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Clinical Immunology (Orlando, Fla.) Jun 2024OTULIN encodes an eponymous linear deubiquitinase (DUB) essential for controlling inflammation as a negative regulator of the canonical NF-κB signaling pathway via the...
OTULIN encodes an eponymous linear deubiquitinase (DUB) essential for controlling inflammation as a negative regulator of the canonical NF-κB signaling pathway via the regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections. At the same time, a recent novel ORAS-like inflammatory syndrome was described in association with a heterozygous missense mutation that appears to exert dominant negative (DN) effects. In this manuscript, we report the identification of a novel homozygous missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan infant with an ORAS phenotype and provide experimental evidence for its pathogenicity. We go on to systematically review the literature for OTULIN-associated conditions by using the GenIA database (www.geniadb.net) to collect, extract and harmonize all clinical, laboratory and functional data for published patients and variants. Our comprehensive synthesis of genotypic, phenotypic, and mechanistic data enables a more in-depth view of the diverse mechanisms and pathways by which the OTULIN pathogenic variants may lead to human immune disease. This review may help variant classification activities and inform future variant evaluation, as well as the development of diagnostic and management guidelines. It also identifies current knowledge gaps and raises additional questions warranting future investigation.
PubMed: 38914362
DOI: 10.1016/j.clim.2024.110292 -
Pediatric Blood & Cancer Mar 2024
Topics: Humans; Pancreas; Pancreatitis; Panniculitis; Arthritis; Sarcoma; Cytoskeletal Proteins; Armadillo Domain Proteins
PubMed: 38110803
DOI: 10.1002/pbc.30819 -
Medicina Clinica Mar 2024
Topics: Humans; Ascites; Pancreatitis; Pancreatic Diseases; Panniculitis; Arthritis
PubMed: 38044189
DOI: 10.1016/j.medcli.2023.09.022 -
European Journal of Internal Medicine Nov 2023
Topics: Male; Humans; Subcutaneous Fat; Osteonecrosis; Necrosis; Arthritis
PubMed: 37537031
DOI: 10.1016/j.ejim.2023.07.044 -
Journal of Plastic, Reconstructive &... Apr 2024Subcutaneous fat necrosis of the newborn (SCFN) is a rare form of panniculitis manifesting as erythematous plaques or nodules at sites of brown fat in neonates. Surgical... (Review)
Review
BACKGROUND
Subcutaneous fat necrosis of the newborn (SCFN) is a rare form of panniculitis manifesting as erythematous plaques or nodules at sites of brown fat in neonates. Surgical management may be indicated in severe cases; however, there is a paucity of literature compiling presentations and outcomes of these surgical patients.
METHODS
The authors performed a systematic review, in consultation with a licensed librarian, on MEDLINE and Embase for studies including patients with SCFN who were surgically managed.
RESULTS
The search strategy generated 705 results, among which 213 (30.2%) were excluded for lack of discussion on surgical management. Twenty-two studies discussed surgical management of SCFN in 26 patients, but in 6 of these studies the patients were not surgically managed. Ultimately, 16 articles with 16 patients who were surgically managed were included in the study. Average age at diagnosis was 11.8 ± 9.8 days; average age at surgery was 39.5 ± 70.4 days. The most common etiologies were "unknown" (6, 37.5%), therapeutic hypothermia (4, 25.0%), and birth complications (4, 25.0%). Patients harbored nodules on the back (14, 87.5%), upper extremities (7, 43.8%), lower extremities (7, 43.8%), buttocks (5, 31.3%), and head or neck (3, 18.8%). Linear regression models revealed the presence of back lesions and predicted concomitant medical complications (β = 2.71, p = 0.021).
CONCLUSIONS
Patients undergoing surgical management for SCFN most commonly harbor lesions on the back and extremities that are secondary to therapeutic hypothermia or of unknown origin. Reporting of additional cases is needed to further elucidate surgical management and outcomes.
Topics: Infant, Newborn; Humans; Infant; Subcutaneous Fat; Fat Necrosis; Panniculitis; Hypothermia, Induced; Buttocks
PubMed: 38442509
DOI: 10.1016/j.bjps.2024.02.027 -
Journal of Diabetes Investigation Jun 2024The potential liability to hypercatabolism in lipodystrophy remains to be fully elucidated. Here we report a 28-year-old Japanese woman with acquired generalized...
The potential liability to hypercatabolism in lipodystrophy remains to be fully elucidated. Here we report a 28-year-old Japanese woman with acquired generalized lipodystrophy, who presented with recurrence of panniculitis and anemia. After corticosteroid treatment was started, she showed rapid reductions in body weight and lean mass by 15% at maximum, accompanied by an elevated urea nitrogen/creatinine ratio, which recovered almost fully as the corticosteroid treatment was tapered and discontinued. She had multiple risk factors for hypercatabolism: lack of metabolic reserves, insulin resistance, and hyperglycemia due to lipodystrophy, lowered daily activity due to anemia, persistent inflammation, and wasting associated with panniculitis, and relatively insufficient energy and protein intake during hospitalization. More attention should be paid to the potential liability to hypercatabolism in patients with lipodystrophy, and to skeletal muscle loss as an adverse effect of corticosteroid treatment in patients at high risk, such as those with diabetes or decreased metabolic reserves.
Topics: Humans; Female; Adult; Lipodystrophy; Muscle, Skeletal; Adrenal Cortex Hormones
PubMed: 38372649
DOI: 10.1111/jdi.14158 -
Revista Espanola de Enfermedades... Jun 2024Pancreatitis, panniculitis and polyarthritis syndrome (PPP syndrome) is a clinical syndrome with cutaneous panniculitis and polyarthritis on the basis of pancreatic...
Pancreatitis, panniculitis and polyarthritis syndrome (PPP syndrome) is a clinical syndrome with cutaneous panniculitis and polyarthritis on the basis of pancreatic diseases, which is quite rare. The occurrence of arthrosis and skin lesions is not completely synchronous with pancreatic diseases, so it is often missed or misdiagnosed due to the lack of obvious abdominal signs, with severe sequelae and high mortality. In this article, we report a case of PPP syndrome with severe rare osseous complications caused by chronic pancreatitis.
Topics: Humans; Panniculitis; Arthritis; Fat Necrosis; Syndrome; Male; Pancreatitis; Middle Aged
PubMed: 37350651
DOI: 10.17235/reed.2023.9766/2023 -
Cureus Jan 2024We 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...
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.
PubMed: 38274602
DOI: 10.7759/cureus.52925 -
Clinical, Cosmetic and Investigational... 2023Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis characterized by clinical manifestations such as skin erythema, nodules, fever,...
BACKGROUND
Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis characterized by clinical manifestations such as skin erythema, nodules, fever, pancytopenia, liver failure, plasmacytosis, and hepatosplenomegaly. We report a case of CHP that was initially misdiagnosed as subcutaneous panniculitis-like T-cell lymphoma (SPTCL) but achieved complete remission with a favorable prognosis.
METHODS
A 38-year-old female presented to the dermatology department with a 15-day history of subcutaneous nodules, generalized edema, and continuous fever.
RESULTS
The patient was diagnosed as CHP combined with hemophagocytic syndrome by typical clinical manifestations, low value of SUVmax in positron emission tomography/computed tomography (PET/CT), benign differentiated T cells, negative TCR gene rearrangement, pancytopenia, abnormal coagulation, hypertriglyceridemia, decreased NK cell count, impaired liver function, and the presence of hemophagocytic cells observed in bone biopsy smears.
CONCLUSION
In our case, the patient presented with hemophagocytic syndrome with hemodynamic instability, indicating an intensive treatment is needed. The diagnosis of SPTCL necessitates a meticulous process of differential diagnosis, along with the cautious administration of an aggressive chemotherapy regimen. Extended follow-up is imperative to ascertain the long-term outcomes.
PubMed: 38107669
DOI: 10.2147/CCID.S437208 -
Dermatology Online Journal Dec 2023Pancreatic panniculitis is an uncommon manifestation of pancreatic disease, affecting approximately 2-3% of patients with acute or chronic pancreatitis [1]. Its accurate...
Pancreatic panniculitis is an uncommon manifestation of pancreatic disease, affecting approximately 2-3% of patients with acute or chronic pancreatitis [1]. Its accurate diagnosis is crucial for effective treatment as skin manifestations usually precede systemic symptoms of pancreatitis. The diagnosis of pancreatic panniculitis requires identifying and confirming pancreatic disease in addition to the typical histopathological findings of lobular panniculitis without vasculitis. Herein, we present a patient with pancreatic panniculitis, underlying acute pancreatic failure, and kidney injury.
Topics: Humans; Panniculitis; Pancreatic Diseases; Diagnosis, Differential
PubMed: 38478676
DOI: 10.5070/D329663005