The fact that eTG has been found in precipitates of skin-bound IgA from skin affected by this condition has been used to conclude that dermatitis herpetiformis may be caused by a deposition of both IgA and eTG within the dermis. It is estimated that these deposits may resorb after ten years of following a gluten-free diet. Moreover, it is suggested that this condition is closely linked to genetics. This theory is based on the arguments that individuals with a family history of gluten sensitivity who still consume foods containing gluten are more likely to develop the condition as a result of the formation of antibodies to gluten. These antibodies cross-react with eTG, and IgA/eTG complexes deposit within the papillary dermis to cause the lesions of dermatitis herpetiformis. These IgA deposits may disappear after long-term (up to ten years) avoidance of dietary gluten.Gliadin proteins in gluten are absorbed by the gut and enter the lamina propria where they need to be deamidated by tissue transglutaminase (tTG). tTG modifies gliadin into a more immunogenic peptide. Classical dendritic cells (cDCs) endocytose the immunogenic peptide and if their pattern recognition receptors (PRRs) are stimulated by pathogen-associated molecular patterns (PAMPs) or danger-associated molecular pattern (DAMPs), the danger signal will influence them to secrete IL-8 (CXCL8) in the lamina propria, recruiting neutrophils. Neutrophil recruitment results in a very rapid onset of inflammation.
Diagnosis
Congenital myasthenic syndrome (CMS) is "often difficult to diagnose because of a broad differential diagnosis and lack of specific laboratory findings. Identification of the underlying mutation is critical, as certain mutations lead to treatment-responsive conditions while others do not." Whole exome sequencing (WES) is often used as a diagnostic tool that allows for the "initiation of specific treatment". Management
Treatment depends on the form (category) of the disease. Although symptoms are similar to myasthenia gravis, treatments used in MG are not useful in CMS. MG is treated with immunosuppressants, but CMS is not an autoimmune disorder. Instead, CMS is genetic and responds to other forms of drug treatments. A form of presynaptic CMS is caused by an insufficient release of acetylcholine (ACh) and is treated with cholinesterase inhibitors.Postsynaptic fast-channel CMS, in which ACh receptors do not stay open long enough, is treated with cholinesterase inhibitors and 3,4-diaminopyridine. In the U.S., the more stable phosphate salt formulation of 3,4-diaminopyridine (amifampyridine phosphate) is under development as an orphan drug for CMS and is available to eligible patients at no cost under an expanded access program. Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which blocks the ACh receptor.Ephedrine, a β(2)-adrenergic receptor agonist with alpha activity,  has been tested on patients in clinical trials and appears to be an effective treatment for DOK7 CMS. Most patients tolerate this type of treatment and improvements in strength can be substantial.