Treatment Of Inflammatory Joint Diseases Research Articles

Prodrug Nanomedicine for Synovium Targeted Therapy of Inflammatory Arthritis: Insights from Animal Model and Human Synovial Joint Fluid.

Many patients cannot tolerate low-dose weekly methotrexate (MTX) therapy for inflammatory arthritis treatment due to life-threatening toxicity. Although biologics offer a target-specific therapy, it raises the risk of serious infections and even cancer due to immune system suppression. We introduce an anti-inflammatory arthritis MTX ester prodrug using a long-circulating biocompatible polymeric macromolecule: folic acid (FA) functionalized hyperbranched polyglycerol (HPG). In vitro the drug MTX is incrementally released through pH and enzymatic degradation over 2 weeks. The role of matrix metalloproteinases (MMPs) in site-specific prodrug activation was verified using synovial fluid (SF) of 26 rheumatology patients and 4 healthy controls. Elevated levels of specific MMPs-markers of joint inflammation-positively correlated with enhanced prodrug release explained by acid-catalyzed hydrolysis of esters by proteases. Intravenously administered 111In-radiolabeled prodrug confirmed by SPECT/CT imaging that it accumulated preferentially in inflamed joints while reducing off-target side-effects in a mouse model of rheumatoid arthritis (RA). Added FA as a targeting vector prolonged prodrug action; prodrug with 4x less MTX applied every 2 weeks was as effective as weekly MTX therapy. The preclinical results suggest a prodrug-based strategy for the treatment of inflammatory joint diseases, with potential for other chronic inflammatory diseases and cancer.

Therapeutic Drug Monitoring: A Tool to Optimize Treatment of Inflammatory Joint Diseases.

Therapeutic Drug Monitoring: A Tool to Optimize Treatment of Inflammatory Joint Diseases.

Assessing Immunogenicity of Biologic Drugs in Inflammatory Joint Diseases: Progress Towards Personalized Medicine

Biologic drugs have greatly improved treatment outcomes of inflammatory joint diseases, but a substantial proportion of patients either do not respond to treatment or lose response over time. Drug immunogenicity, manifested as the formation of anti-drug antibodies (ADAb), constitute a significant clinical problem. Anti-drug antibodies influence the pharmacokinetics of the drug, are associated with reduced clinical efficacy, and an increased risk of adverse events such as infusion reactions. The prevalence of ADAb differs among drugs and diseases, and the detection of ADAb also depends on the assay format. Most data exist for the tumor necrosis factor-alpha inhibitors infliximab and adalimumab, with a frequency of ADAb that ranges from 10 to 60% across studies. Measurement of ADAb and serum drug concentrations, therapeutic drug monitoring, has been suggested as a strategy to optimize therapy with biologic drugs. Although the recent randomized clinical Norwegian Drug Monitoring (NOR-DRUM) trials show promise towards a personalized medicine prescribing approach by therapeutic drug monitoring, several challenges remain. A plethora of assay formats, with widely differing properties, is currently used for measuring ADAb. Comparing results between different assays and laboratories is difficult, which complicates the development of cut-offs necessary for guidelines and the implementation of ADAb measurements in clinical practice. With the possible exception of infliximab, limited data on clinical relevance and cost effectiveness exist to support therapeutic drug monitoring as a routine clinical strategy to monitor biologic drugs in inflammatory joint diseases. The aim of this review is to provide an overview of the characteristics and prevalence of ADAb, predisposing factors to ADAb formation, commonly used assessment methods, clinical consequences of ADAb, and the potential implications of ADAb assessments for everyday treatment of inflammatory joint diseases.

Preclinical studies of automated radiolabeled microcarriers for radiosynovectomy of inflammatory joint disease

The broad implementation of therapeutic loaded nano- and microcarriers has led to significant progress in the treatment of inflammatory joint diseases, especially in the case of radiological synovectomy using β-emitting radioisotope labeled carriers. However, the lack of automated procedures for radiolabeling of these carriers seriously limits their further translation into clinical practice. Here, we develop the automated process of microcarriers radiolabeling for radiosynovectomy of inflammatory joint disease (synovitis in an arthritis rat model). The fabricated polymeric microparticles (MPs) possess high biocompatibility in vitro and in vivo, can be effectively loaded with 188Re therapeutic radionuclide (∼ 97,98%), and exhibit good radiochemical stability (up to 95%). In vivo biodistribution demonstrates the accumulation of intra-articular injected 188Re-MPs in the knee joint (> 96%ID/g for 7 d) without radiation exposure to other healthy organs. It has been shown that the applied radiosynovectomy with 188Re-MPs can significantly reduce knee joint swelling (knee joint with synovitis ∼ 1.8 ± 0.1 cm versus treated knee joint ∼ 1.1 ± 0.1 cm) and leads to the improvement of inflammation in synovium and cartilage recovery, decreasing the levels of inflammatory factors (TNF-α, IL-6, and IL-1b). Although there are very limited clinical trials on radiosynovectomy of inflammatory joint disease, this study is a step towards implementation of the developed automated labeling procedure for the real application of radiosynovectomy with 188Re in clinics.

The EANM guideline for radiosynoviorthesis

PurposeRadiosynoviorthesis (RSO) using the intraarticular application of beta-particle emitting radiocolloids has for decades been used for the local treatment of inflammatory joint diseases. The injected radiopharmaceuticals are phagocytized by the superficial macrophages of the synovial membrane, resulting in sclerosis and fibrosis of the formerly inflamed tissue, finally leading to reduced joint effusion and alleviation of joint pain.MethodsThe European Association of Nuclear Medicine (EANM) has written and approved these guidelines in tight collaboration with an international team of clinical experts, including rheumatologists. Besides clinical and procedural aspects, different national legislative issues, dosimetric considerations, possible complications, and side effects are addressed.ConclusionThese guidelines will assist nuclear medicine physicians in performing radiosynoviorthesis. Since there are differences regarding the radiopharmaceuticals approved for RSO and the official indications between several European countries, this guideline can only give a framework that must be adopted individually.

Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints

There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralateral joints as controls. Blood and synovial fluid were analysed for the tacrolimus concentration and biomarkers for inflammation and cartilage metabolism. After an initial burst release, sustained intra-articular tacrolimus concentrations (>20 ng/mL) were observed during the 42 days follow-up. Whole-blood tacrolimus levels were below the detectable level (<0.5 ng/mL). A transient inflammatory reaction was observed for all substances, evidenced by increases of the synovial fluid white blood cell count and total protein. Prostaglandin and glycosaminoglycan release were increased in joints injected with unloaded monospheres, which was mitigated by tacrolimus. Both tacrolimus-loaded monospheres and HA transiently increased the concentration of collagen II cleavage products (C2C). A histologic evaluation of the joints at the endpoint showed no pathological changes in any of the conditions. Together, these results indicate the good biocompatibility of intra-articular applied tacrolimus-loaded monospheres combined with prolonged local drug release while minimising the risk of systemic side effects. Further evaluation in a clinical setting is needed to determine if tacrolimus-loaded monospheres can be beneficial in the treatment of inflammatory joint diseases in humans and animals.

Preliminary bioequivalence of an oral integrating film formulation containing meloxicam with a suspension formulation in beagle dogs.

The oral disintegrating film (ODF) has advantages over suspension and tablet. These include convenience of administration, patient compliance, and accurate dosing. We evaluated the bioequivalence between the ODF and the meloxicam suspension by using a crossover design with a 3-week washout period. Six healthy male beagle dogs were randomized to receive both formulations of meloxicam, 2mg. Plasma meloxicam concentrations were measured at the same times. From the start until maximum concentration, the initial absorption of the ODF meloxicam formulation was more rapid (2.08±1.56hr) as compared to the suspension (3.33±1.03hr). Mean elimination half-lives were 28.77±4.01 and 32.85±9.79hr for the ODF and the suspension, respectively. Bioequivalence of the ODF was confirmed, based on the relative ratios of geometric mean concentrations (and 90% confidence intervals within the range of 80%-125%) for a maximum concentration of 101.05% (88.59-115.25), for the area under the plasma concentration-time curve (AUC) to the last sampling time of 96.07% (87.06-115.25), and for AUC to infinity of 92.65% (86.76-98.94). The meloxicam ODF may be used as an alternative to suspension formulations in the treatment of inflammatory joint diseases and painful musculoskeletal disorders.

Formulation and characterization of leflunomide/diclofenac sodium microemulsion base-gel for the transdermal treatment of inflammatory joint diseases

PurposeThis work aimed to investigate the release of poorly water-soluble drugs from microemulsion gel formulations using leflunomide and diclofenac combination as model drugs. MethodsCombination treatment, immunomodulatory (leflunomide), and NSAIDs (diclofenac sodium) were developed and tested for active rheumatoid arthritis. Various surfactants and cosurfactants have been tested for their ability to emulsify the selected oil process. Pseudo ternary diagrams have been developed to describe the field of the microemulsion. The microemulsion was prepared using isopropyl myristate as oil phase, tween 80 as a surfactant, and 1-pentanol as co-surfactant were assessed for droplet size, poly dispersibility index, zeta potential. ResultsThe average droplet size and zeta potential values for the selected formulation were 31.54 ± 5.37 nm and −7.14 ± 2.91, respectively. Optimized microemulsion systems were formulated into gel form to enhance the viscosity, carbopol was used to form a microemulsion gel evaluated for pH, spreadability, viscosity, drug content, differential scanning calorimetry, Fourier transforms infrared spectra analysis, and in vitro drug release using dialysis bag. For selected formulations, in vitro release has been studied and the F2C formula showed appropriate cumulative drug release (77.36% for leflunomide and 89.90% for diclofenac sodium) after 24 h. A 28-day anti-arthritic evaluation (body weight, paw edema, hematological parameters, and histopathology) on arthritic rat model showed significant relief of arthritis. ConclusionsTransdermal formulation containing leflunomide and diclofenac is introduced as a gel-based on microemulsion has shown promising results and can be considered a suitable formula for the ME gel capable of achieving sustained release.

Anti-inflammatory activity of a combined gel based on plant components in a model of adjuvant arthritis in rats

Topicality. According to WHO, more than 4 % of the population globe suffer from a variety of joint and spine disorders. In Ukraine, more than 34,500 patients with primary joint diseases are registered annually. Diseases of the musculoskeletal system have a chronic course that requires long-term treatment and puts increased demands on the effectiveness and safety of anti-inflammatory drugs. Therefore, the above justifies the feasibility and relevance of the search for new highly effective and safe domestic drugs.Aim. To make an experimental study of the pharmacological activity of a combined gel for the treatment of inflammatory joint disease if chronic inflammation – adjuvant arthritis in rats.Materials and methods. The subjects of the study were model samples of a combined gel with active pharmaceutical ingredients - white willow bark, common sage leaves dried extract and methyl salicylate. The anti-inflammatory properties of the new gel were studied using a model of adjuvant arthritis in rats (sensitization to the base of the tail by PAF at 0.1 ml/animal, and the introduction on the seventh day of a resolving dose by PAF 0.1 ml/animal under aponeurosis of the right hind limb subplantarly). Diclofenac sodium gel, 5 %, was used as the comparison drug. The test specimens were applied to the affected paw surface daily at a dose of 0.2 ml/animal. Indicators: volume of edema of animal paws (3, 7, 10, 14 and 21 days of experiment); leukocyte and FAN content in the blood and alkaline and acid phosphatase activity and serum CIK content (21 days).Results and discussion. According to the results of studies, against the background of chronic inflammation, the combined gel shows an efficiency comparing to the diclofenac sodium gel, 5 %, conceding to it only in its anti-exudative effect. However, a positive feature of the new gel, in contrast to the drug of comparison, is the ability to maintain the cellular level of non-specific animal immunity, which is significantly impaired under the condition of this pathology.Conclusions. The obtained experimental data substantiate the prospect of further pharmacological studies of the developed combination gel based on the active ingredients of white willow bark, sage medicinal leaves dried extract and methyl salicylate.

Hallazgos ultrasonográficos a nivel de articulaciones de manos y pies en sujetos voluntarios asintomáticos

IntroductionUltrasound (US) abnormalities have often been described in the joints of asymptomatic subjects, which may lead to uncertainty in the evaluation and treatment of inflammatory joint disease. Despite this, the available evidence is scarce, with few participants, and in the vast majority with transducers less than 18Mhz. In Colombia there are currently no published studies about this topic. ObjectivesTo describe the ultrasound findings in hand and foot joints in asymptomatic volunteers, their association with sociodemographic characteristics, and intra- and interobserver concordance of the measurements. Materials and methodsDescriptive and analytical study within 182 asymptomatic volunteers. Two physicians with musculoskeletal ultrasound experience evaluated the dorsal aspect of 5460 articular recesses using the semi-quantitative scale of Szkudlarek using a 18MHz linear transducer. ResultsThe median age of the participants was 42 years, including 60.4% women. A total of 232 abnormal findings were identified in 87% of the volunteers, with 68.1% corresponding to joint effusion, 29.3% synovial hypertrophy, 2.1% erosions, and 0.4% positive power Doppler. The feet evaluation showed more findings than the hands (70.7 vs. 29.3%). The joints in which most abnormalities were identified were the first metatarsophalangeal joint (52%), third metatarsophalangeal joint (15%), and radiocarpal joint (9.5%). A positive association was found between joint effusion and synovial hypertrophy with age, exclusive manual activity, and occupation for more than ten years. The intra-observer concordance was moderate (Kappa=.4591) and the inter-observer was low (Kappa=.2155). ConclusionsThe absence of power Doppler signal, the absence of abnormalities in distal radioulnar, the absence of synovitis accompanied by erosion, and a greater predominance of mild alterations in the hand joints, added to the absence of findings in the fifth metatarsal joint, can be potential specific findings of asymptomatic subjects and might be confirmed in future studies.

Ultrasound findings in hand and foot joints of asymptomatic volunteers

IntroductionUltrasound (US) abnormalities have often been described in the joints of asymptomatic subjects, which may lead to uncertainty in the evaluation and treatment of inflammatory joint disease. Despite this, the available evidence is scarce, with few participants, and in the vast majority with transducers less than 18 Mhz. In Colombia there are currently no published studies about this topic. ObjectivesTo describe the ultrasound findings in hand and foot joints in asymptomatic volunteers, their association with sociodemographic characteristics, and intra- and interobserver concordance of the measurements. Materials and methodsDescriptive and analytical study within 182 asymptomatic volunteers. Two physicians with musculoskeletal ultrasound experience evaluated the dorsal aspect of 5460 articular recesses using the semi-quantitative scale of Szkudlarek using an 18 MHz linear transducer. ResultsThe median age of the participants was 42 years, including 60.4% women. A total of 232 abnormal findings were identified in 87% of the volunteers, with 68.1% corresponding to joint effusion, 29.3% synovial hypertrophy, 2.1% erosions, and 0.4% positive power Doppler. The feet evaluation showed more findings than the hands (70.7 vs. 29.3%). The joints in which most abnormalities were identified were the first metatarsophalangeal joint (52%), third metatarsophalangeal joint (15%), and radiocarpal joint (9.5%). A positive association was found between joint effusion and synovial hypertrophy with age, exclusive manual activity, and occupation for more than ten years. The intra-observer concordance was moderate (Kappa = .4591) and the inter-observer was low (Kappa = .2155). ConclusionsThe absence of power Doppler signal, the absence of abnormalities in distal radioulnar, the absence of synovitis accompanied by erosion, and a greater predominance of mild alterations in the hand joints, added to the absence of findings in the fifth metatarsal joint, can be potential specific findings of asymptomatic subjects and might be confirmed in future studies.

A prospective observational study on the long-term results of 90Yttrium citrate radiosynoviorthesis of synovitis in osteoarthritis of the knee joint.

Radiosynoviorthesis (RSO) is used for the treatment of inflammatory joint diseases. However, there are no long-term results published comparing it to conservative therapy. Therefore, the aim of this prospective observational study was to evaluate response rates after radionuclide therapy in patients suffering from knee osteoarthritis over a time period of 10years. Radionuclide therapy with intra-articular administration of colloidal 90Yttrium citrate was performed in osteoarthritic patients [Kellgren-Lawrence grades I/II (n = 69) and Kellgren-Lawrence grade III (n = 72)]. In patients with early-stage disease, an excellent/good response with respect to pain, joint mobility, and function was observed in 82.5% for 1year and in 73.7% for 8years after therapy. Responses declined to 50% at 10years post treatment. In grade III patients, an excellent/good response was observed in 45.9%; a decline to 41.2% was observed in the first 8years. In this group, the number of patients available for follow-up after 9 and 10years dropped significantly from 51 patients after 8years to only 30 patients after 9years, and to nine patients after 10years. As a result, these response rates were not appraisable. Long-term results of radiosynoviorthesis in knee osteoarthritis are excellent/good in many patients. The response rate depends on Kellgren-Lawrence stages, and early-stage radionuclide therapy for osteoarthritis is suggested.

Joint damage in hiv positive patients

Nowadays, HIV infection remains one of the major threats to global public health. The clinical signs of HIV infection are extremely diverse and associated with many, including rheumatic diseases. This review examines the issue of osteoarticular disorders in HIV positive patients. The article presents a detailed clinical description of individual nosological forms (HIVassociated arthritis, reactive arthritis, psoriatic arthritis, etc.) and considers the issues of differential diagnosis of these diseases. Modern approaches to the treatment of inflammatory joint diseases in HIV infection, including genetic engineering biological preparations are analysed.

Inhibitory effects of sodium pentosan polysulfate on formation and function of osteoclasts derived from canine bone marrow

BackgroundSodium pentosan polysulfate (NaPPS) was testified as a chondroprotective drug in with a detailed rationale of the disease-modifying activity. This study was undertaken to determine whether anti-osteoarthritis drug, NaPPS inhibited osteoclasts (OC) differentiation and function. Canine bone marrow mononuclear cells (n = 6) were differentiated to OC by maintaining with receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for up to 7 days with the treatment of NaPPS at concentration of 0, 0.2, 1 and 5 μg/mL. Differentiation and function of OC were accessed using tartrate-resistant acid phosphate (TRAP) staining and bone resorption assay, while monitoring actin ring formation. Invasion and colocalization patterns of fluorescence-labeled NaPPS with transcribed gene in OC were monitored. Gene expression of OC for cathepsin K (CTK), matrix metallopeptidase-9 (MMP-9), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, activator protein-1(AP-1) and carbonic anhydrase II was examined using real-time PCR.ResultsSignificant inhibition of OC differentiation was evident at NaPPS concentration of 1 and 5 μg/mL (p < 0.05). In the presence of 0.2 to 5 μg/mL NaPPS, bone resorption was attenuated (p < 0.05), while 1 and 5 μg/mL NaPPS achieved significant reduction of actin ring formation. Intriguingly, fluorescence-labeled NaPPS invaded in to cytoplasm and nucleus while colocalizing with actively transcribed gene. Gene expression of CTK, MMP-9 and NFATc1 were significantly inhibited at 1 and 5 μg/mL (p < 0.05) of NaPPS whereas inhibition of c-Fos and AP-1 was identified only at concentration of 5 μg/mL (p < 0.05).ConclusionsTaken together, all the results suggest that NaPPS is a novel inhibitor of RANKL and M-CSF-induced CTK, MMP-9, NFATc1, c-Fos, AP-1 upregulation, OC differentiation and bone resorption which might be a beneficial for treatment of inflammatory joint diseases and other bone diseases associated with excessive bone resorption.

Degradation, Intra-Articular Biocompatibility, Drug Release, and Bioactivity of Tacrolimus-Loaded Poly(d-l-lactide-PEG)-b-poly(l-lactide) Multiblock Copolymer-Based Monospheres

The aim of this study was to develop a formulation with a sustained intra-articular release of the anti-inflammatory drug tacrolimus. Drug release kinetics from the prepared tacrolimus loaded monodisperse biodegradable microspheres based on poly(d-l-lactide-PEG)-b-poly(l-lactide) multiblock copolymers were tunable by changing polymer composition, particularly hydrophobic-hydrophilic block ratio. The monospheres were 30 μm and released the drug, depending on the formulation, in 7 to >42 days. The formulation exhibiting sustained release for 1 month was selected for further in vivo evaluation. Rat knees were injected with three different doses of tacrolimus (10 wt %) loaded monospheres (2.5, 5.0, and 10 mg), contralateral control knees with saline. Micro-CT and histology showed no negative changes on cartilage, indicating good biocompatibility. Minor osteophyte formation was seen in a dose dependent fashion, suggesting local drug release and therapeutic action thereof. To investigate in vivo drug release, tacrolimus monospheres were injected into horse joints, after which multiple blood and synovial fluid samples were taken. Sustained intra-articular release was seen during the entire four-week follow-up, with negligible systemic drug concentrations (<1 ng/mL), confirming the feasibility of local intra-articular drug delivery without provoking systemic effects. Intra-articular injection of unloaded monospheres led to a transient inflammatory reaction, measured by total synovial leucocyte count (72 h). This reaction was significantly lower in joints injected with tacrolimus loaded monospheres, showing not only the successful local tacrolimus delivery but also local anti-inflammatory action. This local anti-inflammatory potential without systemic side-effects can be beneficial in the treatment of inflammatory joint diseases, among which is osteoarthritis.

Diagnosis and Treatment of Inflammatory Joint Disease.

Arthritis damages the cartilage within joints, resulting in degenerative changes, including loss of function and joint instability. Ankylosing spondylitis (AS) is a chronic inflammatory condition affecting the spine and bone-to-tendon attachment area within the sacroiliac joint leading to back pain and progressive spinal stiffness. In the final stages, AS causes hyperkyphosis-a condition closely tied to the human leukocyte antigen-B27 gene. Rheumatoid arthritis is a chronic, systemic autoimmune disease characterized by the simultaneous inflammation of the synovium of multiple joints, leading to joint damage (e.g., destruction, deformation and disability). In the past, nonsteroidal anti-inflammatory drugs or conventional disease-modifying antirheumatic drug (DMARDs) have been used for the treatment of these autoimmune diseases, but biologic DMARDs have recently been introduced with excellent results. Gout is a chronic inflammatory disease that causes an alteration of joints resulting in severe pain. Specifically, gout is associated with an accumulation of uric acid within the body resulting from dysregulated purine metabolism, causing recurrent paroxysmal inflammation in the joints. Allopurinol and febuxostat are the primary treatment options for individuals with gout. It is necessary to have an accurate understanding of the pathogenesis, pathological ecology and treatment of AS, rheumatoid arthritis, and gouty arthritis, which are the representative diseases that may cause inflammatory arthritis.

JUVENILE ARTHRITIS: CLINICAL MANIFESTATIONS AND DIFFERENTIAL DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

The diagnosis and treatment of inflammatory joint diseases is the pressing problem of pediatric rheumatology and orthopedics. Juvenile arthritis is the most frequent chronic inflammatory disease of the musculoskeletal system in children and adolescents. Still juvenile arthritis is often misdiagnosed. The article provides current knowledge on juvenile arthritis, its clinical manifestations, as well as diagnostic and treatment strategies, and differential diagnosis.

THU0132 A Prospective Observational Study on Long-Term Results of 90Yttrium Radiosynoviorthesis of Chronic Knee Synovitis in Rheumatoid Arthritis and Osteoarthritis Patients

BackgroundInflammatory joint diseases are very common and are causing severe disability and reduced activity. Since more than 60 years radiosynoviorthesis is used for treatment of inflammatory joint diseases. In the...

AB0366 Pleiotropic Effects of Statins in the Treatment of Inflammatory Joint Diseases

BackgroundA lot of clinical studies have shown the beneficial pleiotropic effects of statins: both associated with reduction of cardiovascular risk, and response to the locomotory system such as their effects...

Manifestation of Crohn's disease in a young woman during the course of treatment for severe form of chronic plaque psoriasis with etanercept

With the growing number of patients with immune-modulated diseases treated with tumor necrosis factor (TNF) alpha inhibitors, we are more frequently encountering the occurrence of so-called paradoxical drug reactions. These are basically situations where during the course of the treatment of one disease, the manifestation of another with similar etiopathogenesis occurs, although under normal conditions this newly developed disease responds well to treatment with TNF alpha inhibitors and is indicated for this treatment. Skin reactions are most frequently recorded in the form of induced psoriasis and psoriasiform exanthems. A less common paradoxical reaction is the induction of Crohn's disease, which is most often described in association with the treatment of inflammatory joint diseases with etanercept. We present a case of induction of Crohn's disease during therapy with etanercept, where the primary disease being treated was psoriasis. In the literature, similar cases have only been described sporadically.