An update on the endocrine manifestations of antiphospholipid syndrome.

Antiphospholipid Syndrome (APS), characterized by hypercoagulability and pregnancy morbidity, poses a significant clinical challenge when involving organ systems, such as the endocrine system. APS can directly and indirectly influence the anterior and posterior lobes of the pituitary gland. The thyroid gland exhibits involvement, especially in patients with positive anticardiolipin antibodies, yet the clinical significance of the relationship with APS remains elusive. The pancreas, often overlooked, manifests in diverse ways, from pancreatitis to implications in diabetes. Adrenal insufficiency emerges as a common endocrine manifestation of APS, with adrenal hemorrhage or infarction being a presenting manifestation. Adrenal gland involvement has also been reported in the context of catastrophic APS. Pregnancy complications and infertility might be effects of APS on the female ovaries, while testicular torsion and decreased sperm concentration and total sperm count have been reported as rare effects of APS on male testes.

Adult-Onset Still's Disease Following COVID-19 Infection in a Patient Receiving Nirmatrelvir/Ritonavir: A Case Report.

SARS-CoV-2 (COVID-19) has been associated with numerous complications, including autoimmune and autoinflammatory diseases. The surge of cytokines following COVID-19 infection or vaccination has been proposed to contribute to immune dysregulation, which might subsequently give rise to an autoinflammatory syndrome. Adult-onset Still's disease (AOSD) is one of the rare autoinflammatory diseases characterized by a surge of cytokines. Although an association between COVID-19 vaccines and AOSD has been reported, an association with COVID-19 infection or nirmatrelvir/ritonavir remains very rare. In this case, we present a patient who developed AOSD after COVID-19 infection and subsequent treatment with nirmatrelvir/ritonavir. After the initial response to glucocorticoids, canakinumab was initiated, resulting in positive clinical outcomes.

Sarcoidosis as a cause of chronic back pain: a case report.

While sarcoidosis is typically a multisystem disease, it can, in some instances, exclusively affect the vertebrae, leading to back pain. Additionally, sarcoidosis may manifest with inflammation of the sacroiliac joints, not meeting the criteria for spondyloarthritis, yet contributing to back pain. In this report, we present a case involving a previously healthy 55-year-old woman who sought medical attention due to chronic back pain. She was subsequently diagnosed with spinal sarcoidosis, based on MRI, PET scan, and biopsy results. Furthermore, treatment with prednisolone monotherapy demonstrated substantial improvement in her symptoms.

Refractory Adult-onset Still's Disease Treated with a Combination of Methotrexate and Etanercept.

BACKGROUND: Adult-onset Still's disease (AOSD) is a challenging diagnosis because of the variability in clinical presentation and lack of gold-standard diagnostic investigations. Even after diagnosis, the treatment is challenging, especially when the disease is refractory to first-line therapy. Multiple pharmacotherapeutic options exist for refractory AOSD, but treatment failures still occur. Etanercept, a Tumor necrosis factor (TNF)-alpha inhibitor, is one of the options that has been rarely used for refractory AOSD, with various outcomes ranging from no response to complete remission. CASE PRESENTATION: In this case, we highlight how a previously healthy lady had refractory AOSD to glucocorticoids, methotrexate, and hydroxychloroquine combination therapy. There was no response to interleukin (IL)-1 therapy, which necessitated a switch to a combination of etanercept, low-dose methotrexate, and low-dose glucocorticoids with complete remission for a total of three- -year follow-up. CONCLUSION: The combination of methotrexate and Etanercept can maintain remission in patients with refractory AOSD.

Vacuolar Interface Dermatitis as a Histologic Reaction Pattern of Sjögren's Syndrome: A Case Report.

Sjögren's syndrome (SS) has been widely known for its dry mouth and dry eyes presentation. Extraglandular disease manifestations may be protean and pose a challenge for clinicians, especially when the typical known manifestations are absent. Skin involvement of SS is variable, and cutaneous signs and symptoms may be the initial presentation of this syndrome. Vacuolar interface dermatitis has been linked to dermatomyositis and systemic lupus erythematosus, but rarely to SS. Herein, we present the case of an 87-year-old man who presented for widespread itchy erythematous scaly plaques that were refractory to topical corticosteroids as well as discontinuation of possible offending medications. A biopsy demonstrated vacuolar interface dermatitis in the setting of strongly positive anti-SSA. Hydroxychloroquine treatment was effective in resolving the plaques.

Sarcoidosis Mimicking a Malignant Metastatic Disease.

Sarcoidosis can have pulmonary and extrapulmonary clinical manifestations depending on the organ of involvement. Because multiple organs are involved by the disease, sarcoid can mimic metastatic diseases. Whenever clinical and radiological clues of metastasis are present, differentials other than cancer should not be missed. Herein, we present a case of a middle aged gentleman who presented to the oncology clinic for 1-month history of low back pain associated with a dry cough along with radiological findings of metastatic disease involving the lungs, liver, lymph nodes, axial spine, and adrenal gland. A biopsy of the liver lesion showed non-caseating granuloma. Elevated blood levels of angiotensin-converting enzyme confirmed the diagnosis of sarcoidosis.

Pseudomonas putida bacteremia secondary to a soft tissue wound: A case report.

Pseudomonas putida is an uncommon cause of bacteremia, that usually seeds from multiple sources including soft tissues. Immunocompromised states predispose patients to fulminant infections, and sometimes death. Broad-spectrum antibiotics, such as fourth-generation cephalosporins, are usually indicated for treatment. Herein, we present a 71-year-old gentleman with fever and left leg swelling, found to have P. putida bacteremia. Intravenous (IV) ceftazidime was initiated, yielding clearance of blood cultures and clinical improvement.

Lupus, antiphospholipid syndrome, and stroke: An attempt to crossmatch.

Cerebrovascular accidents (CVAs) or strokes are part of the common thrombotic manifestations of Systemic Lupus Erythematosus (SLEs) and Antiphospholipid syndrome (APS). Such neurological thrombotic events tend to occur in patients with SLE at a higher frequency when Antiphospholipid antibodies (aPLs) are present, and tend to involve the large cerebral vessels. The mechanism of stroke in SLE can be driven by complement deposition and neuroinflammation involving the blood-brain barrier although the traditional cardiovascular risk factors remain major contributing factors. Primary prevention with antiplatelet therapy and disease activity controlling agent is the basis of the management. Anticoagulation via warfarin had been a tool for secondary prevention, especially in stroke recurrence, although the debate continues regarding the target international normalized ratio (INR). The presence of either of the three criteria antiphospholipid antibodies (aPLs) and certain non-criteria aPL can be an independent risk factor for stroke. The exact mechanism for the involvement of the large cerebral arteries, especially in lupus anticoagulant (LAC) positive cases, is still to be deciphered. The data on the role of non-criteria aPL remain very limited and heterogenous, but IgA antibodies against ß2GPI and the D4/5 subunit as well as aPS/PT IgG might have a contribution. Anticoagulation with warfarin has been recommended although the optimal dosing or the utility of combination with antiplatelet agents is still unknown. Minimal data is available for direct oral anticoagulants (DOACs).

Erythema nodosum in Behçet's disease in remission: Think COVID-19?

The coronavirus disease has several manifestations related to the activation of the immune system. Because of such activation, autoimmune diseases, including vasculitis, have been reported to occur. Behçet's disease, a variable vessel vasculitis, has been discussed in the context of coronavirus disease. Rarely, the induction of Behçet's disease flare or exacerbation has been reported necessitating aggressive treatment. The presentation of Behçet's disease flares secondary to coronavirus disease is variable, including mucocutaneous lesions and eye or joint involvement. We highlight the case of a 35-year-old woman with pre-existing Behçet's disease in remission on colchicine presenting with new onset erythema nodosum-like lesions on her right shin being diagnosed with coronavirus disease infection a few days after. Despite treatment with systemic corticosteroid, the lesions did not resolve, necessitating the initiation of anti-interleukin-6 therapy.

ANCA-Associated Vasculitis following the First Dose of Pfizer-BioNTech COVID-19 Vaccine.

Coronavirus disease (COVID-19) vaccine can alter the body's immunological balance leading to autoimmune disease in rare cases. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of the autoimmune diseases which have been rarely reported to appear post-COVID-19 vaccine. Herein, we report the case of a 47-year-old woman who developed acute renal failure few days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. Corticosteroids along with azathioprine were used for the management.

Role of pro-inflammatory interleukins in osteoarthritis: a narrative review.

PURPOSE: This manuscript will summarize the role of pro-inflammatory cytokines and tackle newly discussed ones within the scope of OA pathogenesis as mentioned in the recent literature. This will allow for a better understanding of the mechanisms behind such a complicated disease. MATERIAL AND METHODS: Relevant articles were obtained by searching key terms including "pro-inflammatory cytokines," "inflammation," "pathophysiology," "cartilage damage," and "OA" in PubMed and Google Scholar databases. The year ranges set for the selection of the articles was between 2015 -2021. Inclusion criteria was based on the relevance and contribution to the field of the study. RESULTS: Osteoarthritis (OA) has a complex multifactorial pathophysiology which is attributed to molecular and biomechanical changes that disrupt the normal balance of synthesis and degradation of articular cartilage and subchondral bone. Pro-inflammatory cytokines, with their wide range of action and intricate signaling pathways, are the constant subject of new discoveries revolving around this inflammatory disease. The available literature indicates that some of these cytokines such as IL-33, IL-17, IL-6, and IL-22 have a direct relation to cartilage degradation, while others like IL-15, IL-1, IL-7, and IL-34 have an indirect one. CONCLUSIONS: Inflammation has an essential role in the manifestation of osteoarthritis clinical events. Specifically, certain cytokines exhibit pro-inflammatory properties that are markedly activated during the course of the disease and notably alter the homeostasis of the joint environment. However, clinical trials and observational studies remain insufficient to navigate the varying nature of this disease in humans.

Hematological manifestations of antiphospholipid syndrome: Going beyond thrombosis.

Thrombotic complications are a hallmark of antiphospholipid syndrome (APS). These vascular - arterial, venous, and/or small vessel - complications are well described and known to hematologists and healthcare providers caring for patients with this disease. In this review, we shed light on other hematological manifestations of the disease, including bleeding, thrombocytopenia, autoimmune hemolytic anemia, and thrombotic microangiopathy syndromes. While these manifestations are not bona fide clinical criteria for the diagnosis of APS, they frequently interact and contribute to the complexity of clinical management of APS.

The psychological impact of Behçet's disease.

BACKGROUND: Bechet's disease (BD), a chronic multiorgan involving disease, has a significant impact on quality of life in spite of effective treatment modalities. Disease manifestations such as arthritis, orogenital ulcerations, rashes, angiitis, and neurological involvement affect health-related quality of life (HRQoL) through its impact on depression, anxiety, and fatigue. OBJECTIVES: We aimed explore the psychological impact of BD, taking into consideration the effect on the HRQoL, as well as the association with depression, anxiety, wellbeing, and fatigue. METHODS: This is a narrative review of the literature that looks into the association of BD on the HRQoL including all studies that have assessed such as association. RESULTS/FINDINGS: Depression and anxiety are prevalent among patients with BD, and contribute significantly to fatigue, a common symptom among BD patients. In addition, the psychological wellbeing is affected by the disease, however, more studies are needed to assess this relationship. CONCLUSION: Depression and anxiety are strongly associated with BD, and contribute significantly to fatigue, a common symptom among BD patients. In addition, the psychological wellbeing is affected by the disease, however, more studies are needed to assess this relationship. Besides, the controlling factors of the psychological impact are still to be deciphered.

Rheumatoid Cerebral Vasculitis in a Patient in Remission.

Cerebral vasculitis is a very rare extra-articular complication of rheumatoid arthritis (RA) that is often challenging to diagnose. Elevated titers of rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), and antinuclear antibodies (ANA) have been linked with severe complications. The absence of highly elevated titers of RF, anti-CCP, and ANA can complicate the diagnosis of RA-associated cerebral vasculitis. We report the case of a 59-year-old woman with long-standing arthritis maintained on rituximab and leflunomide who developed sudden headaches and altered level of consciousness. Laboratory work-up revealed normal lymphocyte count and mildly elevated total serum protein and anti-CCP with negative RF and ANA and no evidence for viral or bacterial infections. Cerebrospinal fluid analysis (CSF) showed slightly elevated anti-CCP with normal levels of CXCL-13 and interleukin 6 (IL-6). Brain magnetic resonance imaging (MRI) showed ill-defined lesion of high T2 signal. Using MR angiogram, MR perfusion, and MR spectroscopy, the diagnosis of rheumatoid cerebral vasculitis was confirmed. The patient was treated with intravenous methyl-prednisolone with fast complete improvement. We conclude that adequate immunosuppression in RA might not be able to prevent rare extra-articular manifestations such as rheumatoid cerebral vasculitis.

Thalassemia and autoimmune diseases: Absence of evidence or evidence of absence?

The thalassemias are a group of inherited disorders of hemoglobin synthesis that continue to pause a global public health concern. The complex molecular and pathogenetic pathways involved in disease process lead to an array of comorbidities that require lifelong management. The disease and its treatment can also lead to alterations in immune function and a link to various autoimmune diseases has been frequently suggested. However, most data stem from single case reports and small studies that do not allow proper assessment of causal associations. Still, the high morbidity in thalassemia makes patients vulnerable to the added burden of coexisting autoimmune diseases, and special management considerations in this patient population are warranted. In this review, we explore insights and data from the literature on various autoimmune disease that have been observed in patients with thalassemia. The role of the thalassemia carrier state in modifying outcomes of patients with autoimmune diseases is also discussed.

Clinical burden of hemophilia in older adults: Beyond bleeding risk.

The prospect of hemophilia patients has dramatically improved in the last few decades with the introduction of various interventions that can effectively treat or prevent their bleeding risk. The life expectancy of patients can now reach that of the healthy population, but this has paved the way for several previously unrecognized morbidities to manifest in older adults with hemophilia. Such clinical complications are attributed to suboptimal management or poor access to effective therapy during childhood as well as chronicity and prolonged exposure to the underlying pathophysiology of the disease and its treatment. Complications common in the aging population are also becoming increasingly relevant in this vulnerable patient subgroup. In this review, we highlight peculiarities of such morbidities including chronic viral infections and liver disease, debilitating joint impairment and bone disease, cardiovascular and chronic kidney disease, and cancers. We also reflect on topics of special interest in adulthood such as sexuality.

COVID-19 and antiphospholipid antibodies: A position statement and management guidance from AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION).

Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.

I drank too much and now I can't walk: a case of alcohol-induced dysautonomia.

Dysautonomia is a dysfunction of the autonomic nervous system, which mediates both sympathetic and parasympathetic functions of the human body. Alcohol has been established to affect the autonomic function through liver injury and accumulation of vasodilators. Alcohol can induce peripheral neurological diseases as well. This case report describes a patient who had a chronic history of alcoholism and uncontrolled diabetes mellitus presenting for orthostatic hypotension and peripheral neuropathy without underlying liver disease or other endocrinopathies. Although diabetes mellitus was controlled pharmacologically and risk factors for orthostatic hypotension were managed conservatively, his symptoms did not improve which indicated an alcohol-related autonomic dysfunction, shedding light on one of long-term complications of alcoholism.