Search Results (330)

The increasing consumption of pharmaceuticals associated with global population growth has intensified concerns regarding their release into aquatic environments and potential ecotoxicological effects. In this context, this study evaluated the ecotoxicity and biodegradation of the widely used corticosteroid prednisone. Ecotoxicity assays were performed using aquatic organisms representing different trophic levels: Artemia salina (microcrustacean), Aliivibrio fischeri (marine bacterium), and the cyanobacterium Microcystis novacekii. Biodegradation assays were conducted using M. novacekii. Prednisone was tested at concentrations ranging from 5 to 100 mg/L, corresponding to its maximum solubility in water. All experiments were carried out in accordance with standardized protocols (ABNT NBR 16530, ABNT NBR 15411-3, ISO 11348-3, and OECD 201). No toxic effects were observed for prednisone in any of the tested organisms, as responses at all tested concentrations, including the highest, were not significantly different from the control. Therefore, it was not possible to estimate EC50 values within the tested concentration range. According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), substances with effect concentrations above 100 mg/L are considered non-toxic to aquatic organisms. During biodegradation assays, a reduction in prednisone concentration was observed during the growth of M. novacekii, which was associated with an increase in the pH of the culture medium. These results suggest that prednisone degradation occurred indirectly through pH changes caused by cyanobacterial growth rather than through direct metabolic pathways. Full article

Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated autoimmune diseases. Case presentation. We present the case of a female patient diagnosed at the age of 10 with ASC, for which immunosuppressive therapy with prednisone, azathioprine (AZA), and ursodeoxycholic acid (UDCA) was initiated, with an initially favorable course. One year later, following a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, the patient experienced reactivation of liver disease and subsequently developed ulcerative pancolitis (UC), for which 5-aminosalicylic acid (5-ASA) therapy was initiated. Due to repeated hepatic flares and/or colitis relapses, therapy was escalated successively to mycophenolate mofetil, tacrolimus, and eventually infliximab (IFX). Despite treatment, the liver disease progressed, culminating in liver cirrhosis. Our patient developed portal hypertension and esophageal varices, with two episodes of upper gastrointestinal bleeding requiring endoscopic band ligation. At the age of 14, the patient developed recurrent episodes of non-infectious ulcerative stomatitis. Biopsy of the lesions revealed non-specific chronic inflammation, unrelated to colitis activity (confirmed microscopic remission of UC). By exclusion, an adverse drug reaction was suspected, with AZA being the most likely cause. Following its discontinuation, the lesions resolved. Beyond the physiological and therapeutic aspects, the patient displays marked emotional fragility due to prolonged and repeated hospitalizations (18 out of 60 months), which have impacted treatment adherence. Conclusions. This case highlights the complexity of managing pediatric patients with multiple autoimmune diseases. The necessary combination of immunosuppressive therapies may lead to significant adverse effects and further complicate disease progression. Moreover, psychological components play a crucial role in treatment compliance and therapeutic success, emphasizing the need for an integrated approach that includes specialized psychological support. Full article

Background: Systemic lupus erythematosus (SLE) may present with heterogeneous clinical manifestations in pediatric patients. Although infections are a major cause of morbidity and mortality in SLE, severe bacterial infections rarely represent the presenting clinical event leading to diagnosis. Case description: We report the case of a 13-year-old boy diagnosed with SLE with Sjögren’s syndrome overlap who presented with pneumococcal sepsis. The patient was admitted with high-grade fever and facial swelling, and blood cultures grew Streptococcus pneumoniae. Although an initial clinical response to antibiotic therapy was observed, fever subsequently recurred, accompanied by persistent systemic symptoms and progressive laboratory abnormalities. Further investigations revealed hematologic abnormalities, serosal involvement, renal disease, and a characteristic autoantibody profile. The patient fulfilled the 2019 ACR/EULAR classification criteria for SLE after comprehensive autoimmune evaluation. The overlap with Sjögren’s syndrome was supported by the autoantibody profile and imaging findings involving the parotid glands. Following treatment with intravenous methylprednisolone pulses, oral prednisone, hydroxychloroquine, and mycophenolate mofetil, the patient showed rapid clinical improvement and sustained remission. Conclusions: This case highlights that severe invasive bacterial infection may occasionally be the clinical circumstance that leads to the diagnosis of pediatric systemic lupus erythematosus. Persistent systemic inflammation or evolving multisystem involvement despite appropriate antimicrobial therapy should prompt consideration of an underlying autoimmune disease, even in patients without a prior history of immune dysfunction. Full article

Steroid hormones (SHs) have a high estrogenic potential, and urban wastewater is one of their main ways into the aquatic environment. Constructed wetlands (CWs) are considered one of the most sustainable alternatives for the treatment of wastewater from small communities. However, the use of gravel and sand implies a significant environmental impact associated with their extraction and transport. A more sustainable alternative is the use of plant residues, as they are abundant, inexpensive, and readily available, and they can improve the efficiency of hormone removal through sorption. Thus, the sorption of 15 SHs was studied on conventional, mineral substrates (gravel, sand, and volcanic ash) and alternative vegetal wastes, i.e., mulches from giant reed, palm tree, balsa wood, and pine needles. These materials were characterized by determining their Point of Zero Charge (pH_PZC), ash content, content of leachable polycyclic aromatic hydrocarbons (PAH) and heavy metals, total surface area (BET), and pore characteristics. Results indicated that SH sorption on the mineral substrates was quite low, in most cases less than 10–15%. However, in the mulches it reached between 50 and 95%, except for corticosteroids (11–43%). The pseudo-second-order kinetics provided the best fit in all cases, with R² values between 0.97 and 0.9999. Experiments with a contact time of 7 days showed that the palm tree was the only substrate that completely removed the three corticosteroids studied (cortisone, prednisone, and prednisolone). Additionally, a significant correlation was observed between removal due to sorption (%) and log octanol–water partition coefficient (log Kow). Freundlich isotherm provided a higher number of best fits than Langmuir. Lastly, to compare sand with palm mulch under more realistic experimental conditions, four lab-scale CWs (two with palm mulch and two with sand, with/without plants) were studied. The sand-based CWs achieved faster SH percentage removals, while after 24 h, SH mass removals were significantly higher in the palm mulch-based CWs. Full article

Background: Rapidly progressive glomerulonephritis (RPGN) is a severe nephrological emergency, frequently secondary to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. In older adults, the coexistence of comorbidities and monoclonal gammopathy of undetermined significance (MGUS) makes it difficult to distinguish between ANCA vasculitis and monoclonal gammopathy of renal significance (MGRS), which differ in prognosis and treatment. The coexistence of PR3-ANCA-associated vasculitis and MGUS is uncommon and sparsely documented. Case Presentation: A 72-year-old woman with hypertension and type 2 diabetes presented with acute deterioration and rapidly progressive renal failure, requiring hemodialysis. She had subnephrotic proteinuria, hematuria, and an active urinary sediment. The autoimmune workup showed ANCA negativity using immunofluorescence, but PR3-ANCA positivity using ELISA. Hematologic characterization documented an IgG kappa monoclonal spike; no bone lesions, amyloidosis, or criteria for multiple myeloma were found; and the patient was classified as MGUS. Renal biopsy revealed necrotizing extracapillary pauci-immune glomerulonephritis with cellular and fibrocellular crescents and no monoclonal deposits, consistent with PR3-ANCA vasculitis. Induction therapy with methylprednisolone pulses and oral prednisone was initiated; cyclophosphamide was not administered because of catheter-associated Staphylococcus aureus bacteremia and upper gastrointestinal bleeding complicated by disseminated intravascular coagulation. The patient died on day 25 due to infectious and hemorrhagic complications. Conclusions: This case provides additional documentation of an uncommon overlap between PR3-ANCA-associated vasculitis and MGUS in a Latin American patient and highlights the role of renal biopsy in distinguishing MGRS from pauci-immune vasculitis in the presence of paraproteinemia. It also underscores the need to tailor immunosuppression in frail older adults, balancing disease control against the risk of severe infection. Full article

Cerebral toxoplasmosis is a rare but potentially fatal opportunistic infection in renal transplant recipients receiving long-term immunosuppressive therapy. It may result from donor-derived transmission or reactivation of latent infection. We report the case of a 70-year-old female who underwent kidney transplantation from a deceased donor in 2004 for end-stage renal disease due to glomerulonephritis. She was maintained on cyclosporine, mycophenolate mofetil, and prednisone. In September 2024, she presented with headache, mood changes, and right-sided hemiparesis. Brain multislice computed tomography revealed a large temporoparietal lesion initially suspected to be glioblastoma. Craniotomy and histopathological analysis demonstrated encysted Toxoplasma gondii bradyzoites within gliotic tissue. Polymerase chain reaction testing confirmed the presence of T. gondii DNA, while human immunodeficiency virus testing was negative. The patient reported frequent contact with domestic cats. Treatment with pyrimethamine, sulfadiazine, and leucovorin, alongside adjustment of immunosuppressive therapy, led to marked neurological improvement and radiological regression of the lesion. However, nine months later, she succumbed to multidrug-resistant urosepsis. This case highlights the diagnostic challenges of cerebral toxoplasmosis in transplant recipients, as radiological findings are often nonspecific and can mimic neoplastic or lymphoproliferative lesions. Polymerase chain reaction and histopathological analysis remain essential for definitive diagnosis. Awareness of this rare complication is critical for early recognition and prompt initiation of anti-toxoplasma therapy, which can significantly improve outcomes. Although cerebral toxoplasmosis is uncommon after kidney transplantation, it should be considered in immunosuppressed patients presenting with neurological symptoms. Early detection and targeted therapy are key to reducing morbidity and mortality in this population. Full article

COVID-19 mRNA vaccines activate type I interferon pathways and in genetically or immunologically predisposed individuals may trigger autoimmune responses, including autoantibodies against melanoma differentiation-associated protein 5 (MDA5). Although cases of dermatomyositis (DM), particularly anti-MDA5-positive DM, have been increasingly reported after SARS-CoV-2 vaccination, its clinical spectrum and management remain incompletely defined. We conducted a narrative review of the literature on post-vaccination dermatomyositis, focusing on clinical features, autoantibody profiles, therapeutic approaches, and outcomes. The review was enriched by the inclusion of a new case: a 60-year-old woman who developed anti-MDA5-positive dermatomyositis two weeks after receiving her fourth dose of the BNT162b2 (Pfizer/BioNTech) vaccine. She presented predominantly with cutaneous and articular manifestations in the absence of interstitial lung disease. Treatment with oral prednisone, intravenous alprostadil, and the Janus kinase inhibitor tofacitinib resulted in marked clinical improvement. This case, together with the literature review, illustrates both typical and atypical presentations of vaccine-associated anti-MDA5 DM, highlights diagnostic challenges without lung involvement, and suggests JAK inhibition as a potential therapeutic option, contributing to a more comprehensive understanding of post-vaccination dermatomyositis. Full article

Background: IgG4-related hypertrophic pachymeningitis (IgG4-RHP) is an extremely rare central nervous system (CNS) autoimmune disorder, characterized by dural thickening, space-occupying effects, and neurological compression symptoms. It is frequently misdiagnosed as meningioma due to overlapping radiological features, leading to inappropriate management. This study aims to report a unique case of IgG4-RHP with skull destruction and subcutaneous mass formation, and summarize its diagnostic and therapeutic strategies through literature review. Methods: A 53-year-old male with a chronic subdural hematoma history was admitted for a progressive right frontal subcutaneous mass. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) were performed, followed by staged surgeries (subcutaneous biopsy and craniotomy with subtotal resection). Histopathological examinations (Hematoxylin and Eosin staining, IgG/IgG4 immunostaining) and serum IgG4 detection were conducted. The patient received postoperative prednisone acetate (60 mg/d) and 3-month follow-up. A literature search was also performed to analyze 34 previously reported IgG4-RHP cases. Results: Histopathology showed dense lymphoplasmacytic infiltration, storiform fibrosis, ≈40 IgG4+ plasma cells per high-power field (HPF), and an IgG4+/IgG+ ratio of ≈30%. Serum IgG4 was significantly elevated to 1521 μg/mL (normal < 1350 μg/mL), with marked reduction in residual lesions on follow-up MRI. Literature review revealed a 73.5% male predominance, mean age of 48.6 years, headache as the most common symptom (58.8%), and a 38.5% misdiagnosis rate. Glucocorticoids alone or combined with immunosuppressants achieved favorable outcomes in 96.0% of treated cases. Conclusions: Histopathological examination combined with serum IgG4 detection is the gold standard for IgG4-RHP diagnosis. Surgical resection relieves mass-occupying effects, while glucocorticoids are first-line therapy. Long-term follow-up is necessary for recurrence monitoring, and rituximab is effective for refractory cases. Awareness of atypical manifestations like skull destruction can reduce misdiagnosis and improve outcomes. Full article

A 75-year-old male was admitted with worsening anemia and spontaneous bruising in the left abdominal wall and paraspinal region. Laboratory workup revealed low factor XIII (FXIII) activity levels. Cryoprecipitate transfusions raised his FXIII level, but still fluctuated drastically, ranging from 4 to 43% was discharged 3 days later once his bleeding was managed. Three days later, he was readmitted for severe pain and new bruising in his latissimus dorsi and lateral right thigh. CT-scan revealed hemothorax and arterial bleeding requiring an urgent angiogram with embolization. Chromogenic and functional FXIII assays were unable to elucidate an inhibitor at this time. Management included FXIII concentrate, rituximab, and prednisone; the patient was discharged 12 days later with FXIII levels of 50%. After prednisone tapering, FXIII levels decreased drastically. This case exemplified that higher levels of FXIII are required to prevent bleeding diatheses rather than the previously reported minimum of 5% activity. Despite the diagnostic uncertainty of laboratory testing, the shortened half-life of FXIII activity following replacement therapy and favorable response to immunotherapy indicates that the bleeding diathesis was caused by an acquired inhibitor. Full article

Background and Objectives: IgG4-related disease is a chronic fibro-inflammatory condition. Despite the development of classification and responder indexes, reliable biomarkers for disease activity and therapeutic monitoring remain limited. We evaluate the performance of a panel of biomarkers, including cytokine profiles, plasmablasts and conventional markers. Materials and Methods: We conducted a cross-sectional, single-center study, involving 35 patients diagnosed with IgG4-RD. Disease activity was evaluated using the IgG4-RD Responder Index (RI), Damage Index (DI) and clinical assessment. Laboratory evaluation included serum IgG4, total IgG, CRP, ESR, eosinophils, IgE, complement levels, and cytokine profiling via multiplex immunoassay. B cell subpopulations were analyzed by flow cytometry. Statistical analyses were performed using STATA/BE 17.0. Results: Patients with active disease (RI > 4 or clinical judgment) exhibited significantly higher levels of total IgG (p = 0.02), IgG4 (p = 0.01), and IL-5 (p = 0.03). PET-positive patients showed a Th1-skewed immune profile, with elevated IFN-γ/IL-4 (p < 0.001), reduced IL-21/IFN-γ (p = 0.03), and increased eosinophils (p = 0.03). Clinician-assessed active disease was associated with higher total IgG levels (p = 0.01). Treatment-specific effects were observed: prednisone was associated with lower IgG4 and C3 levels. Notably, plasmablasts did not consistently correlate with clinical or imaging activity scores, possibly reflecting treatment status or B cell dynamics. Conclusions: This study demonstrates that cytokine ratios, particularly those involving IL-5, IL-13, IL-21, and IFN-γ, offer complementary information to traditional serological markers for IgG4-RD activity. While PET/CT-defined activity was best reflected by biomarkers of an IFN-γ-mediated pathway, the IgG4-RD RI demonstrated a stronger association with conventional humoral markers like serum IgG4 and total IgG. None of these biomarkers correlated with organ damage. Full article

Background: Comparative real-world data on the pharmacokinetics of once-daily tacrolimus formulations in de novo kidney transplantation remain limited. We compared tacrolimus exposure and dosing requirements with Envarsus and Advagraf during the early post-transplant period. Methods: We conducted a prospective, observational, single-center study including adult de novo kidney transplant recipients treated with once-daily tacrolimus as either Envarsus or Advagraf. The immunosuppressive protocol was based on thymoglobulin induction, with delayed initiation of tacrolimus at an initial dose of 0.15 mg/kg/day, prednisone, and sirolimus as the third immunosuppressive agent. Trough concentrations (C0), daily dose, and dose-normalized trough exposure (C0/D) were assessed at 48 h and over 3 months (days 7, 14, 30, 60, and 90). Dose adjustments were guided by therapeutic drug monitoring and Bayesian individualization to achieve target trough ranges (6–10 ng/mL during month 1; 5–7 ng/mL thereafter). Clinical effectiveness and safety outcomes were evaluated through month 3. Results: Ninety recipients were included (Advagraf n = 43; Envarsus n = 47). At 48 h, Envarsus achieved higher trough concentrations and higher C0/D than Advagraf (C0: 10.7 vs. 7.7 ng/mL; C0/D: 1.30 vs. 0.75 (ng/mL)/mg; both p < 0.001). From week 1 to month 3, trough concentrations were similar between groups (week 1: 8.5 vs. 8.5 ng/mL, p = 0.968; month 3: 5.7 vs. 5.1 ng/mL, p = 0.234), but Envarsus required lower daily doses (week 1: 6.4 vs. 9.9 mg/day, p = 0.001; month 3: 3.2 vs. 4.1 mg/day, p = 0.021) and maintained higher C0/D (week 1: 1.53 vs. 1.00, p = 0.001; month 3: 1.94 vs. 1.57 (ng/mL)/mg, p = 0.012). At 48 h, infra-therapeutic troughs were less frequent with Envarsus (6.7% vs. 40.5%, p = 0.0001), while supra-therapeutic levels were more frequent (57.8% vs. 18.9%), and tacrolimus discontinuation due to high troughs occurred more often (23.4% vs. 7.0%, p = 0.032). Over 3 months, the proportion of measurements within the therapeutic range was similar (57.6% vs. 64.5%, p = 0.705). Efficacy and safety were similar between groups. Conclusions: In de novo kidney transplant recipients, Envarsus provides higher early tacrolimus exposure and consistently higher dose-normalized trough exposure than Advagraf, enabling lower maintenance doses while maintaining similar short-term effectiveness and safety. However, early overexposure was more frequent with Envarsus at 0.15 mg/kg/day, supporting careful early monitoring and consideration of lower starting doses. Full article

Primary effusion-based lymphomas are uncommon and may pose significant diagnostic challenges. Fluid overload-associated large B-cell lymphoma is a recently recognized entity in the 5th edition of the World Health Organization Classification of Hematolymphoid Tumors and should be included in the differential diagnosis of effusion-based lymphomas, particularly in elderly immunocompetent patients with conditions that predispose to fluid overload. Background and Clinical Significance: We report a case of fluid overload-associated large B-cell lymphoma to add to the limited literature and highlight distinguishing features from other primary effusion lymphomas. Case Presentation: A 77-year-old male with end-stage renal disease on hemodialysis and heart failure with reduced ejection fraction was admitted for respiratory failure and found to have a right-sided pleural effusion. Two pleural fluid specimens examined several weeks apart revealed sheets of large atypical lymphoid cells positive for CD20, Pax-5, CD79a, CD45, MUM1, BCL2, BCL6 (weak) and negative for TTF1, CD68, MOC31, BER EP4, WT1, Calretinin, CD3, CD138, CD30, and cMYC. Human Herpesvirus-8 and Epstein–Barr virus were negative. Staging showed a few mildly fluorodeoxyglucose-avid mediastinal lymph nodes which were benign. Ultimately, the patient was diagnosed with fluid overload-associated large B-cell lymphoma and treated with rituximab, cyclophosphamide, vincristine sulfate, and prednisone, but passed away three months after diagnosis. Conclusions: Fluid overload-associated large B-cell lymphoma is a new and important diagnostic consideration in effusion-based lymphomas. It may be mistaken for other conditions such as primary effusion lymphoma or other diffuse large B-cell lymphomas. The presence of a Human Herpesvirus-8-negative effusion-based lymphoma in an elderly immunocompetent patient without nodal or tissue involvement should prompt consideration of fluid overload-associated large B-cell lymphoma. Full article

Background and Clinical Significance: Mantle cell lymphoma (MCL) frequently involves bone marrow, gastrointestinal tract, and hepatosplenomegaly, whereas pleural effusions are uncommon. Cases requiring invasive mechanical ventilation and thoracic drainage are rare. We report a case of MCL with persistent massive pleural effusions requiring invasive mechanical ventilation and bilateral continuous thoracic drainage. Case Presentation: A 71-year-old woman presented with dyspnea and was found to have bilateral pleural effusions and generalized lymphadenopathy. Shortly after admission, she developed acute respiratory failure due to pleural effusions and required invasive mechanical ventilation. Right-sided continuous thoracic drainage was initiated. Thereafter, more than 1 L of pleural fluid was drained each day. Flow cytometry of the pleural fluid showed CD5-positive B cells with kappa light-chain restriction. Bone marrow examination revealed abnormal lymphocyte infiltration. Cervical lymph node biopsy demonstrated diffuse proliferation of medium-sized, abnormal B lymphocytes with an immunophenotype of CD5⁺, CD19⁺, CD20⁺, cyclin D1⁺, SOX11⁺, and κ⁺, with a Ki-67 index of 20%, confirming MCL, stage IV. Immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was commenced under mechanical ventilation. Shortly thereafter, left-sided continuous thoracic drainage was also initiated. However, in response to immunochemotherapy, the bilateral pleural effusions gradually subsided, enabling extubation, and there was no reaccumulation after removal of both chest tubes. Furthermore, generalized lymphadenopathy regressed, and bone marrow examination revealed resolution of lymphoma infiltration, resulting in complete remission. Conclusions: De novo MCL complicated by persistent massive pleural effusions requiring invasive mechanical ventilation and bilateral continuous thoracic drainage is rare. A thorough diagnostic workup followed by prompt initiation of immunochemotherapy can arrest pleural output, enable extubation, and be lifesaving. Clinicians should recognize that MCL rarely presents with persistent massive pleural effusions. Full article

Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis. Long-term immunomodulatory therapies, including corticosteroids, used in the management of rheumatoid arthritis are associated with a higher risk of infections. Leishmaniasis is a neglected protozoal infection that may arise in these patients. Cutaneous presentation is the most common and is characterized by a wide spectrum of clinical manifestations and courses, depending on the interplay between species involved and the host’s immune response. Here, we report the rare and intriguing case of a patient with long-standing rheumatoid arthritis, chronically treated with systemic prednisone, whose rheumatoid nodules were colonized by Leishmania major. In this context, therapeutic strategies must be tailored to species and patient factors. This report expands the differential diagnosis of rheumatoid nodule, highlighting the importance of considering opportunistic infections in exuberant presentations, particularly in immunosuppressed patients coming from or travelling in endemic regions. Intracellular pathogens may exploit the localized immunological niche represented by the rheumatoid nodule of an immunocompromised host to survive and replicate undisturbed. It also underscores the value of the clinico-pathological correlation and the importance of integrating molecular analyses to identify unexpected microorganisms that can be hidden by concomitant disease, avoiding misdiagnosis, ensuring timely treatment, and improving patients outcomes. Full article

Background: Neurotrophin receptor tyrosine kinase (NTRK) fusions are potent oncogenic mutations. Inhibitors such as larotrectinib, entrectinib and repotrectinib are used when cancer cells harbor NTRK1, NTRK2 or NTRK3 fusion. Signal disruption between nerve growth factor (NGF) and its target is thought to impact nociception. Withdrawal pain is reported with larotrectinib and entrectinib. Case presentation: Two male patients aged 37 and 41 years old and treated with, respectively, repotrectinib and larotrectinib for NTRK fusion-positive solid tumors experienced debilitating pain after abrupt cessation of their targeted therapy. Short courses of prednisone for the former and dexamethasone for the latter were initiated after failure of standard analgesia. Both patients improved within 24 h and the pain did not recur after steroids were weaned off. They had improvements in their functional status without unexpected toxicity. Conclusions and relevance: For patients experiencing TRK inhibitor withdrawal pain, especially when tapering down the inhibitor is not an available strategy, a short course of corticosteroids can provide lasting relief. These cases emphasize the importance of better understanding the mechanism underlying the relationship between NRTK, NGF and nociception. Full article