Cause
Netherton syndrome is an autosomal recessive disorder associated with mutations in the SPINK5 gene, which encodes the serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI). These mutations result in a dysfunctional protein that has a reduced capacity to inhibit serine proteases expressed in the skin. Potential endogenous targets of LEKTI include KLK5, KLK7 and KLK14. These enzymes are involved in various aspects of epidermal remodelling, including desquamation, PAR-2 activation and degradation of lipid hydrolases, suggesting a potential mechanism for the development of atopic manifestations characteristic of Netherton syndrome.Disease severity is determined by the level of LEKTI expression and, consequently, serine protease activity. Complete SPINK5 gene deletions have been linked to severe cases, while mutations which induce alternate splicing or create premature stop codons may lead to varying levels of severity. Furthermore, LEKTI-knockout mice exhibit a phenotype similar to Netherton syndrome in humans. Diagnosis
Treatment
There is no known cure at the moment but there are several things that can be done to relieve the symptoms. Moisturising products are very helpful to minimize the scaling/cracking, and anti-infective treatments are useful when appropriate because the skin is very susceptible to infection. Extra protein in the diet during childhood is also beneficial, to replace that which is lost through the previously mentioned "leaky" skin.Steroid and retinoid products have been proven ineffective against Netherton syndrome, and may in fact make things worse for the affected individual.Intravenous immunoglobulin has become established as the treatment of choice in Nethertons syndrome.
Dipyridamole (trademarked as Persantine and others) is a nucleoside transport inhibitor and a PDE3 inhibitor medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a short time. Medical uses
Dipyridamole is used to dilate blood vessels in people with peripheral arterial disease and coronary artery disease
Dipyridamole has been shown to lower pulmonary hypertension without significant drop of systemic blood pressure
It inhibits formation of pro-inflammatory cytokines (MCP-1, MMP-9) in vitro and results in reduction of hsCRP in patients. It inhibits proliferation of smooth muscle cells in vivo and modestly increases unassisted patency of synthetic arteriovenous hemodialysis grafts. It increases the release of tissue plasminogen activator from brain microvascular endothelial cells. It results in an increase of 13-hydroxyoctadecadienoic acid and decrease of 12-hydroxyeicosatetraenoic acid in the subendothelial matrix and reduced thrombogenicity of the subendothelial matrix. Pretreatment it reduced reperfusion injury in volunteers. It has been shown to increase myocardial perfusion and left ventricular function in patients with ischemic cardiomyopathy. It results in a reduction of the number of thrombin and PECAM-1 receptors on platelets in stroke patients. Cyclic adenosine monophosphate impairs platelet aggregation and also causes arteriolar smooth muscle relaxation. Chronic therapy did not show significant drop of systemic blood pressure. It inhibits the replication of mengovirus RNA. It can be used for myocardial stress testing as an alternative to exercise-induced stress methods such as treadmills.