A Case Report on Scleroderma: A Diagnostic Dilema

Scleroderma is a rare heterogenous group of autoimmune fibrosing disorder that mainly exists in two forms; localized scleroderma (LS) and systemic sclerosis (SSc). It involves thickening of the skin at fingers region extending from proximal to metacarpophalangeal joints. The diagnostic criteria of scleroderma include past history of patient, symptoms of patient, serology, and skin biopsy. The morbidity and mortality are much worse for SSc with the patients are at risk for life threatening lung, heart and other visceral organ fibrosis and vasculopathy. There is no drug that can cure or stop scleroderma over fibrosis, but certain drugs regulate the symptoms associated with it and boost the patient's quality of life, particularly steroidal creams that help alleviate swelling, joint pain, loosen tight skin; blood pressure drugs that dilate blood vessels; immunosuppressive agents. If the disease is severe amputation is necessary.

The ADAMTS/Fibrillin Connection: Insights into the Biological Functions of ADAMTS10 and ADAMTS17 and Their Respective Sister Proteases

Secreted a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS) proteases play crucial roles in tissue development and homeostasis. The biological and pathological functions of ADAMTS proteases are determined broadly by their respective substrates and their interactions with proteins in the pericellular and extracellular matrix. For some ADAMTS proteases, substrates have been identified and substrate cleavage has been implicated in tissue development and in disease. For other ADAMTS proteases, substrates were discovered in vitro, but the role of these proteases and the consequences of substrate cleavage in vivo remains to be established. Mutations in ADAMTS10 and ADAMTS17 cause Weill–Marchesani syndrome (WMS), a congenital syndromic disorder that affects the musculoskeletal system (short stature, pseudomuscular build, tight skin), the eyes (lens dislocation), and the heart (heart valve abnormalities). WMS can also be caused by mutations in fibrillin-1 (FBN1), which suggests that ADAMTS10 and ADAMTS17 cooperate with fibrillin-1 in a common biological pathway during tissue development and homeostasis. Here, we compare and contrast the biochemical properties of ADAMTS10 and ADAMTS17 and we summarize recent findings indicating potential biological functions in connection with fibrillin microfibrils. We also compare ADAMTS10 and ADAMTS17 with their respective sister proteases, ADAMTS6 and ADAMTS19; both were recently linked to human disorders distinct from WMS. Finally, we propose a model for the interactions and roles of these four ADAMTS proteases in the extracellular matrix.