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Future Science OA 2024Non-melanoma skin cancers are more common in people with inflammatory bowel disease. However, these tumors can rarely mimic a cutaneous manifestation of the disease,...
Non-melanoma skin cancers are more common in people with inflammatory bowel disease. However, these tumors can rarely mimic a cutaneous manifestation of the disease, which delays diagnosis and clouds prognosis. A 35-year-old man with stenosing and fistulizing ileocolic Crohn's disease developed squamous cell carcinoma mimicking a groin fold abscess. After surgical drainage of the abscess, despite antibiotics and therapy combining azathioprine with infliximab, the abscess has recurred. Biopsies revealed a cutaneous squamous cell carcinoma. Palliative radiotherapy-chemotherapy was initiated, but the patient died after 3 months. This observation illustrates the increased risk of non-melanoma skin cancers in inflammatory bowel disease patients, particularly those exposed to thiopurines, and the value of diagnosing them at an early stage.
PubMed: 38827804
DOI: 10.2144/fsoa-2023-0109 -
Frontiers in Immunology 2024Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were...
BACKGROUND
Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance.
METHODS
IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method.
RESULTS
The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab.
CONCLUSION
Our findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.
Topics: Humans; Female; Immunoglobulin G; Male; Middle Aged; Aged; Autoantibodies; Cell Adhesion Molecules, Neuronal; HLA Antigens; Clinical Relevance
PubMed: 38827736
DOI: 10.3389/fimmu.2024.1376456 -
The American Journal of Case Reports Jun 2024BACKGROUND Antibodies against tumor necrosis factor alpha (anti-TNF-alpha) are currently widely used in the treatment of inflammatory bowel diseases (IBD), despite a...
BACKGROUND Antibodies against tumor necrosis factor alpha (anti-TNF-alpha) are currently widely used in the treatment of inflammatory bowel diseases (IBD), despite a number of reported adverse effects. Diverse neurologic syndromes, including the Guillain-Barre syndrome (GBS), an immune-mediated disease characterized by evolving ascending limb weakness, sensory loss, and areflexia, have been described in association with anti-TNF-alpha therapy. CASE REPORT A 45-year-old White woman was in follow-up with fistulizing ileocolonic Crohn disease using combination therapy (infliximab plus azathioprine) as CD maintenance therapy. After 3 years of this immunosuppressive therapy, she presented with symmetrical and ascending paresis in the lower limbs, and later in the upper limbs, in addition to reduced reflexes in the knees, 1 day after an infliximab infusion. The patient was hospitalized and treatment for CD was suspended. Neurophysiology studies demonstrated a pattern compatible with acute inflammatory demyelinating polyradiculopathy, with predominantly motor involvement, consistent with Guillain-Barre syndrome (GBS). Clinical, laboratory, and imaging exams were unremarkable. She was treated with intravenous immunoglobulins, with a progressive and complete resolution of neurological symptoms. After 1-year follow-up, she presented with active Crohn disease, and we opted for treating her with vedolizumab, with which she achieved clinical and endoscopic remission. CONCLUSIONS Patients receiving biological therapy with anti-TNF-alpha agents should be monitored for central or peripheral neurological signs and symptoms. The development of GBS can be secondary to anti-TNF-alpha treatment. The positive temporal relationship with TNF-alpha therapy and onset of neurological symptoms reinforces this possibility.
Topics: Humans; Guillain-Barre Syndrome; Female; Crohn Disease; Middle Aged; Infliximab; Tumor Necrosis Factor-alpha
PubMed: 38824385
DOI: 10.12659/AJCR.943709 -
Future Science OA 2024Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) are distinct liver diseases. Cases combining PBC and PSC, are...
Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) are distinct liver diseases. Cases combining PBC and PSC, are extremely rare. Here, we present a case of a 39-year-old woman with a history of colonic Crohn's disease treated with azathioprine. Discontinuation of the medication was prompted by abnormal liver function tests, but subsequent evaluations revealed persistent liver injury. Extensive diagnostic investigations, including imaging, serological tests, and liver biopsy, were conducted leading to a diagnosis of PBC-PSC overlap syndrome based on the presence of concentric lamellar fibrosis and chronic non-suppurative destructive cholangitis. The patient responded well to ursodeoxycholic acid treatment. This case emphasizes the importance of recognizing and diagnosing rare overlap syndromes, particularly those involving PBC and PSC, to ensure appropriate management and improve patient outcomes.
PubMed: 38817389
DOI: 10.2144/fsoa-2023-0187 -
Yonago Acta Medica May 2024We report the case of a 55-year-old female with eosinophilic granulomatosis with polyangiitis and chronic rhinosinusitis with nasal polyp. Rhinosinusitis recurred 6...
We report the case of a 55-year-old female with eosinophilic granulomatosis with polyangiitis and chronic rhinosinusitis with nasal polyp. Rhinosinusitis recurred 6 months after full-house endoscopic sinus surgery. Although conventional treatment with azathioprine and mepolizumab with steroids was given, it was difficult to simultaneously control both rhinosinusitis and eosinophilic granulomatosis with polyangiitis. Clinical examinations showed polyps in the olfactory cleft, and the patient's anosmia gradually became persistent. Even after administering mepolizumab for a certain period of time, symptoms did not improve, but when the biologic agent was switched to dupilumab, an improvement in recalcitrant chronic rhinosinusitis with nasal polyp was observed. While dupilumab was administered intermittently for refractory chronic rhinosinusitis with nasal polyp, the rhinosinusitis improved and symptoms such as worsening of eosinophilic granulomatosis with polyangiitis paresthesia were observed. Both symptoms gradually subsided 19 months after starting intermittent administration, leading to the discontinuation of dupilumab administration. Rhinosinusitis in the setting of eosinophilic granulomatosis with polyangiitis may be refractory in some cases, and this case provides findings demonstrating the strong effect of dupilumab on eosinophilic inflammation.
PubMed: 38803595
DOI: 10.33160/yam.2024.05.005 -
Multiple Sclerosis Journal -... 2024The use of non-specific immunosuppressants (NSIS) to treat multiple sclerosis (MS) remains prevalent in certain geographies despite safety concerns, likely due to...
BACKGROUND
The use of non-specific immunosuppressants (NSIS) to treat multiple sclerosis (MS) remains prevalent in certain geographies despite safety concerns, likely due to resource limitations.
OBJECTIVE
To use MSBase registry data to compare real-world outcomes in adults with relapsing-remitting MS (RRMS) treated with dimethyl fumarate (DMF) or NSIS (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mitoxantrone or mycophenolate mofetil) between January 1, 2014 and April 1, 2022.
METHODS
Treatment outcomes were compared using inverse probability of treatment weighting (IPTW) Cox regression. Outcomes were annualized relapse rates (ARRs), time to discontinuation, time to first relapse (TTFR) and time to 24-week confirmed disability progression (CDP) or 24-week confirmed disability improvement (CDI; in patients with baseline Expanded Disability Status Scale [EDSS] score ≥2).
RESULTS
After IPTW, ARR was similar for DMF (0.13) and NSIS (0.16; = 0.29). There was no difference in TTFR between cohorts (hazard ratio [HR]: 0.98; = 0.84). The DMF cohort experienced longer times to discontinuation (HR: 0.75; = 0.001) and CDP (HR: 0.53; = 0.001), and shorter time to CDI (HR: 1.99; < 0.008), versus the NSIS cohort.
CONCLUSION
This analysis supports the use of DMF to treat patients with relapsing forms of MS, and may have implications for MS practices in countries where NSIS are commonly used to treat RRMS.
PubMed: 38800132
DOI: 10.1177/20552173241247182 -
Canadian Journal of Kidney Health and... 2024Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by excessive immune activation. It is more commonly seen in children but...
RATIONALE
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by excessive immune activation. It is more commonly seen in children but increasingly recognized in adults. Primary HLH relies on a genetic predisposition, whereas secondary HLH develops in the context of infections, malignancies, or autoimmune diseases. Hemophagocytic lymphohistiocytosis has been rarely described in patients on immunosuppressive therapy after kidney transplant. Here, we describe a case of HLH in a patient with a remote history of kidney transplant, triggered by a viral infection.
PRESENTING CONCERNS
A 45-year-old female, with a kidney transplant in 2009 for IgA nephropathy, presented with fever, vomiting, and back pain of 1-week duration. She was on triple immunosuppression consisting of daily doses of prednisone 5 mg, azathioprine 100 mg, and tacrolimus extended release 1 mg, and a baseline creatinine of 130 µmol/L.
DIAGNOSIS
Initial investigations showed anemia, leukopenia, elevated serum creatinine, transaminitis, and markedly increased ferritin of 67 600 µg/L which prompted a bone marrow biopsy to rule out HLH. The bone marrow showed an increased proportion of CD68+ cells (macrophages) with more than 5 in 1000 hemophagocytic macrophages. Her soluble IL-2 receptor (CD25) level was 3406 pg/mL (606-2299 pg/mL) which was mildly elevated. She fulfilled 4 of the 8 criteria for HLH and with an H score was 223 which suggested a diagnosis of HLH with 96.9% probability. An extensive secondary workup for possible triggers for HLH led to a swab from genital ulcers that was positive for herpes simplex virus (HSV) type 2. The polymerase chain reaction (PCR) in the blood for HSV type 2 was also positive.
INTERVENTIONS
Given the diagnosis of HSV type 2 as the putative trigger for HLH, she was started on parenteral acyclovir for 2 weeks followed by oral valacyclovir for 2 more weeks. In the context of infection, the azathioprine was stopped while low-dose steroid and tacrolimus were continued.
OUTCOMES
With the initiation of treatment for HSV infection, leukopenia, creatinine, and transaminases improved along with ferritin levels. At her 6-month follow-up, her blood counts and liver enzymes had normalized, and ferritin was 566 µg/L.
TEACHING POINTS
Hemophagocytic lymphohistiocytosis is a rare disease in kidney transplant recipients with a high mortality rate. It can occur even in remote kidney transplant recipients so a high degree of suspicion is necessary to lead to a prompt diagnosis. Infections are common triggers for secondary HLH. Early identification and treatment of the triggering infection may improve outcomes.
PubMed: 38799982
DOI: 10.1177/20543581241253921 -
Clinical and Experimental... 2024Inflammatory bowel disease (IBD) affects young adults of reproductive age, and questions related to pregnancy and breastfeeding are common in clinical practice. Most...
BACKGROUND
Inflammatory bowel disease (IBD) affects young adults of reproductive age, and questions related to pregnancy and breastfeeding are common in clinical practice. Most medications used to treat IBD are considered safe during pregnancy, except methotrexate and small molecules such as tofacitinib. Despite few studies regarding vedolizumab (VDZ) safety, it appears to be safe during pregnancy. Therefore, this study aimed to report the management of ulcerative colitis in pregnant patient refractory to anti-tumor necrosis factor (TNF) agents using VDZ.
CASE REPORT
A female, 38 years old, with ulcerative colitis was refractory to conventional treatment with mesalazine, sulfasalazine, and azathioprine. She was hospitalized at six weeks of gestation with severe acute colitis requiring the use of infliximab (IFX) to induce remission. She had a spontaneous abortion at nine weeks of gestation after the second dose of IFX. Since there was no endoscopic improvement after six months of IFX treatment, VDZ treatment was initiated. During the VDZ infusion period, the patient discovered that she was pregnant with twins, leading to the discussion of the risks and benefits of continuing the VDZ. The patient presented with disease clinical remission with the use of VDZ, and the babies were born at 34 weeks of gestation without complications. Breastfeeding was also performed without complications.
CONCLUSION
Continued VDZ medication is safe during pregnancy and breastfeeding, with adverse events similar to anti-TNF therapy.
PubMed: 38799766
DOI: 10.2147/CEG.S457256 -
Clinical Case Reports Jun 2024Administering azathioprine or infliximab for UC and AS treatment carries a significant risk of adverse reactions. Here, we present the case diagnosed with UC and AS, who...
KEY CLINICAL MESSAGE
Administering azathioprine or infliximab for UC and AS treatment carries a significant risk of adverse reactions. Here, we present the case diagnosed with UC and AS, who received treatment with azathioprine and infliximab for 10 months, and subsequently developed drug-induced myopathy affecting the right vastus medialis muscle.
ABSTRACT
Drug-induced myopathy is an uncommon form of muscle injury that can arise in patients without preexisting muscle conditions when exposed to therapeutic doses of certain medications. Administering azathioprine or infliximab for ulcerative colitis (UC) and ankylosing spondylitis (AS) treatment carries a significant risk of adverse reactions, including drug-induced myopathy and increased susceptibility to opportunistic infections. However, occurrences of myopathy induced by the combination of azathioprine and infliximab are rarely reported in clinical practice. Here, we present the case of a 37-year-old male patient diagnosed with UC and AS, who received treatment with azathioprine and infliximab for 10 months. Despite the resolution of symptoms and improvement in intestinal mucosal inflammation observed via endoscopy, the patient subsequently developed drug-induced myopathy affecting the right vastus medialis muscle.
PubMed: 38799535
DOI: 10.1002/ccr3.8998 -
Biomedicines Apr 2024Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia....
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes.
PubMed: 38790929
DOI: 10.3390/biomedicines12050967