Haploinsufficiency of A20 (HA20): updates on the genetics, phenotype, pathogenesis and treatment.

BACKGROUND: A20, a protein encoded by the tumor necrosis factor alpha-induced protein 3 gene (TNFAIP3), plays a vital role in the negative regulation of inflammation and immunity. Loss-of-function mutation in TNFAIP3 leads to a new described autoinflammatory disease-haploinsufficiency of A20 (HA20). Since HA20 was first described in 2016, a number of new cases have been described in this literature, however, the disease and its pathogenesis are poorly understood. This review seeks to improve clinical recognition of this disorder, and promote both earlier diagnosis and initiation of targeted therapies to improve patients' outcomes. METHODS: We reviewed 26 papers about A20 and HA20, and we summarized genetic variants and clinical manifestations of a total of 61 reported patients from 26 families identified to have a genetic diagnosis of germline pathogenic variants in TNFAIP3/A20. Additionally, we discussed the pathogenesis and treatment of HA20. RESULTS: A total of 24 pathogenic variants of A20 had been reported. There was significant clinical heterogeneity, even among those with the same variants in TNFAIP3. Prior to receiving a molecular diagnosis of HA20, patients had been diagnosed with Behcet's disease, rheumatoid arthritis, rheumatic fever, juvenile idiopathic arthritis, systemic lupus erythematosus, and even adult-onset Stills' disease. The patients with HA20 that presented with inflammatory signatures in NF-κB signaling were mostly responsive to treatment. CONCLUSIONS: HA20 is a monogenic autoinflammatory disease with highly variable clinical manifestations. This extensive heterogeneity makes it difficult to set a clinical diagnostic criteria, and genetic sequencing is necessary for a definitive diagnosis of HA20.

[Repair of deep wound on the head due to high-voltage electrical burn].

OBJECTIVE: To explore the methods for repairing deep wound on the head due to high-voltage electrical burn (HEB). METHODS: Twenty-six patients with deep wounds on the head due to HEB were hospitalized from June 2002 to May 2012. They were all injured by high-voltage (voltage ranged from 380 V to 300 kV) electric current, involving head and several other parts over the body. The total burn area ranged from 1% to 75% TBSA, and the depth ranged from deep partial-thickness to full-thickness (including muscle or even bone). Scalp defect area ranged from 3 cm×2 cm to 20 cm×18 cm, and the maximum size of skull exposure was 12 cm×9 cm and the maximum size of skull defect was 7 cm×6 cm. The wounds of 26 patients were repaired with 7 local advance flaps, 4 bilateral rotation flaps, 18 local rotation flaps combined with thin split-thickness skin grafts in donor site, and 3 free anterolateral thigh flaps with vascular anastomosis. In four of the 26 patients, expander was used in the early stage after burn and 5 after wound healing (with thin split-thickness grafts). RESULTS: All flaps and skin grafts survived, except for one flap which was complicated by wound infection, and it was healed after dressing and secondary suturing. The implanted expander expanded smoothly. Patients were followed up for 15 days to three years after surgery. Satisfactory results were obtained, and wounds of 15 patients were repaired completely. CONCLUSIONS: Deep wound on the head due to HEB should be repaired with suitable flap combined with skin graft in donor site, and implantation of expander according to the injury area and condition of patient.

[Experience in the treatment of severe pressure sore].

OBJECTIVE: To summarize the experience in the treatment of severe pressure sore. METHODS: From Aug. 2007 to Jun. 2011, 21 cases of severe pressure sore with 43 III-IV degree lesions were treated with combination treatment, including vacuum sealing drainage technique, local fascia flaps, upper or lower gluteus maximus island myocutaneous flaps, lower gluteus maximus myocutaneous flap, neurocutaneous femoris posterior flaps, tensor fascia lata island myocutaneous flaps, free latissimus dorsi myocutaneous flaps, and skin graft, combined with stryker frame and nursing tracking guidance. 13 of 21 cases had multiple pressure sore. Among them, 5 III degree pressure sores were covered by skin grafting and 3 non-caudal III degree pressure sores (< 2 cm in width) were directly closed after debridement. 8 of 21 cases had single IV degree pressure sore. RESULTS: All the 43 wounds healed completely. 5 wounds in 3 cases had effusion under flap which healed after re-drainage. The wounds were not healed in 3 cases with flap transposition which were also healed after re-debridement. All the flaps survived completely. 16 cases were followed up for 2-26 months. Recurrence happened in 4 cases after discharge because of not following the required nursing care. CONCLUSIONS: Comprehensive application of vacuum sealing drainage technique, multiple myocutaneous flaps and skin grafting, combined with stryker frame and nursing tracking guidance after discharge can be used for the treatment of severe pressure sore with satisfactory results.

[Reverse small saphenous vein-sural neurovascular island flap for t he reconstruction ofsoft tissue defect on foot and ankle in children].

OBJECTIVE: To investigate the clinical application of reversed small saphenous vein-sural neurovascular island flap for reconstruction of soft tissue defect on foot and ankle in children. METHODS: From July 2006 to June 2008, 8 children with soft tissue defects on foot, heel or ankle were treated with reversed small saphenous vein-sural neurovascular island flaps. The size of flaps ranged from 6 cm x 5 cm to 9 cm x 7 cm. The upper margin of the flaps reached the upper third of cruris, with 1 case reaching the transverse line of popliteal fossa. RESULTS: All the flaps survived. The patients were followed up for 1 - 17 months with good aesthetic and functional results. The growth of the two legs had no difference. The sensation of the flaps improved with no heel ulcer and no dysfunction at the donor site. The upper boundary of flaps can reach the upper third of the cruris even the reansverse line of popliteal fossa. The rotation point of the flaps located at 4 - 6 cm above the lateral ankle in children. CONCLUSIONS: The reversed small saphenous vein-sural neurovascular island flap in children has a reliable survival area. The operation is easily performed without any obvious influence on the growth of the operated cruris. It is a good reconstructive method for soft tissue defect in foot and ankle.

[Repair of high-voltage electric burn in jaw and neck region with insular pectoralis major myocutaneous flap].

OBJECTIVE: To evaluate the effect of insular pectoralis major myocutaneous flap on repair of jaw and neck tissue defect as a result of high-voltage electric burn. METHODS: Eighteen patients with large area tissue defect in jaw and neck caused by high-voltage electric burn hospitalized from August 2001 to December 2007 were repaired with insular pectoralis major myocutaneous flap. The flaps (from 12 cm x 10 cm to 16 cm x 13 cm) was transplanted in 8 patients after early wound debridement, and in 10 patients on infected wounds. RESULTS: All flaps survived wells except in 4 patients necrotic area (length 2-5 cm, width 1-2 cm) appeared in the distal wound edge, localized dehiscence of wound edge in 2 cases, which were healed after dressing change or secondary suturing. Patients were followed up from 6 months to 3 years, and the appearance and function were satisfactory. CONCLUSIONS: Pectoralis major muscle island myocutaneous flap has the advantage of large tissue mass, with thin and flat muscle belly, and rich blood supply, which is suitable for repair of large deep tissue defect in jaw and neck.

[Clinical observation of the efficacy of MEBO in the treatment of burn patients with burn area over 50% TBSA].

OBJECTIVE: To observe the effectiveness of MEBO in the treatment of burn patients with burn area over 50% TBSA. METHODS: Two hundred and ninety-eight patients hospitalized in our hospital from May of 1991 to December of 2003 with burn area over 50% TBSA, who had MEBO treatment before hospitalization, were enrolled in the study as the experiment (E) group. Another group of 300 burn patients with burn area over 50% TBSA that treated with SD-Ag cream were enrolled in the study as the control (C) group. Bacterial culture results, major changes in injury and mortality were compared between the two groups. RESULTS: There were 1 506 bacteria strains isolated from wounds in E group, and 9 main changes in injury (1679 cases) occurred with 20.8% mortality in this group. There were 353 bacteria strains isolated, with occurrence of 9 changes in injury (518 cases) and 4.7% mortality in the SD-Ag group. CONCLUSION: MEBO is much less effective for the treatment of the burn patients with large burn area compared with SD-Ag cream treatment.

[Effects of comprehensive interventions in community on smoking, chronic bronchitis, and asthma in rural areas of Beijing].

OBJECTIVE: To study the effects of comprehensive interventions in community on smoking, chronic bronchitis, and asthma in rural areas of Beijing. METHODS: Twenty-three villages in rural areas of Beijing were randomly divided into interventional (13 villages) and control villages (10 villages) in 1992. Comprehensive interventions including education of former-smokers and improvement of living environment were carried out in the interventional villages, and none was done in the control villages. In April 2000, surveys on smoking, chronic bronchitis, and asthma were carried out among 34,436 participants aged 15 or more in the interventional and control villages. During the same period, knowledge on prevention from chronic obstructive pulmonary diseases (COPD), living environments, and smoking were assessed among 1658 high-risk individuals of COPD at baseline and following-up period. RESULTS: The scores of knowledge and improvement on living environments in the interventional villages were significantly higher than those in control villages (P < 0.001). The decrease rate of smoking and current smoking rate in the interventional villages were significantly higher than in the control villages (0.4% vs -0.8%, P < 0.001; 2.4% vs 1.3%, P < 0.001) in men, while not different in women (P > 0.05). Among never smokers at baseline, the accumulated incidence of smoking among people aged 15 to 24 from 1993 to 2000 was significantly lower in the interventional villages than in the control villages in men (18.9% vs 23.7%, P = 0.005) and in women (0% vs 0.7%, P = 0.005). Daily cigarettes smoked by smokers in the interventional villages were less than in control villages in both men (14.8 +/- 7.0 vs 17.2 +/- 8.2 cigs daily, P < 0.001) and women (12.8 +/- 6.9 vs 13.4 +/- 7.2 cigs daily, P = 0.088). The increase of prevalence of chronic bronchitis in the interventional villages was less than in the control villages (men: 0.9% vs 1.3%, P = 0.012; women: 0.1% vs 0.3%, P = 0.003). After the age factor is adjusted, odds ratio (OR) for accumulated incidence of chronic bronchitis from 1993 to 2000 in the interventional villages were 0.80 (95%CI: 0.60-1.07) for men, 0.76 (95%CI: 0.45-1.28) in women. The OR for asthma was not significant in both men and women. CONCLUSIONS: Comprehensive interventions in community may improve knowledge of COPD prevention and living environments, decrease the smoking rate, cigarettes smoked per day, and incidence of chronic bronchitis, but have no significant effects on asthma.