Current Rheumatology Reviews - Volume 13, Issue 2, 2017

Parasitic infections are among the oldest and most common infections in humans. Host defense alterations caused by autoimmune diseases or immunosuppressive drugs can cause modifications of the symptoms: indolent parasites can be reactivated, asymptomatic patients may experience new symptoms, or mild or moderate symptoms can become serious and, rarely, may lead to death. In recent years, new drugs have been used in the treatment of rheumatoid arthritis (RA), causing a greater level of immunosuppression and, therefore, more concerns regarding the risk of serious parasitic diseases. Of note, experimental studies have demonstrated that the immunomodulation induced by infection with helminths can minimize the occurrence and severity of rheumatoid arthritis. Products derived from helminths (such as glycoprotein ES-62) can exert favorable effects in RA patients via their anti-inflammatory actions. Greater knowledge of these substances may serve as a basis for the development of new treatments for RA. The full impact of parasitic diseases on patients with rheumatoid arthritis remains controversial, and further studies are warrented.

Localized scleroderma (LS) is characterized by excessive collagen deposition leading to thickening of the dermis, subcutaneous tissue or both. The outcome for most patients with localized scleroderma is directly related to the type and stage of the affected tissue. The major challenge for untreated patients is not increased mortality risk, rather deformity and growth defects from skin, muscle and bone abnormalities. Treatment is individualized to type and stage of the lesion and may include pharmacologic and non-pharmacologic therapies. Among the pharmacologic modalities, methotrexate with systemic glucocorticoids is currently the mainstay of treatment. More controlled trials are needed to determine the length of treatment and the maintenance dose of this combination therapy.

Background: The identification and validation of soluble markers provide significant opportunities for managing patients with rheumatic diseases, and calprotectin may be an alternative laboratory biomarker of inflammatory rheumatoid arthritis (RA) and psoriatic arthritis (PsA) even though its levels may vary considerably. The aim of this study was to propose a calprotectin cut-off value that would be useful for distinguishing patients with inflammatory arthritis or noninflammatory arthritis (NIA) in clinical practice. Methods: A commercial enzyme-linked immunosorbent assay was used to measure serum calprotectin levels in patients with RA, ankylosing spondylitis (AS), PsA and controls with NIA. All of the patients had been treated with biological disease-modifying anti-rheumatic drugs (DMARDs) for about 12 months after previous failure on conventional DMARDs. Results: Receiver operating characteristic (ROC) analysis showed that serum calprotectin levels significantly differentiated the samples of the patients with inflammatory rheumatic disease from those of the controls. A serum calprotectin level of > 0.9 μg/mL (the optimal predictive cut-off value in the ROC analysis) had a sensitivity of 95.3%, a specificity of 82.2%, a positive likelihood ratio (LR) of 5.35 and a negative LR of 0.057. Conclusions: Our findings suggest that serum calprotectin levels are useful in clinical practice to distinguish patients with inflammatory arthritis and NIA. Further studies of a larger population are suggested.

Generalized pain with tender points in specific areas accompanied by systemic symptoms such as fatigue and stiffness is characteristic of fibromyalgia (FM) syndrome. The genesis of FM is still being investigated with conflicting data on factors including autonomic dysfunction, neurotransmitters, and hormones often in combination with external stressful events. However, recent research is starting to suggest that there is a previously underappreciated subtype of fibromyalgia called inflammatory Fibromyalgia (iFM). Recent studies have described cytokines, inflammatory markers, sleep disorders, hyperalgesia, cognitive dysfunction, serum leptin levels and other inflammatory indicators as potential markers for iFM. This article will; 1) review the inflammatory markers and abnormal levels of other laboratory indicators that can help to identify the subgroup of patients that fall into the new category of Inflammatory Fibromyalgia [1-5] and 2) review all completed trials that were focused on treating this new category of disease. Through this review it is hoped that and further understanding of the complexity of the etiology of fibromyalgia can be explored.

Fatigue impacts 80-90% of patients with systemic lupus erythematosus (SLE), and an incomplete understanding of fatigue mechanisms limits effective treatment. Disease activity indices and laboratory markers inconsistently correlate with fatigue severity in SLE populations. Identification of fatigue biomarkers has important implications for understanding pathogenesis and defining novel therapeutic targets, but a paucity of evidence exists for fatigue biomarkers in SLE. The evidence for adipokines, reduced glutathione, iron deficiency, and vitamin D as potential biomarkers for SLE-related fatigue are reviewed. To address gaps in the SLE literature, the experience of each fatigue biomarker in other diseases is examined. Finally, biomarker associations with SLE pathogenesis and disease activity are discussed, as further rationale for investigation among SLE patients.

Eosinophilic fasciitis (EF), a rare connective tissue disorder, was first reported by Lawrence Shulman in 1974. Since then over 300 cases have been reported worldwide. EF has variable clinical presentations and currently does not have internationally accepted diagnostic criteria. Dermatological features are the most ubiquitously present symptoms. It often presents with sclerodermalike skin changes. Extracutaneous presentations, such as arthritis and carpal tunnel syndrome can precede cutaneous changes. The most useful clinical features are the lack of Raynaud's phenomenon, telangiectasia and visceral involvement, differentiating it from Scleroderma. Haematological disorders, solid tumours and autoimmune disorders are frequently associated with EF. Historically, the presence of peripheral eosinophilia, elevated ESR and hypergammaglobulinemia were considered to be diagnostic of EF. It is now well recognised that neither the presence of eosinophilia in the blood nor eosinophilic infiltartion in the fascia is necessary for its diagnosis. An en bloc surgical biopsy including skin, subcutis, fascia and muscle is the gold-standard test for diagnosing EF. Magnetic resonance imaging helps to locate a suitable biopsy site and to monitor treatment response. Although its underlying aetiology is unknown, there is a growing body of evidence supporting an immunological origin. Immunosuppressive drugs are used to treat EF and the corticosteroid is the first line treatment. A significant proportion of patients can develop permanent disabilities such as joint contractures, tendon retraction and subdermal sclerosis. Occasionally it can be treatment refractory or have a relapse-remitting course. We report another case of EF with a literature review.

Ankylosing Spondylitis (AS) is a chronic inflammatory disease with gradual onset, largely affecting the axial skeleton. As leads to varying degrees of restricted spinal mobility, pain and loss of functional capacity. Rehabilitation, especially physiotherapy and exercises, are considered integral components of its management. Various rehabilitation modalities are available for the benefit of individuals with AS, but a sequenced protocol has not been reported. A scientific review was performed using the following search engines: MEDLINE (Pubmed), COCHRANE Library and Physiotherapy Evidence Database (PEDro). Studies, which had at least one of the groups receiving rehabilitation, and the major outcomes studied including pain, stiffness, mobility (spine and chest wall) and physical function (disease activity, ADL, QOL and global function) were selected. A total of 28 studies were shortlisted for the review which included a total of 1926 subjects with AS. The review of literature showed that individuals with AS had beneficial effects from exercise programmes compared to no exercise. Patient education, active involvement and motivation of individuals with AS played an important role in the overall treatment outcomes. Based on the review, a four-phase sequenced rehabilitation protocol has been laid down for the benefit of individuals with AS.

Background: Popliteal fossa, also known as the popliteal space, is located behind the knee joint. This region can develop many clinical complications in the vascular, nervous, lymphatics, adipose, as well as swelling and masses. Objective: The objective of this review article is to give a detailed understanding of the popliteal fossa and the clinical pathology that may present itself. Methods: MEDLINE® searches were conducted of literature published since 1950s for “popliteal fossa,” “diseases,” “anatomy,” “arterial,” “venous,” “nerves,” “entrapment syndrome,” “aneurysms,” “cysts,” “lymphatics,” “solid masses,” “tumors,” “inflammatory lesions,” and “swellings.” The references provide up-to-date literature for all the pathologies discussed. Results: This review articles discusses the anatomy, clinical examination, including history, physical, and imaging modalities, and various diseases that present themselves in patients. Diseases relating to the arterial and venous systems, nervous system, musculature, adipose, lymphatics, cysts and other solid masses, including neoplasms, and abscesses. The differential diagnosis and symptoms of certain conditions are addressed to isolate the root of the manifestation. Conclusion: Diseases of the popliteal fossa can use histology and electrophysiology to aid in diagnosis, as well as instrumentation. Surgical approaches are uses to treat varying pathologies as they are the best means of therapy.

Background and Objective: Experimental models suggest the use of different therapy protocols in rheumatoid arthritis (RA) as modulators on periodontal condition. This study evaluated the effects of conventional drug treatment and anti-TNF therapy in patients with RA on microbiological and periodontal condition, establishing the association of markers of periodontal infection with indexes of rheumatic activity. Materials and Methods: One hundred seventy nine individuals with RA were evaluated (62 with anti-TNF-α and 115 with only DMARDs). The periodontal evaluation included plaque and gingival indexes, bleeding on probing (BOP), clinical attachment loss (CAL), pocket depth (PD) and subgingival plaque samples for microbiological analysis. Rheumatologic evaluations included a clinical examination, rheumatoid factor (RF), antibodies against cyclic-citrullinated peptides (ACPAs), and activity markers (DAS28-ERS), high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR). Results: Anti-TNF-alpha; therapy influenced periodontal microbiota with a higher frequency of T. denticola (p=0.01). Methotrexate combined with leflunomide exhibited a higher extension of CAL (p=0.005), and anti-TNF-alpha; therapy with methotrexate was associated with a lower extension of CAL (p=0.05). The use of corticosteroids exerted a protective effect on the number of teeth (p=0.027). The type of DMARD affected P. gingivalis, T. forsythia and E. nodatum presence. Elevated ACPAs titers were associated with the presence of red complex periodontal pathogens (p=0.025). Bleeding on probing was associated with elevated CPR levels (p=0.05), and ESR was associated with a greater PD (p=0.044) and presence of red complex (p=0.030). Conclusion: Different pharmacological treatments for RA affect the clinical condition and subgingival microbiota.

Objective: To determine if there is an association between focal and systemic bone loss in patients with RA. Methods: Bone loss is a hallmark finding in rheumatoid arthritis (RA) and manifests as localized, periarticular and systemic bone loss. RA patients were selected from the Consortium of Rheumatology Researchers of North America (CORRONA) database. Multiple logistic regression models were constructed to assess the association between the presence or absence of erosions and T-scores at the lumbar spine (LS) and total hips and adjusted for age, gender, body mass index (BMI), medications and disease activity indices. Results: Data on erosions and T-scores were available in 3,898 and 5,099 subjects, respectively. Patients with erosions had a significantly lower LS T-scores (-0.9) compared to RA patients without erosions (p=0.0002). Similarly, the mean total hip T-scores were significantly lower in patients with (-1.4) compared to subjects without erosions (-1.0) (p<0.01). The odds of having no erosion increased by 21% for each 1-unit increase in LS T-score and 46% for each 1 unit increase in hip Tscore. Patients with erosions were significantly younger (p<0.01) had a lower BMI (p<0.01) and higher DAS28 scores than those without erosions. More patients with erosions were on anti-TNF therapy, disease modifying drugs and osteoporosis medications than patients without erosions (p<0.01, 0.003 and 0.0003). Conclusion: RA patients with bone erosions have significantly lower T-scores at the LS and hips compared with RA patients without erosions. These data suggest a relationship between localized and generalized bone loss in RA.

The causal link between inherited complement deficiencies and systemic lupus erythematosus (SLE) has been well established, although it remains a rare cause of the disease. We present the case of three biological sisters with hereditary heterozygous C2 deficiency, but who differ widely in their clinical and serological manifestations. Patient 1 is 25 years old and was diagnosed with SLE at the age of 12. Further testing revealed positive ANA and anti-dsDNA, antiphospholipid syndrome (APS) and decreased C2, C3 and C4 levels. Patients 2 and 3 are 21-year-old dizygotic twins. Both have positive ANA and antiphospholipid (APL) antibodies, and decreased C2 and C4 levels. We present a case of familial heterozygous C2 deficiency with different disease phenotypes. The presence of positive APL antibodies in all 3 patients is significant, as this association has been rarely described. The variable clinical and serological manifestations among our patients further reflect the complex and multifactorial nature of SLE.