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Test-retest reliability of isometric hip muscle strength measured using handheld dynamometry: a pilot study

Introduction: Hip muscle weakness has been shown to be associated with lower limb pain and (re)injury. A reliable means of assessing hip muscle strength is required to assist sports physicians, orthopaedic surgeons, and physiotherapists in assessing injury risk and applying preventative measures such as appropriately prescribed and monitored exercise intervention. This study aimed to determine the relative and absolute test-retest reliability of a testing procedure assessing the isometric strength of hip flexors, extensors, abductors, adductors, internal rotators, and external rotators using handheld dynamometry.
Methods: 10 healthy subjects with an average age of 25.5 years (± SD 6.0 years) had the isometric strength of their six hip muscle groups measured by one tester using a handheld dynamometer. Subjects were tested on two separate occasions with an average interval of 5.7 days. Intra-class correlation coefficients (ICC) and the standard error of measurement (SEM) were used as measures of relative and absolute reliability respectively.
Results: All six hip muscle groups demonstrated ‘excellent’ test-retest relative reliability (ICC 0.86–0.97). Absolute reliability ranged from 3.3–7% and 0.03–0.13 Nm/kg as a measure of unit strength.
Discussion: This protocol demonstrates excellent test-retest reliability for analysis of the isometric strength of all six hip muscle groups using a handheld dynamometer. This protocol serves as an important reference for clinical assessment of hip muscle function.

Introduction
Test-retest reliability of isometric hip muscle strength measured using handheld dynamometry: a pilot studyAdequate hip muscle strength is required to control the alignment of the lower limb and therefore limit exposure of distal structures to potentially damaging forces. [1] Deficits in hip muscle strength have demonstrated an association with pain and (re)injury in the hip, [2,3] knee, [4,5] and ankle. [6] Consistent with these observations, strengthening of hip muscles through exercise interventions has been shown to reduce lower limb pain and injury, [7,8] improve lower limb landing alignment, and minimise potentially injurious positions. [9] Given this well established link between hip muscle strength impairment, pain, and (re)injury; a reliable, clinically applicable means of measuring hip muscle function is necessary to assist clinicians in the development and monitoring of interventions aimed at minimising pain and (re)injury, and improving patient function.

In the clinical setting, strength is conventionally assessed using manual muscle testing (MMT). MMT provides only a rated score (ranging from zero to five) of strength [10] and relies on clinical judgement of strength relative to the contralateral limb and/or previous strength testing experiences. A more quantitatively accurate measure of muscle strength can be obtained using dynamometry. Dynamometry measures the force produced on a maximum voluntary contraction and in contrast to MMT it provides an objective unit measure of strength. Many laboratory dynamometry stations used previously [11,12] have poor clinical utility as they are expensive and lack easy portability. In contrast, handheld dynamometry is an inexpensive and portable means of measuring strength amenable to clinical use.
Reliability is also an important component of clinical utility. Relative and absolute reliability have been identified as two distinct measures. [13] Relative reliability assesses the level of agreement between values. [14] It provides information about the association between test-retest data but not the proximity of the values. [13] Absolute reliability measures the variability between test-retest data, with less variability representing greater reliability. [13] A number of studies have assessed the reliability of handheld dynamometry on hip muscle strength testing. [7,15-20] A small number have established reliability using a handheld device for all six hip muscle groups. [2,21,22] These studies have included strength testing positions where the tester is required to stabilise the subject or hold the non-test limb during testing, leaving only one arm available to counteract the force produced by the hip muscles. Given the magnitude of force produced by the hip muscles [18] and that reliability is affected by the tester’s ability to apply sufficient counteracting force, [23] it is important that for a reliable strength testing procedure, positions are chosen to facilitate stability for not only the subject but also the tester.

There is no single, universally accepted testing protocol for all six hip muscle groups. Previous investigations have included testing positions that have required the tester to stabilise the subject. More stable testing positions are required to account for the magnitude of force produced by the hip musculature. The purpose of this pilot study was to therefore assist in establishing the test-retest relative and absolute reliability of a strength testing protocol for hip flexion, extension, abduction, adduction, internal rotation, and external rotation using handheld dynamometry.

Methods

Subjects

Approval for this study was obtained through the University of South Australia Human Research Ethics Committee. Five healthy male and five healthy female subjects were recruited via a convenience sample through an Adelaide Physiotherapy and Sports Medicine clinic. The means and standard deviations of height (1.72m ± 0.09m), mass (71.7 ± 9.9kg), and age (25.5 ± 6.0 years) were established. Subjects were included if they had no history of pain or clicking/clunking sensations from either hip joint. Subjects were excluded if they reported pain during the strength assessment period that would limit the production of a maximum voluntary contraction. Furthermore, to limit error in the measures that may be due to strength gains from exercise training, subjects were excluded if they were participating in regular lower limb strengthening exercises. Strength was assessed by the same tester on two separate occasions with an average test-retest interval of 5.7 days (range 5–7 days). All subjects were graded as performing at a ‘sufficient’ level of physical activity measured using the Active Australia Survey. [24]

Strength Assessment

Strength of the six hip muscle groups was measured using a Nicholas handheld dynamometer (HHD) (Lafayette Instruments, Lafayette, IN, USA). Strength data was recorded in kilograms (kg) and then converted to torque values with the force in Newtons (N) (where 1kg = 9.81N) multiplied by the action length in metres (m), giving a unit of Newton-metres (Nm). The action length is the perpendicular distance from the axis of rotation to the line of force (i.e. the placement point of the dynamometer). The action length for flexion, extension, abduction, and adduction was measured as the distance from the greater trochanter of the femur to the lateral femoral epicondyle, and for rotation from the lateral femoral condyle to the base of the lateral malleolus. Each action length was recorded as the average of two measures for each measured action length based on the protocol for measuring limb length validated by Beattie and colleagues. [25] To account for the confounding effect of body size on strength, [26] data was normalised to body mass, which was measured in kilograms (kg) using the same scales (Hanson, Croissy-sur-Seine, France) for each subject.

Subjects were tested on the same height adjustable plinth. Strength was assessed using the ‘make’ test where the subject’s isometric muscle action is matched by the tester. [17] To ensure the dynamometer force plate was maintained in a perpendicular position relative to the test limb, the tester’s arm was positioned with elbows locked in extension. Pillows were used as required to achieve and maintain subject positions with the hip joint in a neutral orientation in reference to adduction, abduction, internal rotation, and external rotation for all positions (Figure 1). Participants were given instructions including a description and passive demonstration of the action required, the movements to avoid, and the instruction to “push as hard as you can”. They were asked to give one sub-maximal contraction of 50 percent effort, followed by three tests of maximal effort (consistent with previous methodologies used [15]) separated by a 5 second rest. Tests were initiated and ceased with a single beep and not the tester’s verbal commands. Given that isometric muscle strength has been shown to be influenced by motivational states, [27] this method was employed to limit the tester’s influence over the subject’s performance through varying volume or verbal inflections that can differentially affect subject effort. Therefore no encouragement was offered during tests. The strongest of the tests was recorded. If the last test produced the strongest result the subject was retested to ensure improvements in strength were not a result of habituation and the subject’s best effort or maximum had been achieved. Subjects were retested if they reported failure to achieve maximum effort, or if stabilisation of the device and/or subject during testing was inadequate. The dynamometer limited tests to five seconds, to allow enough time for the generation of maximum tension. [17] The maximum force produced within the five second test period was recorded by the dynamometer. Because several muscles within the hip contribute to more than one hip joint movement, the order of strength assessment was randomised between participants. The tester was blind to strength data from the first test session until retest data was gathered.

Subject Positioning

Hip flexion was measured in sitting, with the hip and knee flexed to 90o (Figure 1a). The plinth height was standardised for each subject as the height of two fingers between the plantar-flexed foot and the floor, hence feet were not in contact with the ground, eliminating compensation by calf muscles. For the remaining muscle groups the plinth was adjusted to be as low as possible. The HHD was positioned on the surface of the skin immediately proximal to the superior pole of the patella (as shown previously [15]). Hip extension was measured in prone with the hips in neutral (Figure 1b) and legs supported by a foam wedge. The dynamometer was placed on the surface of the skin of the posterior thigh two centimetres proximal to the femoral epicondyles. [21,28] Participants were instructed to lift their thigh from the table without bending or straightening their knees, or pushing their shin into the foam wedge. Hip abduction and adduction were measured in side lying (Figure 1c, d). The subject was instructed to lift their test limb into the air while keeping their pelvis and knees straight and not to rotate their thigh in or out. The dynamometer was placed immediately superior to the lateral (abduction) and medial (adduction) femoral epicondyles. [21] Internal rotation and external rotation were assessed in side lying with the subject instructed to rotate their thigh by lifting the ankle of their test limb into the air (Figure 1e, f). The dynamometer was placed two centimetres proximal to the lateral (internal rotation) and medial (external rotation) malleoli. [21]

Data Analysis

Histograms and values of skewness demonstrated all data to be distributed normally. Bland-Altman plots were used to determine if there was a relationship between magnitude and measurement error (heteroscedasticity) present within the data. [29] Paired t-tests were used to determine the presence of systematic bias. [29] A probability level of 5% (p < 0.05) was assumed to be significant. Relative reliability was established via intra-class correlation coefficients (model 2,1) (ICC) and were interpreted as excellent (> 0.75), fair to good (0.40 to 0.75), or poor (< 0.40) according to classifications by Shrout and Fleiss. [30] Absolute reliability was assessed using the standard error of measurement (SEM) and was calculated by the equation: [SEM = SD x √(1 – ICC)], where SD is the standard deviation of the strength data from all subjects for each muscle group. [14] The SEM was presented as a unit of strength (Nm/kg) and as a percentage of the average of test and retest means of each muscle group as per previous methods. [22] A threshold beyond which a true change in strength is said to have occurred was determined for each muscle group. This is termed the minimum detectable change (MDC) and was calculated by multiplying the SEM by the square root of 2 (to account for error associated with repeated measures) and the z-score of 1.64 to establish a 90% confidence interval. [16] This confidence interval was dictated by the sample size. All data was analysed using SPSS for Windows 17.0 (SPSS, SPSS Inc., Chicago, IL, USA).

Figure 1. Subject positioning for strength testing of (a) flexion, (b) extension, (c) abduction, (d) adduction, (e) internal rotation, (f) external rotation.
Figure 1. Subject positioning for strength testing of (a) flexion, (b) extension, (c) abduction, (d) adduction, (e) internal rotation, (f) external rotation.

Results

Paired t-tests showed no differences (p > 0.05) between repeated measures for all muscle groups. Bland-Altman plots showed no heteroscedasticity present within the data. ICC values, as a measure of relative reliability, ranged from 0.86 – 0.97 (Table 1), which is classified as ‘excellent’ reliability by Shrout and Fleiss. [30] The lower boundary of the 95% confidence interval fell below this classification for hip flexion only (Table 1). As a measure of absolute reliability, the SEM represented as a unit of strength ranged from 0.03 Nm/kg to 0.13 Nm/kg and as a percentage from 3.3% to 7% (Table 1). MDC data ranged from 0.070 Nm/kg to 0.302 Nm/kg (Table 1) and represented the minimum change required in subsequent testing to reason with 90% confidence that a true change in strength has occurred and that differences are not a result of measurement error.

Table 1. The test and retest strength (Nm/kg) means and their standard deviations. Paired t-tests showed no difference between these means (p > 0.05). Also shown are the intra-class correlation coefficients (model 2,1) (ICC) and their 95% confidence intervals, the standard error of measurements (SEM) as units of strength (Nm/kg) and as a percentage of the average of test and retest means, and the minimum detectable change (MDC) (Nm/kg).
Table 1. The test and retest strength (Nm/kg) means and their standard deviations. Paired t-tests showed no difference between these means (p > 0.05). Also shown are the intra-class correlation coefficients (model 2,1) (ICC) and their 95% confidence intervals, the standard error of measurements (SEM) as units of strength (Nm/kg) and as a percentage of the average of test and retest means, and the minimum detectable change (MDC) (Nm/kg).

Discussion

This study contributes to the establishment of a reliable isometric strength testing protocol for hip flexion, extension, abduction, adduction, internal rotation, and external rotation using handheld dynamometry. This protocol serves as an important reference for clinical assessment of hip muscle function. Both relative and absolute test-retest reliability were assessed, giving insight into both the level of agreement and variability between repeated measures. Overall, findings were consistent with analysis of the present study’s raw force data, indicating that the measurement of action length and body mass did not affect reliability. Relative reliability was examined using intra-class correlation coefficients. This method differs from previous studies, which calculated the level of agreement via Pearson’s correlation coefficient, [2,21] a measure designed to assess the relationship between two variables rather than the same variable tested twice. [31]‘Excellent’ relative reliability [30] was demonstrated for the strength testing procedure for all six hip muscle groups (Table 1). This classification is comparable with analyses of the less clinically applicable ‘gold standard’ [32] laboratory dynamometry stations [11,28] and hand-held dynamometry investigations that assessed reliability from data gathered in the same test session, [21] where reliability may be overstated because the variable of subject setup is not tested twice. The use of two test occasions may leave the present study more exposed to systematic error. However, the absence of such error is supported by paired t-tests (p > 0.05) and normally distributed data. Absolute reliability was examined using the SEM. During repeated measures, some variability will be observed even if there is no reason to suspect a change in strength parameters. Given the SEM assumes an absence of heteroscedasticity, Bland-Altman plots were necessary as ratio data, such as that of the present study, is susceptible to an increase in measurement error as the measured value increases. [29]

The adductors had the largest SEM (7%); however, their ICC value indicated good agreement (0.94). The standard deviation observed in test and retest adduction means is consistent with heterogeneity that, where present, will inflate the ICC value. [13] The level of error demonstrated here by the SEM may be explained by the sensitivity of the area of the thigh where the HHD was placed. For subjects who consequently reported discomfort a hand towel was placed under the HHD to allow a maximum voluntary contraction. Nonetheless, this level of error is still comparable with previous investigations (7.8%) assessing hip adduction in this position, but with the HHD placed at the ankle. [22]

The hip flexors demonstrated the lowest ICC (0.86). Although these findings are in contrast to previous analyses of laboratory dynamometry (0.70–0.71), [11] the lower boundary of the ICC confidence interval (0.53) in the present study must be considered in the interpretation of this value. Given that the ability to counteract the force produced by the subject affects reliability, [18] it follows that the hip flexors, which generated the greatest torque, also demonstrated the lowest ICC. Furthermore, to prevent the subject from ‘cheating’ by the use of their calf muscles (see Methods), the plinth height was raised. As a result, the tester’s ability to position their upper body to provide sufficient counteracting force may have been compromised. As abduction and extension were tested with the plinth set as low as possible, this rationale is consistent with these muscle groups producing the next highest mean torque values, but also demonstrating the highest ICC (0.97). This ICC value is inconsistent with that demonstrated for abduction previously, [22] where the side-lying position was also adopted (ICC 0.74). Here the authors used one hand to hold the dynamometer and the other to stabilise the pelvis. While this aims to maximise subject stability, it may compromise the tester’s ability to counteract the force produced. Force being a vector, it has components of magnitude and direction. Changes in orientation of the HHD relative to the line of force of the hip motion may influence force transmission to the HHD (Figure 2). Using only one arm to hold the dynamometer may be insufficient to properly counteract both the magnitude and the direction of the force produced. Given that controlling for both these components of force is influenced by the tester, the present study chose positions that maximise not only the stability of the subject, but also that of the tester. These positions sought to permit the tester to position themselves and the HHD above and in line with the line of action of the test limb and were not dependent on the tester to stabilise the subject. Internal rotation and external rotation positions were hence also dictated by this notion with both demonstrating relative and absolute reliability comparable with previous findings supporting their use as a potential alternative to the more commonly utilised sitting position. [5,15,16,21,22]

Figure 2. The effects of changes in the angle of the dynamometer force plate relative to the line of motion of the test limb on force recorded during strength testing. Here the dynamometer is no longer in line with the line of force of the hip motion, (i.e. the angle has increased from 0o). If Ѳ is equal to 30o, and a subject produces 100 Newtons (N), then 116.3 Newtons will be transmitted to the dynamometer (C = 100 Newtons/cosine 30o).
Figure 2. The effects of changes in the angle of the dynamometer force plate relative to the line of motion of the test limb on force recorded during strength testing. Here the dynamometer is no longer in line with the line of force of the hip motion, (i.e. the angle has increased from 0o). If Ѳ is equal to 30o, and a subject produces 100 Newtons (N), then 116.3 Newtons will be transmitted to the dynamometer (C = 100 Newtons/cosine 30o).

Although this study demonstrates excellent test-retest reliability, the limitations must be acknowledged. The nature of this investigation as a pilot study dictated the sample size and while the reliability established is comparable with previous studies of larger samples (e.g. Pua et al. [16]), further analysis may be needed to investigate the lower boundary of the confidence interval of the flexion ICC. Secondly, the MDC data offer clinicians guidelines as to when ‘real’ changes in strength have occurred which will assist in interpreting and monitoring data before and after intervention. However, given this study did not assess reliability between multiple testers, MDC data is based on the assumption that the clinician uses the dynamometer reliably and they therefore have sufficient strength to match those being tested, as is assumed to be the case in the present study given the findings. Finally, the action length will not have fully represented the length from the centre of the axis of rotation. However because of the deep location of the hip joint, the greater trochanter was reasoned to be a more reliable landmark to measure from.

Conclusion

The present study’s protocol demonstrates excellent test-retest reliability, hence supporting its use as a measure of hip muscle function. Application of this measure can assist clinicians such as sports physicians, orthopaedic surgeons, and physiotherapists with clinical examination of injuries associated with hip muscle function, exercise prescription, and the monitoring of strength changes associated with intervention. Furthermore, this protocol offers a reliable means of measuring strength deficits and therefore injury risk as well as a reliable means of measuring performance at a strength-based level in sports where hip muscle function is important.

Future Directions

This study has established a reliable strength testing protocol for the assessment of strength of all six hip muscle groups. In contrast to previous methods, the protocol offers positions, which aim to maximise subject stability to allow the tester to counteract both the magnitude and direction of force produced by the hip musculature.

Acknowledgements

The authors wish to acknowledge Saunders Sports and Spinal for the use of their facilities for subject testing.

Conflicts of Interest

There are no conflicts of interest to declare.

References

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Articles Case Reports

Adult Onset Still’s Disease – a diagnostic dilemma

Introduction

ASOD is characterised by fever, an evanescent skin rash, polyarthralgia, hepatosplenomegaly, leucocytosis, liver enzyme elevation and a high serum ferritin level. [1,2,3] It is a difficult diagnosis to make, as there is no pathognomonic test for the disease and it is a great mimicker of other conditions, such as autoimmune disorders and haematological malignancies.

Despite being a separate clinical entity to JIA and rheumatoid arthritis, there is evidence to suggest that AOSD as well as JIA are triggered by viral infections. [2,3,4] The following case demonstrates a young man who was diagnosed with AOSD following an infection with Epstein Barr Virus. This is impetus for a discussion of the interplay between AOSD and a viral aetiology, and the innate and adaptive immune responses in guiding effective therapy.

Case Presentation

In 2012, a previously healthy 20 year old male presented with a sore throat, malaise, tender cervical lymphadenopathy and fever, consistent with infectious mononucleosis. He was transferred to a secondary referral hospital where paired EBV serology was positive for an active infection despite a negative monospot test. The patient’s travel history and past medical history were unremarkable apart from regular alcohol binge drinking.

After being discharged, he began to experience intermittent fevers and night sweats. In addition to this, he had ongoing malaise and was forced to stop work as a mechanic. Weight loss of 10kg occurred during a two month period, along with a persisting microcytic anaemia, with a haemoglobin level of approximately 8.0 g/dL.

His polyarticular pain was distributed mainly to his ankles, knees, shoulders and wrists, and associated with morning stiffness and visible swelling. The pain was partially responsive to regular ibuprofen. He also complained of intermittent pleuritic chest pain. Over a course of two months, his weight stabilised and night sweats improved, but his anaemia and polyarthralgias persisted.

Approximately two months after his initial diagnosis of infectious mononucleosis, the patient represented to hospital with severe polyarthralgias and was unable to walk. During this admission, he was afebrile but had some mild tender cervical lymphadenopathy with no hepatosplenomegaly. A pleural rub was auscultated. He had a salmon-coloured non-blanching rash on the medial aspect of both legs that felt like a ‘sunburn’; this was biopsied. Although the diagnosis of ASOD had previously been considered, the patient was investigated for other causes for these symptoms. The results of these investigations are presented in Table 1. His investigations included a bone marrow and trephine biopsy, which revealed a markedly hypercellular bone marrow. The skin biopsy of the rash on his legs showed a leucocytoclastic vasculitis with perivascular neutrophilic invasion, but negative staining for complement. This finding is non-specific to the condition and can occur due to drug reaction, immune-complex deposition or be idiopathic. [5] As test results did not indicate another likely cause for his symptoms, the patient was commenced on treatment for ASOD and was referred to a rheumatologist.

Case Discussion

This case illustrates the unique clinical and laboratory picture of AOSD, with its intermitting and remitting fevers, polyarthralgias, myalgias, lymphadenopathy, transient macular rash and pleuritis. It is likely that the patient had a degree of pleuritis, as suggested clinically with a pleural rub and on CT imaging. Serositis manifesting as pleuritis, pleural effusions or pericarditis can be encountered in ASOD, but is rare. [3,6] The rash is fleeting and may only last for hours or days, and skin biopsies generally reveal a non-specific perivascular inflammation. [1] Our patient’s thrombocytosis and markedly elevated serum ferritin are reactive changes. The serum ferritin level has been suggested as a predictive marker for AOSD as it is invariably elevated and often higher than levels found in other autoimmune or inflammatory diseases, with a five-fold increase in serum ferritin being 41% specific and 80% sensitive as a diagnostic test. [9] The markedly high ferritin level in AOSD has been attributed to hyper-production by the reticuloendothelial system or hepatocyte damage, and is unrelated to iron metabolism. [8] The patient’s blood results illustrated a microcytic anaemia, although the iron studies point towards an inflammatory reaction.

The leukocyte count appears to correlate well with the activity of illness. The underlying mechanism of this is probably bone marrow granulocyte hyperplasia, as demonstrated on bone marrow biopsy in our patient. It is not uncommon to see marked reductions in red cell counts, weight loss and hypoalbuminaemia in active disease. [8]

In our patient, causes of fever of unknown origin with or without rash were considered, such as endocarditis, haematological malignancies and systemic vasculitides. The single cytopaenia, normal LDH and bone marrow biopsy excludes leukaemia, lymphoma and myelodysplasia. It is unlikely he had a protracted course of EBV due to the nature of his symptoms and degree of anaemia, in addition to the negative EBV IgM serology. Given the recent heavy rainfall, migrating polyarthritic conditions such as Ross River and Barmah Forest viruses were considered in the differentials.

The diagnosis of ASOD is made after taking into account the patient’s medical history and risk factors for other infectious agents, environment and relevant infectious diseases epidemiology. Although being a diagnosis of exclusion, there are two commonly used clinical criteria in practice, that being Yamaguchi (Table 2), which has been shown to be most sensitive (93.5%) followed by Cush’s (80.6% sensitivity). [7,8]

In regards to the aetiology of AOSD, there have been numerous case reports of AOSD following viral infection, [4,10] with one citing an older female patient diagnosed with AOSD after EBV infection. [2] Other implicated viruses include rubella, mumps, cytomegalovirus, parainfluenza, human herpes virus 6, echovirus, parvovirus B19, and bacterial infections like mycoplasma pneumoniae, chlamydia pneumonia, yersinia enterocolitica and borrelia. [2,8] Although relevant to our patient, the link between infections and AOSD has not been robustly established from an aetiological perspective, [10] and probably only forms part of the multifaceted pathogenesis, that being a dysregulated immune system combined with susceptible HLA loci. However, no consistent associations between AOSD and particular HLA loci have been elucidated, although HLA-B17, HLA-B18, HLA-B35 and HLA-DR2 have been implicated. [6]

It does appear that pathogenesis of the condition overlies autonomous activity of both innate and adaptive immune systems. Patients with AOSD often show hypercomplementaemia, and serum levels of IL-1β, IL-6, IL-18, TNFα, IFN Ɣ and macrophage-colony stimulating factor (M-CSF) have been found to be considerably higher than compared with controls. [6,7,11] These cytokines also appear to share a role in increasing the production of ferritin. [1,12] IL-18 is predominantly secreted by macrophages and has been implicated in hepatotoxicity [13] and joint disease, [7] and may be the cause of liver enzyme derangement characteristic of AOSD. Serum IL-18 levels also appear to correlate significantly with serum ferritin levels. [8] Furthermore, IL-18 may be seen as the part of the bridge between activation of the innate and adaptive immune systems in AOSD, as it facilitates the Th1 response and induces other cytokines like IL-1 β, TNFα and IFNƔ. [6] Pro-inflammatory cytokines such as IL-6, TNFα and IFN Ɣ also increase the expression of Toll-like receptors (TLR), and high circulating levels of cytokines leads to a higher sensitivity of TLR to anti-microbial or viral peptides, thus creating a self-perpetuating cycle of inflammatory response and augmentation. [14]

On the adaptive immunity side of the pathogenesis, the role of T cells in pathogenesis has been well documented. [11,14] Dysregulated production of a particular subset of T helper cells, called Th17 cells, that secrete IL-17 have been implicated in the development of autoimmune diseases. [15] Significantly higher levels of Th17 cells and serum IL-17 levels were found in both AOSD and SLE patients, and there was a parallel decrease with clinical remission. [10] IL-17 stimulates monocytes to produce IL-6 and IL-1β, which are also principle cytokines involved in the differentiation of CD4+ T cells into Th17 cells. [6] These therefore augment and maintain the inflammatory cascade. [16]

Non-steroidal anti-inflammatory drugs (NSAIDS) had previously been the first line medication for ASOD, despite only being effective monotherapy in less than 15% of patients. [10] The benefits of corticosteroids are higher when patients have more pronounced joint disease, with a response rate of two thirds of the patient population. [10]

Highlighting the implicated cytokines, namely IL-1β, IL-6 and TNFα, [17,18] will guide the use of targeted therapies such as the disease modifying anti-rheumatic drugs (DMARDS). There have been favourable results with corticosteroids, and more than two thirds of patients require corticosteroids after NSAIDs are attempted as symptom relief. [6] The use of DMARDS are indicated where the condition is refractory to corticosteroids without signs of remission, or in combination as corticosteroid-sparing agents. This includes methotrexate, which has indirect actions on TNFα and IL-6. Although there is a lack of robust evidence regarding TNF in the pathogenesis of ASOD compared to rheumatoid arthritis, the use of etanercept and infliximab have shown significant improvement in disease in several case series. [10] Of particular note, there is increasing evidence to suggest that anakinra, an IL-1 receptor antagonist, is well tolerated, and several case series have yielded positive results in ameliorating the disease at a haematological, biochemical and cytokine level. An excess of IL-1β inducing factor has been demonstrated in JIA, a condition that also shares similar pathogenesis to that of AOSD. [6,19]

The clinical course of AOSD is heterogeneous, with patients falling into one of three clinical patterns. The first group which affects about 60% of patients [8] is a monocyclic systemic group with only one episode of systemic manifestations, with complete remission within one year of the onset of symptoms. The second group is polycyclic systemic, whom experience more than one episode which is followed by partial or total remission. The third group is a chronic articular group, with persistent polyarthritis lasting longer than 6 months. [6] In the chronic group, the average duration of disease is 10 years, the symptoms appear to be less permanent than other rheumatological diseases and the disease shows less propensity to interfere with social functioning or time off from work despite disability and the need for long-term medication. [20]

Patient outcome

The patient improved satisfactorily with regular ibuprofen and prednisolone 20 mg daily and was discharged after day 7 with a tapering steroid dose.

He was able to resume work, but continued to experience mild intermittent polyarthralgias with no other significant systemic symptoms. Six months post-admission, deterioration in arthritic symptoms prompted the addition of methotrexate.

Key points

  • Adult Onset Stills Disease is a rare systemic inflammatory disorder that mainly affects people aged 16-35 years old.
  • It is a difficult diagnosis to make, and one that must be questioned continually, as it is a mimicker of other disorders, including other causes of fever of unknown origin, infectious diseases and malignancy.
  • It is characterised by both clinical and laboratory manifestations like fever, evanescent rash, polyarthritis and polymyalgias, microcytic anaemia, leucocytosis, thrombocytosis and marked hyperferritinaemia.
  • Treatment is based on clinical course and is similar to that of rheumatoid arthritis. A more targeted biological disease modifying therapy should be chosen with consideration of likely pathogenic pro-inflammatory cytokines.

Consent declaration

Consent from the patient was gained for the writing and distribution of this article for education purposes.

Acknowledgements

Thank you to Dr. Hedley Griffiths, Consultant Rheumatologist.

Conflict of interest

None declared.

Correspondence

S Ooi: soo@deakin.edu.au

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