RESUMO
We present a unique case of pancreatic panniculitis (PP) in a 42-year-old male with a history of pancreas-after-kidney (PAK) transplant. The patient developed PP due to acute pancreas allograft rejection. Clinical manifestations included fevers, myalgias, arthralgias, and tender erythematous subcutaneous nodules on the lower extremities. A recent hospital admission was noted for acute pancreas allograft rejection related to low tacrolimus levels. Rheumatological and infectious disease workups were negative. Skin nodule punch biopsy confirmed PP with lobular panniculitis, necrotic adipocytes, basophilic debris, and calcification. Pancreatic biopsy showed evidence of parenchymal acute cellular rejection. Lipase and amylase levels were elevated (1781 U/L and 881 U/L, respectively). Treatment involved pulse solumedrol and thymoglobulin for pancreatic rejection, alongside adjustments to immunosuppressive medications. This case highlights the rarity of PP in a PAK recipient and its association with acute pancreas allograft rejection. Importantly, it is the first reported case of PP occurring solely in the context of pancreas transplant rejection, without concurrent kidney damage or rejection. Prompt diagnosis and management led to the resolution of skin and systemic symptoms. In conclusion, this report presents a clinically relevant and unique case of PP resulting from acute pancreas allograft rejection in a PAK transplant recipient. The findings underscore the importance of early diagnosis and management for positive patient outcomes, serving as a reminder to consider underlying pancreatic pathology when encountering PP in transplant recipients.
RESUMO
The production of melanin increases skin pigmentation and reduces the risk of skin cancer. Melanin production depends on the pH of melanosomes, which are more acidic in lighter-skinned than in darker-skinned people. We showed that inhibition of soluble adenylyl cyclase (sAC) controlled pigmentation by increasing the pH of melanosomes both in cells and in vivo. Distinct from the canonical melanocortin 1 receptor (MC1R)-dependent cAMP pathway that controls pigmentation by altering gene expression, we found that inhibition of sAC increased pigmentation by increasing the activity of tyrosinase, the rate-limiting enzyme in melanin synthesis, which is more active at basic pH. We demonstrated that the effect of sAC activity on pH and melanin production in human melanocytes depended on the skin color of the donor. Last, we identified sAC inhibitors as a new class of drugs that increase melanosome pH and pigmentation in vivo, suggesting that pharmacologic inhibition of this pathway may affect skin cancer risk or pigmentation conditions.