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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 8  |  Issue : 1  |  Page : 33-41

Osteoarthritis in patients with familial Mediterranean fever: genetic basis and anti-inflammatory effect of laser acupuncture


1 Department of Clinical Genetics, National Research Centre, Cairo, Egypt
2 Department of Complementary Medicine, National Research Centre, Cairo, Egypt
3 Department of Molecular Genetics and Enzymology, National Research Centre, Cairo, Egypt

Date of Submission20-Feb-2019
Date of Acceptance20-Jun-2019
Date of Web Publication25-Nov-2019

Correspondence Address:
Manal M Thomas
33rd El Bohouth Street, Dokki, Giza
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/MXE.MXE_2_19

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  Abstract 


Background
Familial Mediterranean fever (FMF) is an autosomal recessive autoimmune disease characterized by recurrent attacks of fever, peritonitis, pleuritis, arthritis, and renal amyloidosis. Arthritis could be the presenting symptom in many cases. Laser acupuncture has analgesic and anti-inflammatory effects on joint arthritis.
Aim
To highlight the genetic basis of osteoarthritis in patients with FMF and to highlight the anti-inflammatory effect of laser acupuncture on osteoarthritis of knee joint in Egyptian patients with FMF.
Patients and methods
A randomized controlled study was performed on 40 Egyptian patients with FMF. Molecular analysis of MEFV gene mutations was performed for all selected patients. Twenty patients with FMF were exposed to low-level laser acupuncture sessions (laser acupuncture group) and 20 other patients with FMF did not receive low-level laser acupuncture sessions (control group). Twelve low-level laser acupuncture sessions were implemented for the group treated with laser acupuncture three times per week for a duration of 4 weeks. All patients were checked before and after laser acupuncture sessions for pain intensity, radiography changes, and some inflammatory markers (white blood cell, eosinophils, lymphocytes, erythrocyte sedimentation rate, and C-reactive protein).
Results
M694V mutation was detected in 40% of patients. Patients with FMF with knee arthritis exposed to low-level laser acupuncture sessions showed significant improvement in pain intensity compared with the control group (P < 0.001). Statistical significance improvement of the treated knees started from the third follow-up laser session revealed by significant improvement in the radiography findings (P < 0.001). The inflammatory markers white blood cell, eosinophils, lymphocytes, erythrocyte sedimentation rate, and C-reactive protein became significantly lower (P = 0.037,P < 0.001,P < 0.001,P < 0.001, andP < 0.001, respectively).
Conclusion
M694V variant of MEFV gene is more frequent in the Egyptian patients with FMF with osteoarthritis. Low-level laser acupuncture therapy is effective in ameliorating pain of osteoarthritis in patients with FMF.

Keywords: patients with familial Mediterranean fever, low-level laser acupuncture, M694V, osteoarthritis


How to cite this article:
Thomas MM, Ahmed Kamel IE, Mohamed NH, Ramadan A, El-Bassyouni HT. Osteoarthritis in patients with familial Mediterranean fever: genetic basis and anti-inflammatory effect of laser acupuncture. Middle East J Med Genet 2019;8:33-41

How to cite this URL:
Thomas MM, Ahmed Kamel IE, Mohamed NH, Ramadan A, El-Bassyouni HT. Osteoarthritis in patients with familial Mediterranean fever: genetic basis and anti-inflammatory effect of laser acupuncture. Middle East J Med Genet [serial online] 2019 [cited 2024 Mar 29];8:33-41. Available from: http://www.mxe.eg.net/text.asp?2019/8/1/33/271568




  Introduction Top


Familial Mediterranean fever (FMF) OMIM (2017) is an autosomal recessive disorder and is associated with a missense mutation in the MEFV gene located on chromosome 16p13.3 (Akkoc and Gul, 2011). FMF mainly affects people of Mediterranean descent (Sönmez et al., 2016) with an ethnic distribution to the Turkish, Armenian, Jews, and Arab population (Sarı et al., 2014). It also affects other Mediterranean populations, such as Italians and Greeks (Ben-Chetrit and Touitou, 2009). On the contrary, it was found to affect non-Mediterranean populations, like the Japanese population (Tsuchiya-Suzuki et al., 2009).

The MEFV gene encodes for mutated protein pyrin (marenostrin), which is mainly expressed in the neutrophils, eosinophils, dendritic cells, and fibroblasts (Cantarini et al., 2012). Therefore, it has an important effect on the innate immune system cells, including neutrophils, eosinophils, and cytokine-activated monocytes. These cells play a role in the exaggerated inflammatory response through the excess production of interleukin-1 (IL-1) (Davtyan et al., 2008). Pyrin is an immune-regulatory protein made up of 781 amino acids. It interacts with caspase-1 and other inflammasome components to regulate IL-1β production, nuclear factor-κB, and leukocyte apoptosis. Inflammasomes are multiprotein complexes that play a major role in both innate and adaptive immune systems (Masters et al., 2009; De Torre-Minguela et al., 2017). The most important inflammasome is the nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 (NALP3) which is required for the synthesis of IL-1β, which is implicated in the pathogenesis of FMF and other auto-inflammatory diseases (Campbell et al., 2016).

The clinical manifestations of FMF are characterized by recurrent periods of fever, peritonitis, pleuritis, arthritis, erysipelas-like erythema, and long-term complications, mainly renal amyloidosis (Ben-Chetrit and Levy, 1998; Khalil et al., 2018).

Arthritis is the second most common symptom and the attacks are usually mono-articular typically involving large joints of the lower limbs (hips, knees, and ankles) and develop in childhood. The attack lasts for 5–7 days (Usluer and Bircan, 2007; Kucuk et al., 2014). The frequency of arthritis in FMF was reported to range between 21 and 77% in different ethnic groups (Jarjour and Dodaki, 2011). Arthritis is the presenting finding of FMF in some patients, and sometimes it remains as the only major manifestation of the disorder. Although the most common type of arthritis is recurrent, self-limited, and short lived acute inflammation of the joints, chronic forms with protracted joint effusion were occasionally reported (Majeed and Rawashdeh, 1997; Sneh et al., 1997). Risk of secondary amyloidosis was also increased in patients with FMF with arthritis (Cefle et al., 2005). M694V variation of the MEFV gene that is usually associated with the most severe clinical form was found to be more frequent in patients with arthritis (Brik et al., 1999; Tunca et al., 2005; Jarjour and Dodaki, 2011).

Clinical manifestations of arthritis in patients with FMF include joint pain, stiffness, decreased range of motion, muscle weakness, proprioceptive changes (Kaufman et al., 2001), and difficulties in daily living activities such as walking, climbing/descending stairs, and housekeeping (Bennell et al., 2007). Deformities and instabilities were also observed but joint pain is the dominant symptom which becomes accentuated when the joint is moved and relieved with rest. Persistent pain even during rest or at nocturnal rest may be a sign of advanced osteoarthritis (Michael et al., 2010). Pain and stiffness are the two primary reasons for daily life activity and mobility disability, adversely affecting the quality of life of these patients (Hunt et al., 2013). Management aims to relieve pain and improve quality of life. It also aims to increase joint mobility and function with knee stabilization, reduction of the load on the joint and most importantly, prevention of deformities and slowing the progression of the disease (Huleatt et al., 2014).

Low-level laser therapy (LLLT) has been used in arthritis and for other painful conditions without any observed adverse effects (Baltzer et al., 2017). LLLT has many clinical applications in the past few years. The effect of LLLT plays a beneficial effect by modulating the inflammatory process. LLLT has analgesic, anti-inflammatory, and regenerative effects providing pain relief in joint arthritis by improving the microcirculation (Hegedus et al., 2009). It also exerts a positive influence on ATP synthesis on the cellular level with an increase in the cellular metabolism (Hashmi et al., 2010) and cellular-molecular level on fibroblasts (Van Breugel and Bär, 1992) as well as collagen synthesis (Lam et al., 1986). LLLT inhibits the pro-inflammatory mediators such as PGE2, TNF-α, IL-1β, and COX-2 and reduces MMP activity. Furthermore, it has an analgesic effect through direct irradiation without thermal adverse effect (Carlos et al., 2014).

Acupuncture is one of the most popular treatments applied in traditional Chinese medicine and was used for relieving pain in musculoskeletal diseases (Liu et al., 2015). Manual or electrical stimulation of the acupuncture point is the most popular form of acupuncture therapy (Carbioglu et al., 2006; Mao and Kapur, 2010). Laser acupuncture using a low-intensity laser is a therapeutic method equivalent to needle acupuncture with respect to the selection of acupuncture points (Chow et al., 2012). Laser beams are characterized by being monochromatic, coherent, and collimated. Energy power, wavelength, and energy density are the three important parameters of laser acupuncture. Energy power of the LLLT was considered as the treatment dose (Glazov et al., 2016). Stimulating certain acupuncture points on the human body can release certain chemical mediators like dynorphins and endorphins which have anti-inflammatory effects and play a major role in pain relief (Mohammed et al., 2018).

The aim of the present study was to highlight the genetic basis of osteoarthritis in patients with FMF and to assess the effectiveness of laser acupuncture on the reduction of pain and improvement in the function of the knee joint. Additionally, we aimed to investigate the anti-inflammatory effect of laser acupuncture on patients with FMF by investigating the effect of laser acupuncture on the inflammatory markers [white blood cell (WBC), eosinophils, lymphocytes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)] in patients with FMF.


  Patients and Methods Top


A randomized controlled study was performed on 40 Egyptian patients with FMF. Patients were recruited from the Clinical Genetics Department in the National Research Centre, Egypt, and were referred to the Complementary Medicine Department in the center of excellence, National Research Centre, Egypt, from October 2017 to November 2017. The study was approved by the Ethical Research Committee of the National Research Centre (ethical approval number 17153) and was conducted in accordance with National Research Centre by the laws for human research. It conforms to the provisions of the Declaration of Helsinki in 2000. Parents or caregivers gave written informed consent to the study.

Patients were subjected to detailed history (including demographic data, age at the onset, detailed pedigree construction, and analysis, with special emphasis on parental consanguinity, a similar disease in the family, and treatment modalities). The diagnosis was confirmed by molecular analysis of MEFV gene mutations by PCR amplification followed by DNA sequencing analysis of exon 10 and RFLP for E148Q mutation in exon 2 (recorded hot-spots) (Zarouk et al., 2018). All selected patients experienced knee osteoarthritis at least for 3 months that did not resolve on ordinary painkillers and anti-inflammatory drugs in spite of regular doses of colchicine.

Patients were divided into two groups:

Group A (study group): it included 20 patients with FMF. Their ages ranged from 7 to 15 years, and they were exposed to laser acupuncture sessions (laser acupuncture group)

Group B (control group): it included 20 age-matched and sex-matched patients with FMF who served as controls. Their ages ranged from 6 to 14 years; they did not receive laser acupuncture sessions (control group).

Twelve laser acupuncture sessions were performed to group A patients (20 patients with FMF) three times per week for a duration of 4 weeks using a single probed cold semiconductor laser device, with power = 100 mw and wavelength = 808 nm. The maximum dose (in J) will be 5 J/cm2 which is suitable for children according to the World Association of Laser Therapy rules 2017 (World Association of Laser Therapy, 2017). We used the device on traditional Chinese acupoints for knee osteoarthritis as follows: Spleen 9 (Yanglinquan, SP9), Spleen 10 (Xuehai, SP10), Stomach 34 (Liangqui, ST34), Stomach 36 (Zusanli, ST36), and Spleen 6 (Sanyinjiao). Acupoints are points for maximum pain in the joint, which differs from one case to the other. Only extra-articular points around the knee joint were selected, to reduce the chance of infection. Different sites are illustrated in [Figure 1].
Figure 1: (a) Spleen 10: with the knee flexed, 2 cun (cun = 2.5 cm) above the superior medial border of the patella on the bulge of the medial portion of quadriceps femoris (vastus medialis). (b) Stomach 34: when the knee is flexed, on the anterior aspect of the thigh, on the line connecting the anterior superior iliac spine and the lower lateral border of the patella, 2 cun above the patella. (c) Spleen 6: 3 cun directly superior to the tip of the medial malleolus on the posterior border of the tibia. (d) Spleen 9: under the medial condyle of the tibia, in the depression posterior and inferior to the medial border of the tibia. (e) Stomach 36: 2 cun lateral to the tibial tuberosity.

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All patients were examined before and after low-level laser acupuncture sessions depending on pain intensity [no pain, mild, moderate, and severe pain according to visual analog scale (VAS)]. The linear scale is the visual representation of the range of pain that a patient believes he or she might experience. The range is represented by a line usually 100 mm in length with or without marks at each centimeter. One end represents 'no pain' whereas the other represents the worst pain the patient could imagine. Pain VAS score ranges from 0 to 100 mm: no pain (0–4 mm), mild pain (5–44 mm), moderate pain (45–74 mm), and severe pain (75–100 mm) (Hawker et al., 2011).

Investigations

It included radiography findings and inflammatory markers (WBC, eosinophils, lymphocytes, ESR, and CRP). Plain radiography was performed to verify the degree of knee osteoarthritis. Radiography findings were divided into five grades based on Kellgren and Lawrence system for classification of osteoarthritis of knee [grade 0: no radiographic features of osteoarthritis were present, grade 1: doubtful joint space narrowing (JSN) and possible osteophytic lipping, grade 2: definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph, grade 3: multiple osteophytes, definite JSN, sclerosis, and possible bony deformity, and grade 4: large osteophytes, marked JSN, severe sclerosis, and definite bony deformity] (Kellgren and Lawrence, 1957). A 5-ml blood sample was taken for a complete blood count to test for the total leukocytic (WBCs) count with differential for the eosinophils and lymphocytes in addition to ESR level and CRP, before and after the laser sessions.

Statistical analysis

The collected data were coded, tabulated, and statistically analyzed using IBM SPSS statistics (Statistical Package for Social Sciences) software (version 18.0, 2009; IBM Corp., Chicago, Illinois, USA).

Descriptive statistics were done for quantitative data as minimum and maximum of the range as well as mean ± SD for quantitative normally distributed data, median and first and third interquartile range for quantitative nonnormally distributed data, whereas for qualitative data as number and percentage.

Inferential analyses were done for quantitative variables using independent t test in cases of two independent groups with normally distributed data and paired t test in cases of two dependent groups with normally distributed data. In qualitative data, inferential analyses for independent variables were done using χ2 test for differences between proportions and Fisher's exact test for variables with small expected numbers. The level of significance taken at P value less than 0.050 is significant.


  Results Top


Demographic data for patients with FMF and controls are represented in [Table 1]. There were no statistically significant differences between the study and control groups. Positive consanguinity was found in 60% of cases in the study group and 55% of cases in the control group. Positive family history was present in 85% in both groups. Overall, 40% of patients with FMF had M694V mutation ([Table 2] and [Figure 2]).
Table 1: Demographic characteristics among the studied groups

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Table 2: Mutation results of 40 patients with familial Mediterranean fever with knee osteoarthritis

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Figure 2: Partial exon 10 sequence chromatogram of MEFV gene showing heterozygous M694V [AG] variant.

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All 20 patients with FMF in the study population completed the treatment regimen with good compliance, and the regimen was well tolerated. The knee joints were treated by 12 laser acupuncture sessions three times per week for a duration of 4 weeks. No adverse effects or any patient discomfort was reported during the treatment course. There was no significant difference between the study group and the control group regarding the basal pain (P value using Fisher's exact test 0.827), which became significantly lower in the study group than in the control group after treatment (P < 0.001). Improvement outcomes for the treated knees reached statistical significance starting from the third follow-up session ([Table 3]). Most of the improvements in pain sensation occurred between the third and fifth follow-ups. A comparison between the study and the control groups regarding the basal radiography findings showed no significant difference (P = 1). A significant improvement was noticed in the study group after treatment than in the control group (P < 0.001). Radiography findings in the study group before and after treatment showed a significant difference (P < 0.001) ([Table 4]). There was no significant difference between the study and the control groups regarding the basal levels of WBC, eosinophils, lymphocytes, ESR, and CRP (P = 0.97, 0.845, 0.657, 0.985, and 1, respectively), which became significantly lower in study group than in the control group after treatment (P = 0.037, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). The levels of WBC, eosinophils, lymphocytes, ESR, and CRP in the study group before and after treatment decreased significantly (P = 0.027, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively) ([Table 5]). The overall significant improvements in all the studied factors in the study group compared with the control group are illustrated in [Figure 2] and [Figure 3].
Table 3: Pain among the studied groups

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Table 4: Radiography findings among the studied groups

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Table 5: Laboratory findings among the studied groups

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Figure 3: Improvements among the studied groups.

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  Discussion Top


FMF is characterized by recurrent febrile attacks of peritonitis, pleuritis, and arthritis. The high-grade fever and severe pain leave the patient bedridden during the attack. Arthritis is a major and common feature of FMF. The most common arthritic attack of FMF is acute large joint mono-arthritis, most often affecting the knee and hip joints, lasting for several days (Onen, 2006). Patients with FMF with arthritis have a younger age of onset and are more prone to erysipelas-like erythema, myalgia, and vasculitis (Tunca et al., 2005).

There are no specific criteria to differentiate arthritis accompanying FMF from arthritis of other inflammatory conditions. This may lead to delayed diagnosis and the emergence of complications. Therefore, molecular analysis is an essential tool to confirm the diagnosis and give the appropriate treatment. In the present study, MEFV gene mutation was present in all patients with FMF (100%) who presented with knee osteoarthritis which supports the role of MEFV gene mutation in the inflammatory process and development of arthritis in these patients. Tunca et al. (1999) showed in their study that patients with FMF with MEFV mutations had increased levels of inflammatory markers. The relationship of MEFV gene mutation and many inflammatory diseases was also supported by studies that showed that MEFV mutation plays a role in the course and severity of such diseases like ankylosing spondylitis, rheumatoid arthritis, Behcet disease, ulcerative colitis, and juvenile rheumatoid arthritis (Booth et al., 2001; Ozen et al., 2003; Rabinovich et al., 2005; Cosan et al., 2006; Giaglis et al., 2006; Rabinovich et al., 2007; Kholoussi et al., 2018).

In our study, molecular analysis of the MEFV gene revealed the M694V variant in 40% of the patients. The other most common mutations detected in our patients were M694I (25%), M680I (15%), E148Q (10%), V726A (5%), and A744S (5%). This was consistent with other studies which reported a higher incidence of M694V variant in cases of patients with FMF with arthritis (Brik et al., 2001; Olgun et al., 2005; Tunca et al., 2005; Jarjour and Dodaki, 2011; Sarikaya et al., 2012). However, some studies did not find any genotype–phenotype correlation (Yalcinkaya et al., 2000; Ertekin et al., 2005).

Higher consanguinity in our patients (57.5%) was consistent with the autosomal recessive inheritance of FMF. Although FMF affects both males and females in a similar ratio, male affection was slightly higher (55–60%) than female affection in our patients, whereas positive family history was present in 85% of our cases. This was consistent with Sohar et al. (1967) who reported a male predominance.

In Asian traditional medicine, acupuncture is considered as one of the most effective treatment modalities, especially for diseases accompanied by severe pain (Singh, 1998). Acupuncture aims to stimulate anatomical points. This could be achieved by needles, manual pressure, electrical stimulation, magnets, low-level laser, heat, and ultrasound. The purpose of using this noninvasive technique is to achieve the best healing effect with the minimal anatomical and physiological interventions to reach the highest standards of health care and minimize rehabilitation needs (Dong, 2018). Manual or electrical stimulation of the acupuncture point is the most popular form of acupuncture therapy by stimulation of thin, solid, metallic needles inserted into the skin (Carbioglu et al., 2006). A meta-analysis done by Vickers et al. (2018) revealed that acupuncture was effective for the treatment of chronic pain, including osteoarthritis. In addition, a study done by Tu et al. (2019) showed a significant effect on using manual and electro-acupuncture for knee osteoarthritis.

Many studies showed the beneficial effect of using LLLT throughout certain wavelength application on the body surface to treat joint inflammation by relieving the pain and improving the cell function (Jamtvedt et al., 2007; Bjordal et al., 2008; de Paula Gomes et al., 2018). The advantage of using LLLT is that it is an effective, noninvasive, safe, easily applied and cost-effective technique to treat the joint inflammation (Cetiner et al., 2006).

The present study revealed significant pain relief on using low-level laser acupuncture therapy in knee osteoarthritis. All patients showed full relief to mild pain, based on the pain VAS score. This is consistent with a study done by Bjordal et al. (2007) who reported pain relief in knee osteoarthritis after 2–4 weeks of LLLT. In addition, Al Rashoud et al. (2014) studied the effect of LLLT applied to acupuncture points on the knee joint for treatment of grade 2 knee osteoarthritis and showed a significant improvement in pain on VAS and increase in serum beta-endorphin. Moreover, David (2015) reported in his study the beneficial effect of using LLLT in pain relief of knee osteoarthritis and mentioned that LLLT reduced the need for joint replacement surgery. However, Brosseau et al. (2004) reported conflicting results, and they owed this conflict to the variability in the method of application of LLLT by the wavelength, frequency, duration, dosage, and site of application points of LLLT. They recommended the use of the dosage indicated by the World Association for Laser Therapy. Another study conducted by Huang et al. (2015) showed no benefit of LLLT on knee osteoarthritis.

The protein pyrin which is encoded by the MEFV gene is an immune-regulatory protein and has a significant effect on the innate immune system cells including neutrophils and eosinophils leading to exaggerated inflammatory response (Davtyan et al., 2008). Similarly, perivascular autoimmune infiltrate of lymphocytes occurs nonspecifically as part of the inflammatory process especially joint arthritis (Barzilai et al., 2000; Pettit et al., 2001). Our study showed an elevation in the inflammatory markers WBC, eosinophils, lymphocytes, ESR, and CRP. This indicated the significant role of these elevated markers in osteoarthritis in patients with FMF. This was in agreement with previous studies that revealed elevated WBC, ESR, CRP, and other acute-phase reactants during the acute attacks in patients with FMF (Gang et al., 1999; Ben-Zvi and Livneh, 2011). Additionally, Mercan et al. (2015) revealed in their study elevated ESR and CRP levels and attributed the persistently high ESR and CRP in patients with FMF to active FMF disease, spondyloarthritis, and inflammatory bowel disease. Many studies demonstrated shifts in platelet, lymphocyte, neutrophil, and monocyte counts in autoimmune inflammatory disorders like rheumatoid arthritis, systemic lupus erythematosus, and inflammatory rheumatic disease (Uslu et al., 2015; Wu et al., 2016; Gasparyan et al., 2019).

As observed in our study, there was a significant improvement in the inflammatory markers after the laser treatment. This indicates the effect of LLLT in reducing the inflammatory process in patients with FMF. Furthermore, a study by Erer et al. (2016) used the inflammatory markers ESR, CRP, and serum amyloid A to monitor the disease activity.


  Conclusion Top


In conclusion, M694V variant of the MEFV gene is more common in the Egyptian patients with FMF with osteoarthritis. In addition, low-level laser acupuncture offers therapeutic benefits for the treatment of knee osteoarthritis in patients with FMF, through the reduction of painful swollen joints. These therapeutic effects may also be through reducing inflammation in patients with FMF after laser acupuncture. We suggest mandatory molecular analysis for all patients with FMF with monitoring disease activity, applying laser acupuncture to the affected joints, and follow-up by the inflammatory markers.[79]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Akkoc N, Gul A (2011). Familial Mediterranean fever and seronegative arthritis. Curr Rheumatol Rep13 :388–394.  Back to cited text no. 1
    
2.
Al Rashoud AS, Abboud RJ, Wang W, Wigderowitz C (2014). Efficacy of low-level laser therapy applied at acupuncture points in knee osteoarthritis: a randomised double-blind comparative trial. Physiotherapy100 :242–248.  Back to cited text no. 2
    
3.
Baltzer AWA, Stosch D, Seidel F, Ostapczuk MS (2017). Low level laser therapy: a narrative literature review on the efficacy in the treatment of rheumatic orthopaedic conditions. Z Rheumatol76 :806–812.  Back to cited text no. 3
    
4.
Barzilai A, Langevitz P, Goldberg I, Kopolovic J, Livneh A, Pras M, Trau H (2000). Erysipelas-like erythema of familial Mediterranean fever: clinicopathologic correlation. J Am Acad Dermatol42 (5 Part 1) :791–795.  Back to cited text no. 4
    
5.
Ben-Chetrit E, Levy M (1998). Familial Mediterranean fever. Lancet351 :659–664.  Back to cited text no. 5
    
6.
Ben-Chetrit E, Touitou I (2009). Familial mediterranean fever in the world. Arthritis Rheum61 :1447.  Back to cited text no. 6
    
7.
Ben-Zvi I, Livneh A (2011). Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatol7 :105–112.  Back to cited text no. 7
    
8.
Bennell KL, Hunt MA, Wrigley TV, Hunter DJ, Hinman RS (2007). The effects of hip muscle strengthening on knee load, pain, and function in people with knee osteoarthritis: a protocol for a randomised, single-blind controlled trial. BMC Musculoskelet Disord8 :121.  Back to cited text no. 8
    
9.
Bjordal JM, Johnson MI, Lopes-Martins RA (2007). Short-term efficacy of physical interventions in osteoarthritic knee pain: a systematic review and meta-analysis of randomized placebo-controlled trials. BMC Musculoskelet Disord8 :51–64.  Back to cited text no. 9
    
10.
Bjordal JM, Lopes-Martins RA, Joensen J, Couppe C, Ljunggren AE, Stergioulas A, Johnson MI (2008). A systematic review with procedural assessments and meta-analysis of Low Level Laser Therapy in lateral elbow tendinopathy (tennis elbow). BMC Musculoskelet Disord9 :75.  Back to cited text no. 10
    
11.
Booth DR, Lachmann HJ, Gillmore JD, Booth SE, Hawkins PN (2001). Prevalence and significance of the familial Mediterranean fever gene mutation encoding pyrin Q148. QJM94 :527–531.  Back to cited text no. 11
    
12.
Brik R, Shinawi M, Kepten I, Berant M, Gershoni-Baruch R (1999). Familial Mediterranean fever: clinical and genetic characterization in a mixed pediatric population of Jewish and Arab patients. Pediatrics103 :e70.  Back to cited text no. 12
    
13.
Brik R, Shinawi M, Kasinetz L, Gershoni-Baruch R (2001). The musculoskeletal manifestations of familial Mediterranean fever in children genetically diagnosed with the disease. Arthritis Rheum44 :1416–1419.  Back to cited text no. 13
    
14.
Brosseau L, Welch V, Wells G, DeBie R, Gam A, Harman K, et al. (2004). Low-level laser therapy (Classes I, II, and III) for treating osteoarthritis. Cochrane Database Syst Rev3 :CD002046.  Back to cited text no. 14
    
15.
Campbell L, Raheem I, Malemud CJ, Askari AD (2016). The relationship between NALP3 and autoinflammatory syndromes. Int J Mol Sci17 :725.  Back to cited text no. 15
    
16.
Cantarini L, Rigante D, Brizi MG, Lucherini OM, Sebastiani GD, Vitale A, et al. (2012). Clinical and biochemical landmarks in systemic autoinflammatory diseases. Ann Med44 :664–673.  Back to cited text no. 16
    
17.
Carbioglu MT, Ergene N, Tan U (2006). The treatment of obesity by acupuncture. Int J Neurosci116 :165–175.  Back to cited text no. 17
    
18.
Carlos FP, de Paula Alves da Silva M, de Lemos Vasconcelos Silva Melo E, Costa MS, Zamuner SR (2014). Protective effect of low- level laser therapy (LLLT) on acute zymosan-induced arthritis. Lasers Med Sci29 :757–763.  Back to cited text no. 18
    
19.
Cefle A, Kamali S, Sayarlioglu M, Inanc M, Ocal L, Aral O, et al. (2005). A comparison of clinical findings of familial Mediterranean fever patients with and without amyloidosis. Rheumatol Int25 :442–446.  Back to cited text no. 19
    
20.
Cetiner S, Kahraman SA, Yücetaş S (2006). Evaluation of low-level laser therapy in the treatment of temporomandibular disorders. Photomed Laser Surg24 :637–641.  Back to cited text no. 20
    
21.
Chow R, Yan W, Armati P(2012). Electrophysiological effects of single point transcutaneous 650 and 808nm laser irradiation of rat sciatic nerve: a study of relevance for low-level laser therapy and laser acupuncture. Photomed Laser Surg30 :530–535.  Back to cited text no. 21
    
22.
Cosan F, Tozkir JD, Ustek D, Ocal L, Aral O, Gul A (2006). Association of familial Mediterranean fever-related MEFV gene M694V mutation with ankylosing spondylitis. Arthritis Rheum54 :S465–S466.  Back to cited text no. 22
    
23.
David IP (2015). Does addition of low-level laser therapy (LLLT) in conservative care of knee arthritis successfully postpone the need for joint replacement? Lasers Med Sci30 :2335–2339.  Back to cited text no. 23
    
24.
Davtyan TK, Hakobyan GS, Avetisyan SA, Harutyunyan VA (2008). Engaging anti-inflammatory mechanisms and triggering inflammatory effector apoptosis during familial Mediterranean fever attack. Inflamm Res57 :65–74.  Back to cited text no. 24
    
25.
De Paula Gomes CAF, Leal-Junior ECP, Dibai-Filho AV, de Oliveira AR, Bley AS, Biasotto-Gonzalez DA, de Tarso Camillo de Carvalho P (2018). Incorporation of photo biomodulation therapy into a therapeutic exercise program for knee osteoarthritis: A placebo-controlled, randomized, clinical trial. Lasers Surg Med50 :819–828.  Back to cited text no. 25
    
26.
De Torre-Minguela C, Mesa del Castillo P, Pelegrín P(2017). The NLRP3 and pyrin inflammasomes: implications in the pathophysiology of autoinflammatory diseases. Front Immunol8 :43.  Back to cited text no. 26
    
27.
Dong FH (2018). Precise application of traditional Chinese medicine in minimally-invasive techniques. Zhongguo Gu Shang31 :493–496.  Back to cited text no. 27
    
28.
Erer B, Demirkaya E, Ozen S, Kallinich T (2016). What is the best acute phase reactant for familial Mediterranean fever follow-up and its role in the prediction of complications? A systematic review. Rheumatol Int36 :483–487.  Back to cited text no. 28
    
29.
Ertekin V, Selimoglu MA, Pirim I (2005). Familial Mediterranean fever in a childhood population in eastern Turkey. Pediatr Int47 :640–644.  Back to cited text no. 29
    
30.
Glazov G, Yelland M, Emery J (2016). Low-level laser therapy for chronic non-specific low back pain: a meta-analysis of randomized controlled trials. Acupunct Med34 :328–334.  Back to cited text no. 30
    
31.
Gang N, Drenth JP, Langevitz P, Zemer D, Brezniak N, Pras M, et al. (1999). Activation of the cytokine network in familial Mediterranean fever. J Rheumatol26 :890–897.  Back to cited text no. 31
    
32.
Gasparyan AY, Ayvazyan L, Mukanova U, Yessirkepov M, Kitas GD (2019). The platelet-to-lymphocyte ratio as an inflammatory marker in rheumatic diseases. Ann Lab Med39 :345–357.  Back to cited text no. 32
    
33.
Giaglis S, Mimidis K, Papadopoulos V, Thomopoulos K, Sidiropoulos P, Rafail S, et al. (2006). Increased frequency of mutations in the gene responsible for familial Mediterranean fever (MEFV) in a cohort of patients with ulcerative colitis: evidence for a potential disease-modifying effect? Dig Dis Sci51 :687–692.  Back to cited text no. 33
    
34.
Hashmi JT, Huang YY, Osmani BZ, Sharma SK, Naeser MA, Hamblin MR (2010). Role of low-level laser therapy in neuro-rehabilitation. Am Acad Phys Med Rehab2 (12 Suppl 2) :S292–S305.  Back to cited text no. 34
    
35.
Hawker GA, Mian S, Kendzerska T, French M (2011). Measures of adult pain. Arthritis Care Res63 :S240–S252.  Back to cited text no. 35
    
36.
Hegedus B, Viharos L, Gervain M, Galfi M (2009). The effect of low-level laser in knee arthritis: a double-blind randomized placebo-controlled trial. Photomed Laser Surg27 :577–584.  Back to cited text no. 36
    
37.
Huang Z, Chen J, Ma J, Shen B, Pei F, Kraus VB (2015). Effectiveness of low-level laser therapy in patients with knee osteoarthritis: a systematic review and meta-analysis. Osteoarthr Cartil23 :1437–1444.  Back to cited text no. 37
    
38.
Huleatt JB, Campbell KJ, Laprade RF (2014). Nonoperative treatment approach to knee osteoarthritis in the master athlete. Sports Health6 :56–63.  Back to cited text no. 38
    
39.
Hunt MA, Keefe FJ, Bryant C, Metcalf BR, Ahamed Y, Nicholas MK, Bennell KL (2013). A physiotherapist-delivered, combined exercise and pain coping skills training intervention for individuals with knee osteoarthritis: a pilot study. Knee20 :106–112.  Back to cited text no. 39
    
40.
Jamtvedt G, Dahm KT, Christie A, Moe RH, Haavardsholm E, Holm I, Hagen KB (2007). Physical therapy interventions for patients with osteoarthritis of the knee: an overview of systematic reviews. Phys Ther88 :123–136.  Back to cited text no. 40
    
41.
Jarjour RA, Dodaki R (2011). Arthritis patterns in familial Mediterranean fever patients and association with M694V mutation. Mol Biol Rep38 :2033–2036.  Back to cited text no. 41
    
42.
Kaufman KR, Hughes C, Morrey BF, Morrey M, An KN (2001). Gait characteristic of patients with knee osteoarthritis. J Biomech34 :907–915.  Back to cited text no. 42
    
43.
Kellgren JH, Lawrence JS (1957). Radiological assessment of osteo-arthrosis. Ann Rheum Dis16 :494–502.  Back to cited text no. 43
    
44.
Khalil WK, Zarouk W, Nour Eldeen G, Ramadan A, Fayez A, Esmaiel N, et al. (2018). Apoptosis, reactive oxygen species and DNA damage in familial Mediterranean fever patients. Gene Rep14 :76–80.  Back to cited text no. 44
    
45.
Kholoussi S, Kholoussi N, Zaki ME, El-Bassyouni H, Elnady H, Morcos B, Abo-Shanab A (2018). Immunological evaluation in patients with Mediterranean fever. Maced J Med Sci2 :310–313.  Back to cited text no. 45
    
46.
Kucuk A, Gezer IA, Ucar R, Karahan AY (2014). Familial Mediterranean fever. Acta Med (Hradec Kralove)57 :97–104.  Back to cited text no. 46
    
47.
Lam TS, Abergel RP, Meeker CA, Castel JC, Dwyer RM, Uitto J (1986). Laser stimulation of collagen synthesis in human skin fibroblasts cultures. Lasers Life Sci1 :61–77.  Back to cited text no. 47
    
48.
Liu YT, Chiu CW, Chang CF, Lee TC, Chen CY, Chang SC, et al. (2015). Efficacy and safety of acupuncture for acute low back pain in emergency department: a pilot cohort study. Evid Based Complement Alternat Med2015 :179731.  Back to cited text no. 48
    
49.
Majeed HA, Rawashdeh M (1997). The clinical patterns of arthritis in children with familial Mediterranean fever. QJM90 :37–43.  Back to cited text no. 49
    
50.
Mao JJ, Kapur R (2010). Acupuncture in primary care. Prim Care37 :105–117.  Back to cited text no. 50
    
51.
Masters SL, Simon A, Aksentijevich I, Kastner DL (2009). Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol27 :621–668.  Back to cited text no. 51
    
52.
Mercan R, Bitik B, Eren R, Dumludag B, Turan A, Kucuk H, et al. (2015). Underlying causes of persistently elevated acute phase reactants in patiens with familial Mediterranean fever. Pediat Rheumatol13 :P139.  Back to cited text no. 52
    
53.
Michael JWP, Schlüter-Brust U, Eysel P(2010). The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. Dtsch Arztebl Int107 :152–162.  Back to cited text no. 53
    
54.
Mohammed N, Allam H, Elghoroury E, Zikri EN, Helmy GA, Elgendy A (2018). Evaluation of serum beta-endorphin and substance P in knee osteoarthritis patients treated by laser acupuncture. J Complement Integr Med15 :pii.  Back to cited text no. 54
    
55.
Olgun A, Akman S, Kurt I, Tuzun A, Kutluay T (2005). MEFV mutations in familial Mediterranean fever: association of M694V homozygosity with arthritis. Rheumatol Int25 :255–259.  Back to cited text no. 55
    
56.
OMIM (2017). Online mendelian inheritance in man. Available from: http://omim.org/entry/249100. [Last accessed on 20 Nov 2017].  Back to cited text no. 56
    
57.
Onen F (2006). Familial Mediterranean fever. Rheumatol Int26 :489–496.  Back to cited text no. 57
    
58.
Ozen S, Bakkaloglu A, Yilmaz E, Duzova A, Balci B, Topaloglu R, Besbas N (2003). Mutations in the gene for familial Mediterranean fever: do they predispose to inflammation? J Rheumatol30 :2014–2018.  Back to cited text no. 58
    
59.
Pettit AR, Ahern MJ, Zehntner S, Smith MD, Thomas R (2001). Comparison of differentiated dendritic cell infiltration of autoimmune and osteoarthritis synovial tissue. Arthritis Rheum44 :105–110.  Back to cited text no. 59
    
60.
Rabinovich E, Livneh A, Langevitz P, Brezniak N, Shinar E, Pras M, Shinar Y (2005). Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene. Ann Rheum Dis64 :1009–1014.  Back to cited text no. 60
    
61.
Rabinovich E, Shinar Y, Leiba M, Ehrenfeld M, Langevitz P, Livneh A (2007). Common FMF alleles may predispose to development of Behcet's disease with increased risk for venous thrombosis. Scand J Rheumatol36 :48–52.  Back to cited text no. 61
    
62.
Sarı İ, Birlik M, Kasifoǧlu T (2014). Familial Mediterranean fever: an updated review. Eur J Rheumatol1 :21–33.  Back to cited text no. 62
    
63.
Sarikaya S, Özdolap S, Maraşli E (2012). Spondylitis and arthritis in familial Mediterranean fever. Arch Rheumatol27 :241–247.  Back to cited text no. 63
    
64.
Singh G (1998). Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med105 :31–38.  Back to cited text no. 64
    
65.
Sneh E, Pras M, Michaeli D, Shanin N, Gafni J (1997). Protracted arthritis in familial Mediterranean fever. Rheumatol Rehabil16 :102–106.  Back to cited text no. 65
    
66.
Sohar E, Gafni J, Pras M, Heller H (1967). Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med43 :227–253.  Back to cited text no. 66
    
67.
Sönmez HE, Batu ED, Özen S (2016). Familial Mediterranean fever: current perspectives. J Inflamm Res9 :13–20.  Back to cited text no. 67
    
68.
Tsuchiya-Suzuki A, Yazaki M, Nakamura A, Yamazaki K, Agematsu K, Matsuda M, Ikeda S (2009). Clinical and genetic features of familial Mediterranean fever in Japan. J Rheumatol36 :1671–1676.  Back to cited text no. 68
    
69.
Tu JF, Yang JW, Lin LL, Wang TQ, Du YZ, Liu ZS, et al. (2019). Efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for knee osteoarthritis: study protocol for a randomised controlled trial. Trials20 :79.  Back to cited text no. 69
    
70.
Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, et al. (2005). Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore)84 :1–11.  Back to cited text no. 70
    
71.
Tunca M, Kirkali G, Soyturk M, Akar S, Pepys MB, Hawkins PN (1999). Acute phase response and evolution of familial Mediterranean fever. Lancet353 :1415.  Back to cited text no. 71
    
72.
Uslu AU, Küçük A, Şahin A, Ugan Y, Yılmaz R, Güngör T, et al. (2015). Two new inflammatory markers associated with Disease Activity Score-28 in patients with rheumatoid arthritis: neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. Int J Rheum Dis18 :731–735.  Back to cited text no. 72
    
73.
Usluer H, Bircan Z (2007). Protracted familial Mediterranean fever arthritis presenting as septic arthritis. Rheumatol Int27 :1083–1085.  Back to cited text no. 73
    
74.
Van Breugel HHFI, Bär PRD (1992). Power density and exposure time of He-Ne laser irradiation are more important than total energy dose in photo-biomodulation of human fibroblasts in vitro. Lasers Surg Med12 :528–537.  Back to cited text no. 74
    
75.
Vickers AJ, Vertosick EA, Lewith G, MacPherson H, Foster NE, Sherman KJ, et al., Acupuncture Trialists' Collaboration (2018). Acupuncture for chronic pain: update of an individual patient data meta-analysis. J Pain19 :455–474.  Back to cited text no. 75
    
76.
World Association of Laser Therapy (2017). Recommended treatment doses for low level laser therapy. Available from: http://waltza.co.za/wp-content/uploads/2012/08/Dose_table_904nm_for_Low_Level_Laser_Therapy_WALT-2010.pdf. [Last accessed on 15 Aug 2018].  Back to cited text no. 76
    
77.
Wu Y, Chen Y, Yang X, Chen L, Yang Y (2016). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with disease activity in patients with systemic lupus erythematosus. Int Immunopharmacol36 :94–99.  Back to cited text no. 77
    
78.
Yalcinkaya F, Cakar N, Misirlioglu M, Tümer N, Akar N, Tekin M, et al. (2000)., Genotype–phenotype correlation in a large group of Turkish patients with familial Mediterranean fever: evidence for mutation-independent amyloidosis. Rheumatology (Oxford)39 :67–72.  Back to cited text no. 78
    
79.
Zarouk WA, El-Bassyouni H, Ramadan A, Fayez A, Esmaiel N, Foda BM, et al. (2018). Screening of the most common MEFV mutations in a large cohort of Egyptian patients with familial Mediterranean fever. Gene Reports11 :23–28.  Back to cited text no. 79
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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