History Of Familial Mediterranean Fever Research Articles

Malignant Peritoneal Mesothelioma Complicating Familial Mediterranean Fever on 18 F-FDG PET/CT.

A 77-year-old man with a personal history of familial Mediterranean fever presented with a slowly enlarging tumefaction of the left abdominal wall and persistent inflammatory syndrome despite good adherence to colchicine. 18 F-FDG PET/CT showed a hypermetabolic muscular mass of the abdominal wall along with other hypermetabolic lesions including a peritoneal mass and several subcutaneous soft tissue nodules. CT-guided needle biopsy led to the diagnosis of a muscular localization of a malignant peritoneal mesothelioma, which is an extremely rare complication of familial Mediterranean fever. Six courses of chemotherapy with carboplatin and pemetrexed allowed an almost complete response.

Complete Heart Block as a Clinical Feature in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series of Three Cases

Background. Novel coronavirus-19 disease (COVID-19) is associated with significant cardiovascular morbidity and mortality. However, there have been very few reports on complete heart block (CHB) associated with COVID-19. This case series describes clinical characteristics, potential mechanisms, and short-term outcomes of critically ill COVID-19 patients complicated by CHB. Case Summary. We present three cases of new-onset CHB in critically ill COVID-19 patients. Patient 1 is a 41-year-old male with well-documented history of Familial Mediterranean Fever (FMF) who required mechanical ventilator support for acute hypoxic respiratory failure from severe COVID-19 pneumonia. He developed new-onset CHB without a hemodynamic derangement but subsequently had acute coronary syndrome complicated by cardiogenic shock. Patient 2 is a 77-year-old male with no past medical history who required intubation for severe COVID-19 pneumonia acute hypoxic respiratory failure. He developed CHB with sinus pause requiring temporary pacing but subsequently developed multiorgan failure. Patient 3 is 36-year-old lady 38 + 2 weeks pregnant, gravida 2 para 1 with no other medical history, who had an emergency Lower Section Caesarean Section (LSCS) as she required intubation for acute hypoxic respiratory failure. She exhibited new-onset CHB without hemodynamic compromise. The CHB resolved spontaneously after 24 hours. Discussion. COVID-19-associated CHB is a very rare clinical manifestation. The potential mechanisms for CHB in patients with COVID-19 include myocardial inflammation or direct viral infiltration as well as other causes such as metabolic derangements or use of sedatives. Patients diagnosed with COVID-19 should be monitored closely for the development of bradyarrhythmia and hemodynamic instability.

CARDIAC AA AMYLOIDOSIS SECONDARY TO FAMILIAL MEDITERRANEAN FEVER PRESENTING AS INTERMITENT COMPLETE HEART BLOCK: A RARE CASE WITH LITERATURE REVIEW

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Cardiac amyloidosis is rare but relatively more frequently seen with ATTR and AL types of amyloidosis. AA amyloidosis related cardiomyopathy or conduction abnormalities are rare owing to less frequent involvement of the myocardium in AA amyloidosis. We present a case of complete heart block in the setting of AA amyloidosis secondary to familial mediterranean fever. CASE PRESENTATION: A 50-year-old female with history of familial mediterranean fever (FMF) presented with syncopal episode. On presentation patient's vitals were stable, labs including TSH were within normal limits. Orthostatic vitals were positive. High-sensitivity troponins were negative with a normal EKG on presentation. Laterally displaced apical beat was noticed on examination. During hospitalization patient was noticed to have complete heart block that was not responsive to atropine and transcutaneous pacing however a response was noticed with epinephrine drip. TTE revealed heart failure with reduced ejection fraction of 41% with severe concentric left ventricular thickening typical for amyloid cardiomyopathy with a well-preserved E/A-wave, which is not usually seen in as thickened ventricle as patients. CRP and SAA were elevated. Patient had endomyocardial biopsy that confirmed amyloid deposition staining positive for amyloid AA and negative for TTR, kappa and lambda and a technetium pyrophosphate scan was also negative. A biventricular pacemaker was placed for complete heart block without adequate escape rhythm, which resulted in resolution of episodes of dizziness associated with bradycardia. Patient's FMF was managed with colchicine and anakinra with the help of rheumatology. Patient was started on diuresis during hospitalization and continued on discharge. Patient followed up with amyloidosis clinic after discharge. DISCUSSION: Systemic amyloidosis is rare and results from deposition of amyloid deposits in various organs and hence a wide range of effects. Prognosis may be vary with the type and extent of amyloidosis. More than 95% of cardiac amyloidosis is secondary to light chain/AL amyloidosis or transthyretin amyloidosis (ATTR), both genetic/hereditary and wild type.[1] Cardiac involvement from AA amyloidosis is very rare. Cardiac amyloidosis usually manifests with syncope or postural hypotension, which may be related with bradyarrhythmias.[2] Like the involvement of cardiovascular system, developments of arrhythmias are also common with ATTR type of amyloidosis as compared to other types and may require pacemaker placement. AA cardiac amyloidosis is rare and bradyarrhythmias or conduction system involvement has also been rarely reported. We report a rare case of complete heart block secondary to AA amyloidosis from familial Mediterranean fever requiring pacemaker placement. CONCLUSIONS: We present cardiac AA amyloidosis as a rare cause of syncope and orthostatic hypotension. Reference #1: Sipe, J.D., et al., Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid, 2016. 23(4): p. 209-213. Reference #2: Chamarthi, B., et al., Features and prognosis of exertional syncope in light-chain associated AL cardiac amyloidosis. Am J Cardiol, 1997. 80(9): p. 1242-5 DISCLOSURES: No relevant relationships by Usama Talib, source=Web Response

Pre-diagnostical Knowledge Did Not Provide Early Diagnosis in a Single-Center Turkish Familial Mediterranean Fever Cohort

Early diagnosis of familial Mediterranean fever (FMF) is crucial for preventing both recurrent attacks of polyserositis and complications in the course of the disease such as amyloidosis. Pre-diagnostical knowledge about the disease may assist early diagnosis. In this study, we evaluated the importance of pre-diagnostical knowledge about FMF for early diagnosis. We enrolled 138 FMF patients to the study. Then, the patients were dichotomized according to the patients’ FMF knowledge before diagnosis. We found that 40 (28.9%) of the patients were informed of the disease before diagnosis. Thirty-six of those patients got the data from their family members with FMF. Both demographic and disease-related features were similar between the groups. Furthermore, pre-diagnostic knowledge about FMF did not assist for early diagnosis of FMF. Interestingly, only half of the patients with history of FMF in family members were informed of the disease before diagnosis. Therefore, genetic consultation and patient education with questioning the patients for family history during medical evaluation may help early diagnosis in FMF.

Polyarteritis nodosa (PAN) associated with familial Mediterranean fever (FMF): An unusual case presentation and a review of the literature

IntroductionPolyarteritis Nodosa (PAN) is a rare systemic necrotizing vasculitis and the variety in clinical presentations lead to difficulty in diagnosis. The co-incidence of PAN disease and familial Mediterranean fever (FMF) has been reported and as they share similar clinical symptoms such as fever, abdominal pain, arthralgia, and skin rash the diagnosis could be challenging. Case reportThis report is presented as one of the unusual cases of PAN with intra-parenchymal renal aneurysm rupture, which was misdiagnosed as peri-renal abscess in a patient with FMF. Case presentationA 24 year–old Syrian man presented to the Emergency Department of Tishreen Hospital with fever (39 °C), anorexia, general weakness, severe musculoskeletal pain, weight loss and flank tenderness. He had a history of FMF since he was 7 years old and used to be treated with colchicine. Laboratory investigations revealed leukocytosis, anaemia, increased erythrocyte sedimentation rate (99 mm/1st h) and C-reactive protein (CRP) (96 mg/l). Renal function, urine analysis, creatinine clearance, electrolytes and transaminases were normal. Urine and blood culture were negative. The anti-neutrophil cytoplasmic antibody, rheumatoid factor and hepatitis markers were negative. On abdominal ultrasonography, renal parenchyma was hyper-echogenic with surrounding liquid. Antibiotics were provided with no improvement. The patient developed secondary hypertension and MRI brain revealed ischemic cortical and subcortical parietal lesions. PAN was diagnosed based on renal CT angiography showing multiple micro-aneurysms. Consequently, methylprednisolone pulses and cyclophosphamide were introduced with dramatic improvement. ConclusionIncreased awareness of such clinical association of PAN and FMF and early management may improve the disease outcome.

Neonatal onset familial Mediterranean fever

Objectives: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent, self-limited attacks of fever with serositis. Recently, it was shown that FMF patients with early disease onset have more severe disease. The aim of this study was to describe the demographic, clinical and genetic features of FMF patients who had disease onset during the neonatal period.Methods: Medical records of all patients diagnosed as FMF and had been seen in the outpatient clinic of Paediatric Rheumatology department between January 2013 and January 2014 were retrospectively evaluated. Patients with disease onset during the first month of life were included to the study.Results: Among 317 patients; 19 (12 males) were included to the study. Approximately 60% of the patients had family history of FMF. Homozygous p.M694V mutation was detected in 42% of the cases. Thirteen patients present with attacks of fever and remaining had attacks in the form of restlessness, resembling infantile colic starting in the neonatal period. Majority of these patients developed classical abdominal attacks between the ages of 1 and 2.5 years. The diagnosis of FMF was significantly delayed; the median age at onset of therapy was 3.5 years (range 7 months–17 years).Conclusion: Patients with FMF could have complaints even in the neonatal period. Homozygous p.M694V mutation is a prominent mutation in this group of patients. In order to prevent diagnostic delay physicians dealing with these type of patients should be more vigilant.

Redness From Fire: Fevers, Abdominal Pain, and Rash

Erythema ab igne (EAI) is an erythematous dermatosis that arises after repeated heat exposure. We present a case of EAI following chronic use of heating pads for analgesia. A 35-year-old woman with a history of familial Mediterranean fever (FMF), pancreatic exocrine insufficiency, presented to clinic for abdominal pain and fever. She presents to our GI clinic very frequently for FMF flares, which typically present as sharp abdominal pain with fevers, but this visit was unique for a new rash over her abdomen that was superficially nontender and nonpruritic. Over the years, the patient had been controlling her symptoms with colchicine, opioids, and heating pads. The abdominal exam was remarkable for mild tenderness to palpation diffusely, consistent with her previous flares. The overlying skin revealed a diffuse, nonblanching, hyperpigmented red/brown rash, sparing the periumbilical region and not extending into the flanks. Based on her well-known history, a diagnosis of EAI was made, and the patient was encouraged to avoid heating pads to that area. She has since decreased their use, and the discoloration persists but has improved.Erythema ab igne, or “redness from fire,” is a dermatosis that erupts on sites of repeated heat exposure. While historically associated with open fires, recent reports have implicated portable heaters, radiators, and even laptop computers. Two GI-related cases (gastroparesis and Crohn's disease), linked EAI with hot water bottles. The rash starts as a transient, reticulate, macular erythema, but with chronic heat exposure, becomes more livid and hyperpigmented. The heat is believed to cause superficial vasculature damage and dilation leading to erythema, and eventually, a more permanent hemosiderin and melanin deposition, which are presennt on biopsy and correlates to the darker hue. Usually, EAI resolves with avoidance of the causative heat source, although long-standing hyperpigmentation may persist for years. Reported treatments include topical 5-fluorouracil, bioflavonoids, trichloroacetic acid, and imiquimod. Biopsy is indicated if malignancy is suspected, as EAI has been rarely implicated in transformation into cutaneous squamous cell and Merkel cell carcinoma. Our case is particularly relevant to gastroenterologists since what can be an initially alarming abdominal rash that turns out to be a benign, self-resolving dermatosis, may at times end up serving as a clue for an underlying, more-serious GI issue.1852 Figure 1 No Caption available.

A case of myasthenia gravis accompanied with hasimato thyroiditis and familial mediterranean fever

Familial mediterranean fever (FMF), HasimatoA‚’s thyroiditis (HT) ve Myastenia gravis (MG) are chronical diseases that show autoimmunity. Literature reviews indicate several cases of coexisting MG and HT and only one case coexistence of MG and FMF. We present a clinical table of a 21-year-old male patient with all three diseases. The patient admitted to the hospital with limited eye movements, difficulty in swallowing which became evident towards the end of a meal. The patient had a history of FMF. The anti-TPO and anti-TG levels of the patient had increased. The ACh Receptor antibody was in the normal range (0.01), and the anti-MuSK value was high (>12). Single fiber EMG results of the patient were compatible with myasthenia gravis. The methylprednisolone and pyridostigmine treatment led to an almost complete improvement of the symptoms. As the patient had three different autoimmune disorders at once, it was thought to be a notable case worth presenting.

Approach to Growing Pains in Childhood in a Familial Mediterranean Fever Endemic Region

: Growing pain, still preserving its charm, is the most common form of recurrent musculoskeletal pain in childhood. Approach to diagnosis requires significant care in geographical regions with familial Mediterranean fever (FMF) endemicity. We discuss data and a current approach to growing pains in children in an FMF endemic region. The symptomatology may be confused with different diseases. Although unnecessary tests may be performed to reach diagnosis, sometimes patients may be misdiagnosed as having growing pain without revealing the primary underlying pathology. Definite algorithms are not developed for diagnosis of growing pains. Diagnosis is mainly based on typical clinical features of the condition. However laboratory tests and imaging methods may be used for diagnosis and differential diagnosis especially in atypical course suggesting diseases such as inflammatory ones or malignancies. Vitamin D deficiency should be investigated to give supplementation if necessary. Some helpful algorithms may be used in evaluation of patients. In order to evaluate myalgia as growing pain in areas where FMF is endemic, fever, abdominal pain, elevated acute phase reactants and history of FMF and/or amyloidosis in family should be carefully excluded. It is important to inform parents about the alarming symptoms of extremity pain and when to urge medical advice again.

Enthesitis in a 16-Year-Old Boy with M694V Mutation.

Introduction. FMF (Familial Mediterranean Fever) is characterized by recurrent attacks of fever and articular pain. Enthesitis is the hallmark of pain in spondyloarthropathy. Literature suggests association of M694V mutation and enthesitis. We report a case of a 16-year-old boy with enthesitis and FMF. Case Presentation. A 16-year-old boy of Turkish origin with a history of FMF presented with localized tenderness of the heel and severe disability. MRI showed an enthesitis of the plantar fascia. Standard treatment of FMF and enthesitis was not successful. After referral to a university hospital and expert opinion of a professor in rheumatology, this enthesitis should be treated as an enthesitis related arthritis. With this treatment, our patient fully recovered 8 months after the onset of the disease symptoms. Conclusion. M694V mutation related enthesitis should be considered in FMF patients with enthesitis. We would suggest treatment for enthesitis related arthritis in similar cases. This is of clinical importance because the treatment is different from treatment of enthesitis or articular pain caused by FMF.

L-ficolin and H-ficolin in patients with Familial Mediterranean fever

In the present study we performed comparative determination of the blood levels of L-ficolin and H-ficolin, opsonins and the initial components of the complement lectin pathway, in patients with Familial Mediterranean fever (FMF) in attack and attack-free periods and healthy subjects. In addition, in all study subjects serum levels of IL-1b and and total leukocyte count (TLC) were determined. Fifty FMF-affected subjects (female/male: 25/25; mean age ± SD: 31.3 ± 11; in attack/attack free: 23/27) and 81 age- and sex-matched healthy subjects (control group) without family history of FMF or other autoinflammatory diseases were enrolled in this study. Elevated H-ficolin level and TLC were detected in patients during attack period, whereas increased levels of L-ficolin and IL-1b were found in both attack and attack free patients with higher values during attack. Positive correlation between H-ficolin and L-ficolin levels in patients and healthy subjects was detected. Our results suggest excess production of L- and H-ficolins and increased apoptosis rate in FMF and indicate that H-ficolin is operating during development of acute autoinflammatory reactions, whereas L-ficolin is operating in both acute and subclinical autoinflammatory responses associated with this disease.

A brief history of familial Mediterranean fever.

[No Abstract Available] Saudi Med J 2015; Vol. 36 (9): 1126-1127 doi: 10.15537/smj.2015.9.12219

Penetrating heart injury in a case with pericardial adhesions

A 30-year-old male who was admitted to emergency department due to cutting and penetrating stab wounds had a 2 cm stab wound at the intersection of the right midclavicular line and 6th i ntercostals s pace. T here w as n o s ignificant finding on chest X-ray and echocardiography. Computed tomography (CT) which was performed to eliminate any other thoracic or mediastinal injury revealed a passage of contrast material from the right ventricle to the retrosternal space. The patient underwent median sternotomy urgently. After adhesions were removed in the patient with hematoma and pericardial adhesions, a 5 cm laceration along the sharp margin of the right ventricle was seen. The injury was repaired primarily with pledgeted 4/0 polypropylene sutures. The patient recovered without any complication. It was found that the patient with a history of familial Mediterranean fever (FMF) had asymptomatic pericarditis. Pericardial adhesions due to previous pericarditis limited severe cardiac injury by masking the echocardiographic findings. Echocardiography may not solely establish the extent of the involvement of cardiac chambers secondary to cutting and penetrating stab wounds towards the heart. In case of any clinical suspicion, CT contributes to the definitive diagnosis.

Frequency of alterations in the MEFV gene and clinical signs in familial Mediterranean fever in Central Anatolia, Turkey

Familial Mediterranean fever is a recessive autoinflammatory disease that is frequent in Armenians, Jews, Arabs, and Turks. The MEFV gene is responsible for this disease. We looked for MEFV gene variations (polymorphism and mutations) in a population that resides in Central Anatolia, Turkey. DNA was extracted from peripheral blood leukocytes of 802 familial Mediterranean fever patients. The DNA sequence data were examined for approximately 150 different mutations and polymorphisms, including single nucleotide polymorphisms in different exons of the MEFV gene. The male:female ratio of these patients was 1.44:1. Mutations were detected in 48.1% of the patients; 7.5% were homozygous, 11.1% were compound heterozygous and 31.5% had only one identifiable mutant allele. No mutations were detected in 51.9% of the patients. The main clinical characteristics of the patients were: abdominal pain in 20.6%, arthritis in 22.9% and amyloidosis in 4.6%. Sixty-six percent of patients had a family history of familial Mediterranean fever; 19.4% of the patients were found to have parental consanguinity. We conclude that the genetics of familial Mediterranean fever is more complex than has previously been reported; heterozygous patients presenting a severe phenotype should be further analyzed for less common secondary MEFV mutations, using gene sequencing.

Bone mineral density in familial Mediterranean fever

The aim of this study was to evaluate the bone mineral density (BMD) in familial Mediterranean fever (FMF) and to search the effects of genetic factors, family history of FMF and types of clinical attacks on BMD. Forty-four attack-free patients with FMF and 36 healthy voluntary subjects were included in the study. BMD measurements of lumbar spine and left proximal femur were performed by dual energy X-ray absorptiometry (DEXA). There was no statistically significant difference between patient and control groups regarding median values of lumbar BMD (P = 0.06), lumbar T (P = 0.08) and Z (P = 0.12) scores, femoral neck BMD (P = 0.13), femoral T (P = 0.22) and Z (P = 0.16) scores and total femur BMD (P = 0.14), T (P = 0.19) and Z (P = 0.27) scores. Patients with negative FMF family history had significantly lower femoral neck BMD (P = 0.018), femoral neck T (P = 0.009) and Z (P = 0.01) scores and total femur BMD (P = 0.033) than patients with positive FMF family history. There was no significant difference among the groups regarding mutation characteristic and types of attacks in lumbar BMD, T and Z scores, femoral neck BMD, T and Z scores and total femur BMD, T and Z scores (P > 0.05). We found that the bone loss of patients with FMF is not different from that of the controls. The increased bone loss in the patients with negative family history for FMF should be further investigated with larger patient groups taking into consideration of the risk factors related to family history for osteoporosis.

Malignant Peritoneal Mesothelioma in a Hemodialysis Patient with Familial Mediterranean Fever: A Case Report and Literature Review

Malignant mesothelioma is a rare tumor. The most common localization of mesothelioma is pleura. It rarely arises from the peritoneum. It has been suggested that familial Mediterranean fever (FMF) may cause the development of peritoneal mesothelioma. We describe a case of malignant peritoneal mesothelioma in a hemodialysis patient with FMF. The patient was a 56 year old female. A history of FMF was present since her childhood. She did not use colchicine and suffered from recurrent ascites. To the best of our knowledge, this is the seventh case of FMF diagnosed as having malignant peritoneal mesothelioma in the medical literature.

Renal amyloidosis in a child with sickle cell anemia

The kidney is frequently affected in patients with sickle cell syndrome, i.e., homozygous and heterozygous patients, with a consequently large spectrum of renal abnormalities that may range from minimal functional changes to chronic renal failure. Here, we present a 13-year-old boy with sickle cell anemia (SCA) (HbSS) who was referred to our unit with nephrotic syndrome. Renal biopsy revealed AA type amyloidosis on the basis of light microscopic findings, indicating Congo red staining and immunohistochemistry. He had neither a family history of familial Mediterranean fever (FMF) nor any complaint of recurrent abdominal pain, arthritis, and fever, but frequent painful vaso-occlusive crises. The patient was found to have no MEFV gene (Mediterranean feVer) mutations either. Painful episodic attacks might provoke recurrent acute inflammation, leading to repeated stimulation of acute phase responses and cause secondary amyloidosis. To our knowledge, this boy is the first case of SCA complicated by renal amyloidosis observed in childhood.

Infliximab Treatment of Familial Mediterranean Fever and Its Effect on Secondary AA Amyloidosis

We describe a patient with a long history of familial Mediterranean fever who developed proteinuria as a result of secondary AA amyloidosis. In this patient, the inflammatory process, including recurrent attacks of arthritis, abdominal pain, nephrotic syndrome secondary to amyloidosis, and high sedimentation rate, was rapidly suppressed by treatment with infliximab and there was remarkable improvement of the proteinuria.Because TNF-alpha is a proinflammatory cytokine that plays a major role in FMF and secondary amyloid, it is an appropriate target for therapy. Our case is the first case of reactive systemic amyloidosis secondary to familial Mediterranean fever, which responded favorably to infliximab.

Manifestations cutanées rares de la maladie périodique

Familial mediterranean fever belongs to the periodic fever syndromes. During the attacks, fever is associated with abdominal pain, arthralgia, or both. Cutaneous involvement occurs in 7 to 46 p. 100 of cases and mainly consists in erysipelas-like erythema. We report on three patients treated for familial Mediterranean fever who developed unusual cutaneous lesions. All the patients had long past history of familial mediterranean fever without cutaneous involvement except, for the third patient who had pseudo-erysipela. The first patient had diffuse Sweet's syndrome-like lesions, the second developed long lasting panniculitis of the thigh and the third had a persistent and lichenified erysipela-like plaque. In two patients, skin histology revealed an inflammatory infiltrate with neutrophils. In all cases, an increase in the colchicine dose led to the rapid resolution of the lesions. In our 3 case reports, the lesions were particular because of their atypical clinical appearance, their long duration, and they differed from the usual pseudo-erysipela aspect. Histopathologically, the lesions were similar to pseudo-erysipela, which has led some authors to hypothesize that cutaneous lesions of familial mediterranean fever belong to neutrophilic dermatoses. This hypothesis is supported by the response to the increase in colchicine doses.

Familial Mediterranean fever in the colchicine era: The fate of one family

In order to demonstrate the effect of prophylactic colchicine treatment on the natural history of familial Mediterranean fever (FMF), a family is presented with 6 out of 9 siblings affected by FMF. Each patient represents a different stage of the amyloidotic kidney disease of FMF and the effect of continuous colchicine treatment on its course. Considered together, the members of this family present an almost complete clinical, genetic, and behavioral picture of the disease.