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Therapeutic Advances in Chronic Disease 2021Alpha-1 antitrypsin (AAT) deficiency (AATD) is an autosomal co-dominant condition that predisposes to the development of lung disease, primarily emphysema. Emphysema... (Review)
Review
Alpha-1 antitrypsin (AAT) deficiency (AATD) is an autosomal co-dominant condition that predisposes to the development of lung disease, primarily emphysema. Emphysema results from the breakdown of lung matrix elastin by proteases, including neutrophil elastase, a protease normally inhibited by AAT. AATD also predisposes to liver (cirrhosis) and skin (panniculitis) disease, and to vasculitis. The prevalence of AATD is estimated to be approximately 1 in 3,500 individuals in the United States. However, lack of awareness of AATD among some physicians, misperceptions regarding the absence of effective therapy, and the close overlap in symptoms with asthma and non-AATD chronic obstructive pulmonary disease are thought to contribute to under-recognition of the disease. In patients with AATD, treatment with intravenous AAT augmentation therapy is the only currently available treatment known to slow the progression of emphysema. Moreover, smoking cessation and other lifestyle interventions also help improve outcomes. Early diagnosis and intervention are of key importance due to the irreversible nature of the resultant emphysema. Liver disease is the second leading cause of death among patients with AATD and a minority of patients present with panniculitis or antineutrophil cytoplasmic antibody-associated vasculitis, thought to be directly related to AATD. Though no randomized trial has assessed the effectiveness of augmentation therapy for AATD-associated panniculitis, clinical experience and case series suggest there is a benefit. Other diseases putatively linked to AATD include aneurysmal disease and multiple neurological conditions, although these associations remain speculative in nature.
PubMed: 34408829
DOI: 10.1177/2040622321995691 -
Frontiers in Medicine 2023Behçet disease (BD) and relapsing polychondritis (RP) are chronic multisystem disorders characterized by recurrent flare-ups of tissue inflammation. Major clinical... (Review)
Review
Behçet disease (BD) and relapsing polychondritis (RP) are chronic multisystem disorders characterized by recurrent flare-ups of tissue inflammation. Major clinical manifestations of BD are oral aphthae, genital aphthous ulcers, skin lesions, arthritis, and uveitis. Patients with BD may develop rare but serious neural, intestinal, and vascular complications, with high relapse rates. Meanwhile, RP is characterized by the inflammation of the cartilaginous tissues of the ears, nose, peripheral joints, and tracheobronchial tree. Additionally, it affects the proteoglycan-rich structures in the eyes, inner ear, heart, blood vessels, and kidneys. The mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is a common characteristic of BD and RP. The immunopathology of these two diseases may be closely related. It is established that the genetic predisposition to BD is related to the human leukocyte antigen (HLA)-B51 gene. Skin histopathology demonstrates the overactivation of innate immunity, such as neutrophilic dermatitis/panniculitis, in patients with BD. Monocytes and neutrophils frequently infiltrate cartilaginous tissues of patients with RP. Somatic mutations in UBA1, which encodes a ubiquitylation-related enzyme, cause vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) with severe systemic inflammation and activation of myeloid cells. VEXAS prompts auricular and/or nasal chondritis, with neutrophilic infiltration around the cartilage in 52-60% of patients. Thus, innate immune cells may play an important role in the initiation of inflammatory processes underlying both diseases. This review summarizes the recent advances in our understanding of the innate cell-mediated immunopathology of BD and RP, with a focus on the common and distinct features of these mechanisms.
PubMed: 37435539
DOI: 10.3389/fmed.2023.1055753 -
Balkan Medical Journal May 2023Type 1 interferonopathy is a novel context reflecting a group of inborn disorders sharing common pathway disturbances. This group of diseases is characterized by...
Type 1 interferonopathy is a novel context reflecting a group of inborn disorders sharing common pathway disturbances. This group of diseases is characterized by autoimmunity and autoinflammation caused by an upregulation of type 1 interferons (IFN)s due to certain genetic mutations. Several features are common in most of the diseases in this group, such as vasculitic skin changes, including chilblains, panniculitis, interstitial lung disease, basal ganglion calcifications, neuromotor impairments, epilepsy, stroke, and recurrent fever. Family history and consanguineous marriage are also common. IFN signature is a useful diagnostic tool and is positive in almost all patients with type 1 interferonopathies. Although IFN signature is a sensitive test, its specificity is relatively low. It can also be positive in viral infections and several connective tissue diseases. Therefore, next-generation sequence methods, whole exome sequencing (WES) in particular, are required for the ultimate diagnosis. The optimal treatment regime is still under debate due to a lack of clinical trials. Although high-dose steroids, anti-IL-1 and anti-IL-6 treatments, and reverse transcriptase inhibitors are used, JAK inhibitors are highly promising. Additionally, monoclonal antibodies against IFN-alpha and interferon-α receptor (IFNAR) are currently underway.
Topics: Humans; Mutation
PubMed: 37161741
DOI: 10.4274/balkanmedj.galenos.2023.2023-4-78 -
Haematologica Oct 2023Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis... (Meta-Analysis)
Meta-Analysis
Germline mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis.
Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age <18 years (P=0.04) were associated with HLH, corresponding to the inverse correlation between age and HLH-2004 score (r=-0.40; P=0.02). Homozygous HAVCR2Y82C mutation was more common in the presence of HLH compared with the absence (75.0% vs. 44.4%; P=0.02). Using IPD from the present and the other three eligible cohorts (N=127), male sex, heterozygous and homozygous/compound heterozygous HAVCR2 mutations were associated with HLH by the adjusted odds ratio of 2.93 (95% confidence interval [CI]: 1.22-7.06), 4.77 (95% CI: 1.05-21.63) and 8.48 (95% CI: 2.98-24.10), respectively. Patients with male sex and/or germline HAVCR2 mutations showed an increased risk of developing HLH. Younger patients tended to manifest with HLH, while older patients typically presented with SPTCL with less frequent HLH/HLH-like systemic illnesses.
Topics: Humans; Male; Adolescent; Lymphohistiocytosis, Hemophagocytic; Panniculitis; Germ-Line Mutation; Germ Cells; Hepatitis A Virus Cellular Receptor 2; Multicenter Studies as Topic
PubMed: 37051767
DOI: 10.3324/haematol.2022.282419 -
Annals of Medicine and Surgery (2012) Aug 2022Mesenteric Panniculitis (MP) is predominately a disease of the small bowel of unknown etiology. Characterized by Fibrosis and chronic inflammation of fatty tissue of the... (Review)
Review
Mesenteric Panniculitis (MP) is predominately a disease of the small bowel of unknown etiology. Characterized by Fibrosis and chronic inflammation of fatty tissue of the mesentery in the small bowel. It is commonly diagnosed based on computed tomography (CT scan) with IV contrast and biopsies in equivocal cases. We a retrospective study from 2011 to 2020. We analyzed the medical records of 40 patients with Mesenteric Panniculitis. The most common presentation was vague abdominal symptoms. We successfully managed the patients medically with prednisone, azathioprine, colchicine, Patients on prednisolone showed good responses clinically and radiologically during follow-up. One patient was operated on and didn't respond to medical therapy.
PubMed: 36045792
DOI: 10.1016/j.amsu.2022.104203 -
Cureus May 2024Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome presents a unique challenge in diagnosis and management because of its rarity and heterogeneous initial...
Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome presents a unique challenge in diagnosis and management because of its rarity and heterogeneous initial presentation. This manuscript presents a case series of two patients with PPP syndrome, shedding light on the diagnostic process and care for this uncommon condition. PPP syndrome is characterized by the simultaneous occurrence of pancreatitis or pseudocysts alongside polyarthritis and panniculitis. While its exact pathophysiology remains obscure, pancreatic inflammation is assumed to trigger the hematogenous dissemination of pancreatic enzymes, leading to fat necrosis and subsequent panniculitis, as well as chondronecrosis and/or osteonecrosis causing polyarthritis. Despite its recognition in medical literature since the late 1980s, PPP syndrome remains poorly understood, with only a limited number of cases reported globally. Its rarity and varied initial manifestations often result in misdiagnosis, causing delays in appropriate treatment. The presented case series highlights key clinical features and diagnostic clues of PPP syndrome. Both patients exhibited initial symptoms of inflammatory polyarthritis, accompanied by characteristic findings of "ghost cells" on skin biopsy. Additionally, radiographic and laboratory evidence revealed pancreatic changes consistent with this syndrome. This case series underscores the importance of multidisciplinary collaboration in managing PPP syndrome. Early recognition and accurate diagnosis are pivotal in initiating prompt and effective therapeutic interventions, thereby improving patient outcomes and minimizing long-term sequelae.
PubMed: 38826929
DOI: 10.7759/cureus.59471 -
European Journal of Radiology Oct 2023To analyze the computed tomography (CT) findings of idiopathic mesenteric panniculitis and the factors related to its characteristics and to improve the understanding of...
OBJECTIVES
To analyze the computed tomography (CT) findings of idiopathic mesenteric panniculitis and the factors related to its characteristics and to improve the understanding of the disease.
METHODS
The imaging findings of 121 patients with mesenteric panniculitis were retrospectively analyzed, along with related factors such as age, sex, and abdominal visceral fat area.
RESULTS
Among the 121 patients, two had midgut malrotation, and the lesions were located outside the mesentery on the right side of the abdominal cavity, while the lesions in the other patients were located around the mesentery on the left side of the abdominal cavity, presenting as patchy or patchy fuzzy high-density masses. Annulus fibrosus and/or fatty ring signs were also observed in some patients. Scattered soft tissue nodules were observed around the mesentery in 119 patients. Eight patients had intestinal tract traction and retraction, and one patient had secondary intestinal obstruction. Nearly half of the patients had mesenteric vascular changes, and three had mesenteric vascular thrombosis. Among the 121 patients, there were 89 males and 32 females, aged 22-83, with an average age of 52.14 ± 13.53 years. The distribution range of abdominal visceral fat area (VFA) in 121 patients was 79.85-331.65 cm.
CONCLUSION
Mesenteric panniculitis has certain characteristic imaging findings that can be accompanied by often ignored changes in the mesenteric blood vessels and intestinal tubes. Intestinal obstruction and mesenteric vascular thrombosis are rare complications, and their primary causes are often overlooked. Mesenteric panniculitis was correlated with sex, age, and VFA.
Topics: Female; Male; Humans; Adult; Middle Aged; Aged; Panniculitis, Peritoneal; Retrospective Studies; Intestinal Obstruction; Tomography, X-Ray Computed; Thrombosis
PubMed: 37666075
DOI: 10.1016/j.ejrad.2023.111071 -
Annals of Translational Medicine Mar 2021Dermatomyositis (DM) is a strikingly heterogenous disease characterized by a broad and ever-evolving spectrum of cutaneous manifestations that transcend the classic... (Review)
Review
Dermatomyositis (DM) is a strikingly heterogenous disease characterized by a broad and ever-evolving spectrum of cutaneous manifestations that transcend the classic "hallmarks" defined by Peter and Bohan in 1975. Despite the increasing preponderance and ubiquity of autoantibody, radiologic, and electrophysiologic testing, the diagnosis of DM still hinges largely on prompt detection of cutaneous manifestations of this condition. While pathognomonic cutaneous features of DM are more readily recognizable, many patients present with subtle and/or atypical skin manifestations, and diagnosis of DM may require clinician identification of these cutaneous clues. In this review, we highlight several of the lesser-known skin manifestations of DM, specifically, panniculitis, diffuse subcutaneous edema, erythroderma, calcinosis, ulceration, flagellate erythema, Wong-type DM, gingival telangiectasias, and the ovoid palatal patch. We describe the clinical and histopathologic presentation of these cutaneous findings. While manifesting less frequently than the heliotrope rash, Gottron's papules, and Gottron's sign, these cutaneous clues are equally important for clinicians to recognize in order to facilitate timely diagnosis and early intervention.
PubMed: 33842657
DOI: 10.21037/atm-20-5252 -
Frontiers in Immunology 2019Autoinflammatory diseases include disorders with a monogenic cause and also complex conditions associated to polygenic or multifactorial factors. An increased number of... (Review)
Review
Autoinflammatory diseases include disorders with a monogenic cause and also complex conditions associated to polygenic or multifactorial factors. An increased number of both monogenic and polygenic autoinflammatory conditions have been identified during the last years. Although skin manifestations are often predominant in monogenic autoinflammatory diseases, clinical and histopathological information regarding their dermatological involvement is still scarce. Monogenic autoinflammatory diseases with cutaneous expression can be classified based on the predominant lesion: (1) maculopapular rashes or inflammatory plaques; (2) urticarial rashes; (3) pustular, pyogenic or neutrophilic dermatosis-like rashes; (4) panniculitis or subcutaneous nodules; (5) vasculitis or vasculopathy; (6) hyperkeratotic lesions; (7) hyperpigmented lesions; (8) bullous lesions; and (9) aphthous lesions. By using this classification, this review intends to provide clinical and histopathological knowledge about cutaneous involvement in monogenic autoinflammatory diseases.
Topics: Autoimmune Diseases; Autoimmunity; Biomarkers; Biopsy; Dermatitis; Diagnosis, Differential; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Phenotype; Skin; Symptom Assessment
PubMed: 31736939
DOI: 10.3389/fimmu.2019.02448 -
Journal of Investigative Medicine High... 2024Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is... (Review)
Review
Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP.
Topics: Humans; Male; Biopsy; Diagnosis, Differential; Fatal Outcome; Lymphohistiocytosis, Hemophagocytic; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Panniculitis; Skin; Skin Neoplasms; Young Adult
PubMed: 38742532
DOI: 10.1177/23247096241253337