Eosinophils isolated from the blood of aspirin-induced asthma subjects (as well as severe asthmatic patients) greatly overproduce 15-hydroxyicosatetraenoic acid and eoxin C4 when challenged with arachidonic acid or calcium ionophore A23187, compared to the eosinophils taken from normal or mildly asthmatic subjects; aspirin treatment of eosinophils from aspirin intolerant subjects causes the cells to mount a further increase in eoxin production. These results suggest that 15-lipoxygenase and certain of its metabolites, perhaps eoxin C4, is contributing to aspirin-induced asthma in a fashion similar to 5-lipoxygenase and its leukotriene metabolites. Treatment
Medication
Avoidance of NSAID medications will not stop the progression of the disease. The preferred treatment for many patients is desensitization to aspirin, undertaken at a clinic or hospital specializing in such treatment. Patients who are desensitized then take a maintenance dose of aspirin daily to maintain their desensitization. The recommended maintenance dose for symptom control is 650 mg to 1300 mg aspirin daily. While on daily aspirin, most patients have reduced need for supporting medications, fewer asthma and sinusitis symptoms than previously, and an improved sense of smell. Desensitization to aspirin reduces the chance of nasal polyp recurrence and may slow the regrowth of nasal polyps. Once desensitized to aspirin, most patients can safely take other NSAID medications again.Even patients desensitized to aspirin may continue to need other medications including nasal steroids, inhaled steroids, and leukotriene antagonists. Leukotriene antagonists and inhibitors (montelukast, zafirlukast, and zileuton) often are helpful in treating the symptoms of AERD.
This gene codes for cathepsin K, a lysosomal cysteine protease that is highly expressed in osteoclasts and plays a significant role in bone remodelling by degenerating the bone matrix proteins such as type I collagen, osteopontin, and osteonectin. Defective function of cathepsin K therefore results in failure of normal degradation of the accumulated collagen fibres in the resorptive microenvironment by osteoclasts despite normal generation of ruffled membranes and mobilization of bone minerals. If both parents of a diagnosed individual are heterozygous for a CTSK pathogenic variant, siblings of the individual have a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Diagnosis
Pycnodysostosis is one of those disorders which has a typical facial gestalt and can be clinically identified in the majority of cases. Skeletal surveys can also aid in clinical diagnosis and characteristic features include high bone density, acro-osteolysis and obtuse mandibular angle. Molecular testing will be the final resort to confirm the diagnosis. Due to the limited number of exons of the CTSK gene that causes pycnodysostosis, a cheaper genetic testing called Sanger sequencing can be employed to confirm the diagnosis. Treatment and management
The treatment of pycnodysostosis is currently based on symptomatic management and no active trials are in place for a curative approach. The comorbidities like short stature, fracture and maxillofacial issues can be easily managed when identified earlier, which can improve the quality of life of these individuals.