Two Familial Cases of Epidermolysis Bullosa Simplex Successfully Treated With Tetracycline

Malkinson, Frederick D.; Retief, Carla R.; Pearson, Roger

doi:10.1001/archderm.135.8.997

Cited by 29 publications

(6 citation statements)

References 4 publications

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“…Biologics therapy targeting TNF-α or IL-12/23 p40 suppress skin lesions and by this mechanism reduces the risk of vascular complications [22]. In EB, The skin pathological phenotype of EB is caused by inflammation and by minor trauma as previous demonstrated [23], [24]. The IL-1β signaling is constitutively activated in EB keratinocytes [25], and the serum IL-1α and IL-1β levels are several-fold increased even in the mild type of EB [26].…”

Section: Discussionmentioning

confidence: 89%

Persistent Release of IL-1s from Skin Is Associated with Systemic Cardio-Vascular Disease, Emaciation and Systemic Amyloidosis: The Potential of Anti-IL-1 Therapy for Systemic Inflammatory Diseases

et al. 2014

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The skin is an immune organ that contains innate and acquired immune systems and thus is able to respond to exogenous stimuli producing large amount of proinflammatory cytokines including IL-1 and IL-1 family members. The role of the epidermal IL-1 is not limited to initiation of local inflammatory responses, but also to induction of systemic inflammation. However, association of persistent release of IL-1 family members from severe skin inflammatory diseases such as psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and desmoglein-1 deficiency syndrome with diseases in systemic organs have not been so far assessed. Here, we showed the occurrence of severe systemic cardiovascular diseases and metabolic abnormalities including aberrant vascular wall remodeling with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty tissue loss and systemic amyloid deposition in multiple organs with liver and kidney dysfunction in mouse models with severe dermatitis caused by persistent release of IL-1s from the skin. These morbid conditions were ameliorated by simultaneous administration of anti-IL-1α and IL-1β antibodies. These findings may explain the morbid association of arteriosclerosis, heart involvement, amyloidosis and cachexia in severe systemic skin diseases and systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy for systemic inflammatory diseases.

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Section: Discussionmentioning

confidence: 89%

Persistent Release of IL-1s from Skin Is Associated with Systemic Cardio-Vascular Disease, Emaciation and Systemic Amyloidosis: The Potential of Anti-IL-1 Therapy for Systemic Inflammatory Diseases

et al. 2014

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“…Reduction of blister formation was reported in a small group of EBS patients after administration of tetracycline orally over a period of several weeks [20], [21]. The patients comprised a heterogeneous group that included Dowling-Meara and EBS-localized patients (formerly known as Weber-Cockayne).…”

Section: Discussionmentioning

confidence: 99%

MMP-9 and CXCL8/IL-8 Are Potential Therapeutic Targets in Epidermolysis Bullosa Simplex

et al. 2013

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Epidermolysis bullosa refers to a group of genodermatoses that affects the integrity of epithelial layers, phenotypically resulting in severe skin blistering. Dowling-Meara, the major subtype of epidermolysis bullosa simplex, is inherited in an autosomal dominant manner and can be caused by mutations in either the keratin-5 (K5) or the keratin-14 (K14) gene. Currently, no therapeutic approach is known, and the main objective of this study was to identify novel therapeutic targets. We used microarray analysis, semi-quantitative real-time PCR, western blot and ELISA to identify differentially regulated genes in two K14 mutant cell lines carrying the mutations K14 R125P and K14 R125H, respectively. We found kallikrein-related peptidases and matrix metalloproteinases to be upregulated. We also found elevated expression of chemokines, and we observed deregulation of the Cdc42 pathway as well as aberrant expression of cytokeratins and junction proteins. We further demonstrated, that expression of these genes is dependent on interleukin-1 β signaling. To evaluate these data in vivo we analysed the blister fluids of epidermolysis bullosa simplex patients vs. healthy controls and identified matrix metalloproteinase-9 and the chemokine CXCL8/IL-8 as potential therapeutic targets.

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“…Although a trend of efficacy was noted in one study (10), neither study demonstrated a statistically significant reduction in the number of lesions during treatment with oxytetracycline compared with placebo (10,11). The potential mechanism of action of tetracycline is unknown, but has been postulated to include not only its antibacterial but also its anti‐inflammatory effects (12,13). Topical antibiotics and local wound care are mainstays of treatment for patients with EB, although little evidence‐based medicine for their use is available.…”

Section: Commentmentioning

confidence: 99%

Common Wound Colonizers in Patients with Epidermolysis Bullosa

Brandling‐Bennett

Morel

2010

Pediatric Dermatology

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One of the major morbidities of patients with epidermolysis bullosa is the tendency to develop chronic wounds, which predisposes them to multiple complications including life-threatening infections, failure to thrive, and squamous cell carcinomas. Chronic wounds frequently become colonized with bacteria, and we sought to identify the most common microorganisms isolated on cultures from patients with epidermolysis bullosa. We conducted a retrospective review of positive wound, nasal, and blood cultures, including bacterial, fungal and viral, in 30 patients with epidermolysis bullosa. Staphylococcus sp., Streptococcus sp., diptheroids, Pseudomonas aeruginosa, and Candida sp. were the most commonly isolated microorganisms in wound cultures from our epidermolysis bullosa patients. Two patients had viral cultures that grew herpes simplex virus type-1. Bacterial colonization of chronic wounds can lead to infections and may also impact wound healing. Results from this study provide data on which to base empiric antibiotic choice in patients with epidermolysis bullosa when needed and may be useful in planning strategies for decolonization and improved wound healing in this population.

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Two Familial Cases of Epidermolysis Bullosa Simplex Successfully Treated With Tetracycline

Cited by 29 publications

References 4 publications

Persistent Release of IL-1s from Skin Is Associated with Systemic Cardio-Vascular Disease, Emaciation and Systemic Amyloidosis: The Potential of Anti-IL-1 Therapy for Systemic Inflammatory Diseases

Persistent Release of IL-1s from Skin Is Associated with Systemic Cardio-Vascular Disease, Emaciation and Systemic Amyloidosis: The Potential of Anti-IL-1 Therapy for Systemic Inflammatory Diseases

MMP-9 and CXCL8/IL-8 Are Potential Therapeutic Targets in Epidermolysis Bullosa Simplex

Common Wound Colonizers in Patients with Epidermolysis Bullosa

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