Psoriasis beyond the skin: an expert group consensus on the management of psoriatic arthritis and common co-morbidities in patients with moderate-to-severe psoriasis

BACKGROUND Psoriatic arthritis (PsA) and co-morbidities of psoriasis represent a significant clinical and economic burden for patients with moderate-to-severe psoriasis. Often these co-morbidities may go unrecognized or undertreated. While published data are available on the incidence and impact of some of them, practical guidance for dermatologists on detection and management of these co-morbidities is lacking. OBJECTIVE To prepare expert recommendations to improve the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis. METHODS A systematic literature review was conducted on some common co-morbidities of psoriasis-cardiovascular (CV) diseases (including obesity, hypertension, hyperglycaemia and dyslipidaemia), psychological co-morbidities (including depression, alcohol abuse and smoking) and PsA-to establish the incidence and impact of each. Data gaps were identified and a Delphi survey was carried out to obtain consensus on the detection and management of each co-morbidity. The expert panel members for the Delphi survey comprised 10 dermatologists with substantial clinical expertise in managing moderate-to-severe psoriasis patients, as well as a cardiologist and a psychologist (see appendix) with an interest in dermatology. Agreement was defined using a Likert scale of 1-7. Consensus regarding agreement for each statement was defined as ≥75% of respondents scoring either 1 (strongly agree) or 2 (agree). RESULTS The expert panel members addressed several topics including screening, intervention, monitoring frequency, and the effects of anti-psoriatic treatment on each co-morbidity. Consensus was achieved on 12 statements out of 22 (3 relating to PsA, 4 relating to psychological factors, 5 relating to CV factors). The panel members felt that dermatologists have an important role in screening their psoriasis patients for PsA and in assessing them for psychological and CV co-morbidities. In most cases, however, patients should be referred for specialist management if other co-morbidities are detected. CONCLUSION This article provides useful and practical guidance for the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis.

Pelvic tilt is minimally changed by total hip arthroplasty

BACKGROUND While surgical navigation offers the opportunity to accurately place an acetabular component, questions remain as to the best goal for acetabular component positioning in individual patients. Overall functional orientation of the pelvis after surgery is one of the most important variables for the surgeon to consider when determining the proper goal for acetabular component orientation. QUESTIONS/PURPOSES We measured the variation in pelvic tilt in 30 patients before THA and the effect of THA on pelvic tilt in the same patients more than a year after THA. METHODS Each patient had a CT study for CT-based surgical navigation and standing and supine radiographs before and after surgery. Pelvic tilt was calculated for each of the radiographs using a novel and validated two-dimensional/three-dimensional matching technique. RESULTS Mean supine pelvic tilt changed less than 2°, from 4.4° ± 6.4° (range, -7.7° to 20.8°) before THA to 6.3° ± 6.6° (range, -5.7° to 19.6°) after THA. Mean standing pelvic tilt changed less than 1°, from 1.5° ± 7.2° (range, -13.1° to 12.8°) before THA to 2.0° ± 8.3° (range, -12.3° to 16.8°) after THA. Preoperative pelvic tilt correlated with postoperative tilt in both the supine (r(2) = 0.75) and standing (r(2) = 0.87) positions. CONCLUSIONS In this population, pelvic tilt had a small and predictable change after surgery. However, intersubject variability of pelvic tilt was high, suggesting preoperative pelvic tilt should be considered when determining desired acetabular component positioning on a patient-specific basis.

Juvenile onset central nervous system folate deficiency and rheumatoid arthritis.

Isolated cerebral folate deficiency was detected in a 13-year-old girl with cognitive and motor difficulties and juvenile rheumatoid arthritis. Her serum contains autoantibodies that block membrane-bound folate receptors that are on the choroid plexus and diminish the uptake of folate into the spinal fluid. Whereas her serum folate exceeded 21 ng/mL, her spinal fluid contained 3.2 ng/mL of 5-methyltetrahydrofolate as a consequence of the autoantibodies diminishing the uptake of this folate.

The course of radiographic loosening, pain and functional outcome around the first revision of a total hip arthroplasty

Background: The published data on pain and physical function before and after revision of total hip arthroplasty (THA) is scarce. The study reports the course and interrelationships of radiographic loosening, pain and physical function 5 year before and after a first revision THA. Methods: The study was based on the IDES-THA database. All patients with their first THA revision for aseptic loosening and a documented index surgery on the same side and at least one pre-revision and one post-revision follow-up were selected. Only patients with an intact contralateral hip joint (Charnley class-A) were included. Follow-ups within ±5.5 years around the revision time point were analyzed. Annual prevalences of radiographic component loosening and the non-desired outcomes (moderate/severe/intolerable pain, walking <30 minutes, hip flexion range <90°) were calculated. Results: Signs of radiographic component loosening started to increase about 4 years before revision surgery. Two years later, a sharp increase of painful hips from 15% to 80% in the revision year was observed. In the year after revision surgery, this rate dropped back to below 10%. Walking capacity started to noticeably deteriorate 3 years before revision and in the revision year about 65% of patients could not walk longer than 30 minutes. As opposed to pain, walking capacity did not recover to pre-revision levels and the best outcome was only reached two years post-revision. Hip flexion range had the slowest and least extent of deterioration (≈45% flexed <70° in the revision year) but with the best outcomes at only three years after revision surgery it took the longest to recover. Conclusion: Prevalence of radiological loosening signs and/or pain intensity follow an almost parallel course around the first revision of a THA for aseptic component loosening. This process begins about 4 years (radiographic loosening) before the actual revision surgery and intensifies about 2 years later (pain). It also involves walking capacity and hip range of motion. While pain levels go back to levels similar to those after primary surgery, range of motion and even more walking capacity remain moderately compromised.

The relationship between rheumatoid arthritis and reproductive function

There is growing support for the theory that an interaction between the immune and reproductive/endocrine systems underlies the pathogenesis of autoimmune rheumatic diseases. Most of the recent evidence derives from studies of sex hormones and pregnancy in women with systemic lupus. Other than an ameliorative effect of pregnancy, little is known about reproductive factors in relation to rheumatoid arthritis. To elucidate the relationship, a population-based retrospective study was undertaken. Included were 378 female residents of Olmsted County, Minnesota diagnosed with rheumatoid arthritis between 1950 and 1982 (cases) and 325 arthritis-free, married female controls matched to the 324 married cases on birth-year, age at first marriage, and duration of Olmsted County residency. Information of reproductive factors was extracted from the medical records system maintained by the Mayo Clinic.^ Cases had lower fertility rates compared with the female population of Minnesota (rate ratio = 0.86, 95% confidence interval (CI)= 0.80-0.92). Fertility was significantly reduced even prior to the onset of rheumatoid factor positive arthritis. Restricting the comparison to married Olmsted County residents did not alter the results. Further adjustments for time not at risk of conception using survival analysis and proportional hazards modeling only intensified the fertility reduction in the married cases compared with controls. Nulligravidity was more common among cases than controls (odds ratio = 3.16, CI = 1.61-6.20). Independent of fertility, pregnancy had a protective effect against rheumatoid arthritis (odds ratio = 0.31, CI = 0.11-0.89), which was dramatically reversed in the 12 months postpartum (odds ratio = 4.67, CI = 1.50-14.47). Cases were younger at menopause than controls (p $<$ 0.01).^ Small but statistically insignificant associations were observed between rheumatoid arthritis and the following factors: increased frequency of complaints to a physician of infertility; increased frequency of spontaneous abortion, premature birth, and congenital malformations following arthritis onset; and increased prevalence of menopause at arthritis onset. Cases did not differ from controls on age at menarche, duration of pregnancy, or birth weight.^ The findings provide further support for the involvement of the reproductive/endocrine systems in the pathogenesis of autoimmune rheumatic disease. The search for biological mechanisms should be intensified. ^

cDNA cloning and expression of a novel cell surface-expressed \b heparan sulfate/heparin \b interacting \b protein (HIP) from human cell lines and functional studies of a synthetic HIP peptide

Heparan sulfate proteoglycans and their corresponding binding sites have been suggested to play an important role during the initial attachment of blastocysts to uterine epithelium and human trophoblastic cell lines to uterine epithelial cell lines. Previous studies on RL95 cells, a human uterine epithelial cell line, characterized a single class of cell surface heparin/heparan sulfate (HP/HS)-binding sites. Three major HP/HS-binding peptide fragments were isolated from RL95 cell surfaces by tryptic digestion and partial amino-terminal amino acid sequence from each peptide fragment was obtained. In the current study, using the approaches of reverse transcription-polymerase chain reaction and cDNA library screening, a novel cell surface $\rm\underline{H}$P/HS $\rm\underline{i}$nteracting $\rm\underline{p}$rotein (HIP) has been isolated from RL95 cells. The full-length cDNA of HIP encodes a protein of 259 amino acids with a calculated molecular weight of 17,754 Da and pI of 11.75. Transfection of HIP cDNA into NIH-3T3 cells demonstrated cell surface expression and a size similar to that of HIP expressed by human cells. Predicted amino acid sequence indicates that HIP lacks a membrane spanning region and has no consensus sites for glycosylation. Northern blot analysis detected a single transcript of 1.3 kb in both total RNA and poly(A$\sp+$) RNA. Examination of human cell lines and normal tissues using both Northern blot and Western blot analysis revealed that HIP is differentially expressed in a variety of human cell lines and normal tissues, but absent in some cell lines examined. HIP has about 80% homology, at the level of both mRNA and protein, to a rodent protein, designated as ribosomal protein L29. Thus, members of the L29 family may be displayed on cell surfaces where they participate in HP/HS binding events. Studies on a synthetic peptide derived from HIP demonstrate that HIP peptide binds HS/HP with high selectivity and has high affinity (Kd = 10 nM) for a subset of polysaccharides found in commercial HIP preparations. Moreover, HIP peptide also binds certain forms of cell surface, but not secreted or intracellular. HS expressed by RL95 and JAR cells. This peptide supports the attachment of several human trophoblastic cell lines and a variety of mammalian adherent cell lines in a HS-dependent fashion. Furthermore, studies on the subset of HP specifically recognized by HIP peptide indicate that this high-affinity HP (HA-HP) has a larger median MW and a greater negative charge density than bulk HP. The minimum size of oligosaccharide required to bind to HIP peptide with high affinity is a septa- or octasaccharide. HA-HP also quantitatively binds to antithrombin-III (AT-III) with high affinity, indicating that HIP peptide and AT-III may recognize the same or similar oligosaccharide structure(s). Furthermore, HIP peptide antagonizes HP action and promotes blood coagulation in both factor Xa- and thrombin-dependent assays. Finally, HA-HP recognized by HP peptide is highly enriched with anticoagulant activity relative to bulk HP. Collectively, these results demonstrate that HIP may play a role in the HP/HS-involved cell-cell and cell-matrix interactions and recognizes a motif in HP similar or identical to that recognized by AT-III and therefore, may modulate blood coagulation. ^

Exercise for osteoarthritis of the hip.

BACKGROUND Current international treatment guidelines recommending therapeutic exercise for people with symptomatic hip osteoarthritis (OA) report are based on limited evidence. OBJECTIVES To determine whether land-based therapeutic exercise is beneficial for people with hip OA in terms of reduced joint pain and improved physical function and quality of life. SEARCH METHODS We searched five databases from inception up to February 2013. SELECTION CRITERIA All randomised controlled trials (RCTs) recruiting people with hip OA and comparing some form of land-based therapeutic exercise (as opposed to exercises conducted in water) with a non-exercise group. DATA COLLECTION AND ANALYSIS Four review authors independently selected studies for inclusion. We resolved disagreements through consensus. Two review authors independently extracted data, assessed risk of bias and the quality of the body of evidence for each outcome using the GRADE approach. We conducted analyses on continuous outcomes (pain, physical function and quality of life) and dichotomous outcomes (proportion of study withdrawals). MAIN RESULTS We considered that seven of the 10 included RCTs had a low risk of bias. However, the results may be vulnerable to performance and detection bias as none of the RCTs were able to blind participants to treatment allocation and, while most RCTs reported blinded outcome assessment, pain, physical function and quality of life were participant self reported. One of the 10 RCTs was only reported as a conference abstract and did not provide sufficient data for the evaluation of bias risk.High-quality evidence from nine trials (549 participants) indicated that exercise reduced pain (standardised mean difference (SMD) -0.38, 95% confidence interval (CI) -0.55 to -0.20) and improved physical function (SMD -0.38, 95% CI -0.54 to -0.05) immediately after treatment. Pain and physical function were estimated to be 29 points on a 0- to 100-point scale (0 was no pain or loss of physical function) in the control group; exercise reduced pain by an equivalent of 8 points (95% CI 4 to 11 points; number needed to treat for an additional beneficial outcome (NNTB) 6) and improved physical function by an equivalent of 7 points (95% CI 1 to 12 points; NNTB 6). Only three small studies (183 participants) evaluated quality of life, with overall low quality evidence, with no benefit of exercise demonstrated (SMD -0.07, 95% CI -0.23 to 0.36). Quality of life was estimated to be 50 points on a norm-based mean (standard deviation (SD)) score of 50 (10) in the general population in the control group; exercise improved quality of life by 0 points. Moderate-quality evidence from seven trials (715 participants) indicated an increased likelihood of withdrawal from the exercise allocation (event rate 6%) compared with the control group (event rate 3%), but this difference was not significant (risk difference 1%; 95% CI -1% to 4%). Of the five studies reporting adverse events, each study reported only one or two events and all were related to increased pain attributed to the exercise programme.The reduction in pain was sustained at least three to six months after ceasing monitored treatment (five RCTs, 391 participants): pain (SMD -0.38, 95% CI -0.58 to -0.18). Pain was estimated to be 29 points on a 0- to 100-point scale (0 was no pain) in the control group, the improvement in pain translated to a sustained reduction in pain intensity of 8 points (95% CI 4 to 12 points) compared with the control group (0 to 100 scale). The improvement in physical function was also sustained (five RCTs, 367 participants): physical function (SMD -0.37, 95% CI -0.57 to -0.16). Physical function was estimated to be 24 points on a 0- to 100-point scale (0 was no loss of physical function) in the control group, the improvement translated to a mean of 7 points (95% CI 4 to 13) compared with the control group.Only five of the 10 RCTs exclusively recruited people with symptomatic hip OA (419 participants). There was no significant difference in pain or physical function outcomes compared with five studies recruiting participants with hip or knee OA (130 participants). AUTHORS' CONCLUSIONS Pooling the results of these 10 RCTs demonstrated that land-based therapeutic exercise programmes can reduce pain and improve physical function among people with symptomatic hip OA.

Correlation of urinary nitric oxide concentrations with the development of hip dysplasia in Labrador retrievers

Urinary nitric oxide was determined in terms of the ratio of the concentrations of total urinary nitrite and nitrate:creatinine in 40 juvenile labrador retrievers, and radiographic signs of hip dysplasia and distraction indices were investigated in the same dogs in later life. The ratio was correlated significantly with the Norberg angle and with subchondral sclerosis in both hips, and with the grade of dysplasia in each hip and the dogs' overall grade of hip dysplasia. No correlations were observed between the ratio and the distraction indices or other radiographic criteria for hip dysplasia.

The biomechanics of the hip joint using new diagnostic aspects in the field of hip joint dysplasia. Constructive criticism of hip dysplasia diagnosis and present marketable breeding methods with an outlook on future perspectives and possibilities. Part I

In absence of basic canine hip biomechanics, a specific, consequent three dimensional concept to evaluate the coxofemoral joint was developed for the dog. With the help of a new method to radiologically demonstrate the hip in a physiological standing position several new clinically relevant aspects could be further investigated. For example the breed specific anatomical differences in the hip, and dynamics and the background on "iatrogenic luxations" in HD diagnostics could be shown. The caudal luxation and the growth abnormalities of the hip and their consequences on the whole leg (antetorsion syndrome) as a consequence of inadequate breeding could be demonstrated.

Diagnosis and management of developmental dysplasia of the hip from triradiate closure through young adulthood

Abstract The current treatment of painful hip dysplasia in the mature skeleton is based on acetabular reorientation. Reorientation procedures attempt to optimize the anatomic position of the hyaline cartilage of the femoral head and acetabulum in regard to mechanical loading. Because the Bernese periacetabular osteotomy is a versatile technique for acetabular reorientation, it is helpful to understand the approach and be familiar with the criteria for an optimal surgical correction. The femoral side bears stigmata of hip dysplasia that may require surgical correction. Improvement of the head-neck offset to avoid femoroacetabular impingement has become routine in many hips treated with periacetabular osteotomy. In addition, intertrochanteric osteotomies can help improve joint congruency and normalize the femoral neck orientation. Other new surgical techniques allow trimming or reducing a severely deformed head, performing a relative neck lengthening, and trimming or distalizing the greater trochanter.  An increasing number of studies have reported good long-term results after acetabular reorientation procedures, with expected joint preservation rates ranging from 80% to 90% at the 10-year follow-up and 60% to 70% at the 20-year follow-up. An ideal candidate is younger than 30 years, with no preoperative signs of osteoarthritis. Predicted joint preservation in these patients is approximately 90% at the 20-year follow-up. Recent evidence indicates that additional correction of an aspheric head may further improve results.

Surgical hip dislocation for treatment of femoroacetabular impingement: factors predicting 5-year survivorship.

BACKGROUND Patients with femoroacetabular impingement (FAI) often develop pain, impaired function, and progression of osteoarthritis (OA); this is commonly treated using surgical hip dislocation, femoral neck and acetabular rim osteoplasty, and labral reattachment. However, results with these approaches, in particular risk factors for OA progression and conversion to THA, have varied. QUESTIONS/PURPOSES We asked if patients undergoing surgical hip dislocation with labral reattachment to treat FAI experienced (1) improved hip pain and function; and (2) prevention of OA progression; we then determined (3) the survival of the hip at 5-year followup with the end points defined as the need for conversion to THA, progression of OA by at least one Tönnis grade, and/or a Merle d'Aubigné-Postel score less than 15; and calculated (4) factors predicting these end points. METHODS Between July 2001 and March 2003, we performed 146 of these procedures in 121 patients. After excluding 35 patients (37 hips) who had prior open surgery and 11 patients (12 hips) who had a diagnosis of Perthes disease, this study evaluated the 75 patients (97 hips, 66% of the procedures we performed during that time) who had a mean followup of 6 years (range, 5-7 years). We used the anterior impingement test to assess pain, the Merle d'Aubigné-Postel score to assess function, and the Tönnis grade to assess OA. Survival and predictive factors were calculated using the method of Kaplan and Meier and Cox regression, respectively. RESULTS The proportion of patients with anterior impingement decreased from 95% to 17% (p < 0.001); the Merle d'Aubigné-Postel score improved from a mean of 15 to 17 (p < 0.001). Seven hips (7%) showed progression of OA and another seven hips (7%) converted to THA Survival free from any end point (THA, progression of OA, or a Merle d'Aubigné-Postel < 15) of well-functioning joints at 5 years was 91%; and excessive acetabular rim trimming, preoperative OA, increased age at operation, and weight were predictive factors for the end points. CONCLUSIONS At 5-year followup, 91% of patients with FAI treated with surgical hip dislocation, osteoplasty, and labral reattachment showed no THA, progression of OA, or an insufficient clinical result, but excessive acetabular trimming, OA, increased age, and weight were associated with early failure. To prevent early deterioration of the joint, excessive rim trimming or trimming of borderline dysplastic hips has to be avoided.