH testing at a single center (using the Dx-pH probe) between January 2009 and June 2011. A total of 163 patients not on proton-pump inhibitors at the time of study and with complete data available for analysis (pH results, body mass index, smoking status, pretest reflux symptom index) were divided into 2 groups by positive (n = 70) and negative (n = 93) Ryan Score. The Reflux Symptom Index (RSI) was compared between groups and assessed overall against Ryan Score parameters at different pH thresholds. The diagnostic utility of an RSI ≥ 13 for prediction of Ryan Score was assessed. RESULTS: No significant difference in RSI was seen between Ryan-positive (17.50 ± 11.47) and Ryan-negative (14.95 ± 11.43) patients (P = .161). Overall, RSI correlated poorly with percentage time spent below pH thresholds 6.5, 6.0, 5.5, and 5.0 and upright and supine Ryan parameters at these thresholds (as determined by linear regression analysis). The sensitivity, specificity, positive predictive value, and negative predictive value of RSI ≥ 13 for Ryan positivity were 55.7%, 47.3%, 44.3%, and 58.7%, respectively. CONCLUSION: Our findings show that in our population of otolaryngology patients, the diagnosis of LPR cannot be reliably made on the basis of symptoms alone. Diagnosis, and in particular treatment decisions, should ideally be made on the basis of a combination of symptoms, signs, and confirmatory testing.

Transoral robotic glossectomy for the treatment of obstructive sleep apnea-hypopnea syndrome.

OBJECTIVE: In previous reports of transoral robotic surgery (TORS) for the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS), patients underwent routine tracheotomy. We aim to assess the feasibility of performing robotically assisted partial glossectomy without tracheotomy and to assess efficacy by comparing OSAHS outcomes with those of established techniques. STUDY DESIGN: Historical cohort study with planned data collection. SETTING: Tertiary care center. SUBJECTS AND METHODS: Forty consecutive patients underwent TORS for OSAHS between October 2010 and June 2011 and were followed up with regard to complications, morbidity, and subjective and objective outcomes. Data from 27 of these patients who underwent concomitant z-palatoplasty with 6-month follow-up were compared with those of 2 matched cohorts of patients, who underwent either radiofrequency (radiofrequency base-of-tongue reduction [RFBOT]) or coblation (submucosal minimally invasive lingual excision [SMILE]) reduction of the tongue base and z-palatoplasty. RESULTS: No major bleeding or airway complications were observed. Postoperative pain and length of admission were similar between groups. All groups saw Epworth score and snore score improvement. Patients undergoing robot-assisted surgery took longer than their SMILE and RFBOT counterparts to tolerate normal diet and longer than RFBOT patients to resume normal activity. Apnea hypopnea index (AHI) reduction averaged 60.5% ± 24.9% for TORS versus 37.0% ± 51.6% (P = .042) and 32.0% ± 43.3% (P = .012) for SMILE and RFBOT, respectively. Only the robotic group achieved statistically significant improvement in minimum oxygen saturation. Surgical cure rate for TORS (66.7%) was significant compared with RFBOT (20.8%, P = .001) but not compared with SMILE (45.5%, P = .135). CONCLUSION: Robotically assisted partial glossectomy feasibly can be performed without the need for tracheotomy. This technique resulted in greater AHI reduction but increased morbidity compared with the other techniques studied.

Dead Sea salt irrigations vs saline irrigations with nasal steroids for symptomatic treatment of chronic rhinosinusitis: a randomized, prospective double-blind study.

BACKGROUND: Intranasal steroids are 1 of the most frequently prescribed medications for the treatment of chronic rhinosinusitis (CRS), and saline irrigations are commonly used as an adjunct to medical therapy. We aimed to compare the efficacy of Dead Sea salt (DSS) irrigations and DSS nasal spray vs saline irrigations and topical nasal steroid spray in the treatment of symptoms of CRS. METHODS: A total of 145 symptomatic adult patients without acute infection were initially enrolled and 114 completed the study. Patients completed a Sino-Nasal Outcomes Test 20 (SNOT-20) survey (primary outcome metric) and underwent endonasal examination, acoustic rhinometry, and smell testing (secondary outcome metrics). Patients were randomized to 2 groups. The experimental group (n = 59) self-administered hypertonic DSS spray and DSS irrigation; the control group (n = 55) self-administered fluticasone spray and hypertonic saline irrigation and spray. Patients and staff were blinded to group assignment. Outcomes were reassessed at 4 weeks. RESULTS: The 2 groups were homogeneous with respect to pretreatment primary and secondary outcome metrics. Dropout rates were 30% in the DSS group and 36.6% in the control group. Both groups showed significant improvement in mean SNOT-20 scores following treatment; however, the degree of improvement was not significantly different between groups (p = 0.082). There were no significant changes in secondary outcome metrics between the 2 groups. CONCLUSION: For patients with CRS, treatment with DSS irrigations and sprays appears as effective for symptom reduction as a combination of hypertonic saline irrigations and sprays and a topical steroid spray.

Modified adenotonsillectomy to improve cure rates for pediatric obstructive sleep apnea: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of adenotonsillectomy (T&A) with and without pharyngoplasty (tonsillar pillar closure) in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome (OSAHS). STUDY DESIGN: Randomized single-blind controlled study. SETTING: Tertiary care center. SUBJECTS AND METHODS: Sixty pediatric patients with a clinical diagnosis of OSAHS presenting between January 2009 and December 2010 were enrolled and randomized to undergo either standard T&A (n = 30) or T&A with pharyngoplasty (n = 30). Surgical cure was defined as apnea-hypopnea index (AHI) <5 plus OSA-18 health-related quality-of-life (HRQL) score <60. Other outcomes included postsurgical AHI and minimum oxygen saturation (SpO(2)) improvement, changes in OSA-18 scores at 1 month, and postsurgical days to resume normal diet and activity. RESULTS: Three patients from each group did not undergo surgery. Of the 54 patients treated, 8 from the pharyngoplasty group and 2 from the standard group were lost to follow-up. Intention-to-treat analysis revealed no difference in cure rate between groups (standard 60%, pharyngoplasty 56.6%, P = .793). Limiting analysis to those patients with complete data, a higher, but not significantly increased, cure rate with pharyngoplasty was noted (72% vs 89.5%, P = .155). Greater OSA-18 improvement (P = .036) and greater (although nonsignificant) AHI improvement and earlier return to normal function were noted with pharyngoplasty. CONCLUSION: The addition of pharyngoplasty to traditional adenotonsillectomy did not significantly improve OSAHS cure rates as measured by sleep testing and HRQL, although a nonsignificant increase in cure rate was observed in those who completed the study protocol. An unexpectedly high rate of patient dropout rendered the study statistically underpowered and therefore inconclusive.