Long-term efficacy of tonsillectomy/adenotonsillectomy in patients with periodic fever aphthous stomatitis pharyngitis adenitis syndrome with special emphasis on co-existence of familial Mediterranean fever.

Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome is one of the most common autoinflammatory fever disorders in the childhood which may co-exists with familial Mediterranean fever (FMF) causing treatment complexity. As the role of surgery in PFAPA syndrome is still controversial, in this paper, our aim is to present our results of tonsillectomy/adenotonsillectomy in the treatment of PFAPA syndrome. Archives of a tertiary care hospital were investigated for patients who underwent tonsillectomy or adenotonsillectomy due to PFAPA Syndrome between 2010 and 2020. 344 patients were found but only 281 of them were accessible. Through phone call interview and chart review methods, preoperative and postoperative the number and severity of the attacks and general satisfaction after the operation were recorded and analyzed. Also, patients with concomitant FMF were analyzed separately. A total of 281 patients were included in the study. There was no improvement in 10 (3.55%) patients. Eight (2.84%) patients showed mild improvement, 29 (10.32%) patients had moderate improvement and 234 (83.27%) patients had full recovery after tonsillectomy. There were 266 PFAPA patients without FMF. No improvement, mild improvement, moderate improvement, and full recovery in this patient group were 5 (1.9%), 6 (2.3%), 25 (9.4%) and 230 (86.5%), respectively. FMF was present in 5.33% (15/281) of the patients. In PFAPA + FMF group 5 patients had no improvement (33.3%), 2 had mild improvement (13.3%), 4 had moderate improvement (26.7%) and 4 had full recovery (26.7%). Benefit of tonsillectomy was significantly lower in the patients with concomitant FMF when compared to the patients who did not have FMF (p < 0.001). Age of diagnosis, age of operation, severity of the disease, type of operation, and gender were found to have no significant relationship with the benefit from surgery (p < 0.05). According to the findings of this study, tonsillectomy is an effective long-term treatment for PFAPA syndrome with success rate of 83.27%. Also, preoperatively FMF should be considered in these patients, which dramatically reduces surgical efficacy.

Amyloid A Amyloidosis After Renal Transplantation: An Important Cause of Mortality.

BACKGROUND: There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients. METHODS: Eighty-one renal transplant recipients with FMF-associated AA amyloidosis (group 1) and propensity score-matched transplant recipients (group 2, n = 81) with nonamyloidosis etiologies were evaluated in this retrospective, multicenter study. Recurrence of AA amyloidosis was diagnosed in 21 patients (group 1a), and their features were compared with 21 propensity score-matched recipients with FMF amyloidosis with no laboratory signs of recurrence (group 1b). RESULTS: The risk of overall allograft loss was higher in group 1 compared with group 2 (25 [30.9%] versus 12 [14.8%]; P = 0.015 [hazard ratio, 2.083; 95% confidence interval, 1.126-3.856]). Patients in group 1 were characterized by an increased risk of mortality compared with group 2 (11 [13.6%] versus 0%; P = 0.001 [hazard ratio, 1.136; 95% confidence interval, 1.058-1.207]). Kaplan-Meier analysis revealed that 5- and 10-year patient survival rates in group 1 (92.5% and 70.4%) were significantly lower than in group 2 (100% and 100%; P = 0.026 and P = 0.023, respectively). Although not reaching significance, overall, 5- and 10-year graft survival rates (57.1%, 94.7%, and 53.8%, respectively) in group 1a were worse than in group 1b (76.2%, 95%, and 77.8%, respectively; P = 0.19, P = 0.95, and P = 0.27, respectively). CONCLUSIONS: AA amyloidosis is associated with higher risk of mortality after kidney transplantation. Inflammatory indicators should be monitored closely, and persistent high levels of acute-phase reactants should raise concerns about amyloid recurrence in allograft.

Outcomes of Canakinumab Treatment in Recipients of Kidney Transplant With Familial Mediterranean Fever: A Case Series.

Familial Mediterranean fever (FMF) is an important and preventable cause of chronic kidney disease due to secondary amyloidosis. Although colchicine is the first-line therapy in patients with FMF with 60% to 65% complete remission rates, 5% to 10% of patients are colchicine-resistant and 5% to 10% of them are intolerant to the therapy. Anti-interleukin-1 agents, such as anakinra and canakinumab, are safe and efficient therapeutic options in patients with colchicine resistance or intolerance. However, the data on management of these targeted agents is limited in recipients of kidney transplant (RKT). In this case series, we aim to share our experience on canakinumab therapy of 4 RKTs with FMF-related amyloidosis, who were followed up in our clinic between 2010 and 2017. All of the 4 patients with end-stage renal disease were colchicine- resistant and on other alternative therapies, which provided poor disease control. For efficient control of secondary amyloidosis, canakinumab therapy was initiated in 1 of the patients before the renal transplant, and for the remaining patients after renal transplant. Any serious adverse effect, development of proteinuria, or graft dysfunction has not been observed in any of the patients. Under the canakinumab treatment, complete clinical responses, prevent typical familial Mediterranean fever attacks with fever and arthritis and abdominal pain, normalized serum amyloid A and C-reactive protein levels were achieved in all patients. Canakinumab treatment is a safe and effective therapeutic option for RKTs with FMF who are resistant or intolerant to colchicine and anakinra.

Multiple pelvic cysts in a patient with familial Mediterranean fever: Benign cystic mesothelioma.

Benign cystic mesothelioma (BCM) is a rare tumor arising from endothelial cells of the pelvic visceral or parietal peritoneum. It is a clinically and histopathologically benign disease. Etiology and pathogenesis of BCM remain unclear. Familial Mediterranean fever (FMF) is an inherited disorder characterized by episodes of fever, and abdominal, chest and/or joint inflammation. Association between malignant mesothelioma and FMF has been reported previously; however, co-existence of FMF and BCM is rare. Here, we report a case of BCM in a 43-year-old male patient with FMF.

Successful treatment of familial Mediterranean fever with Anakinra and outcome after renal transplantation.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever and inflammation. The most severe complication of FMF is the development of AA amyloidosis, which can be life threatening. The only current effective treatment for FMF is colchicine. Regular prophylactic treatment with colchicine at a dose of 1-2 mg daily prevents or substantially reduces the clinical manifestations of FMF in at least 90% of cases. However, approximately 10% of patients are reported to be resistant or non-responsive to colchicine and in these cases there is no consensus as to which second line agents should be used. We describe the first case, to our knowledge, of a patient with FMF and end-stage renal failure due to AA amyloidosis, successfully treated with IL-1 receptor blockade. Our data suggest that the IL-1 receptor antagonist Anakinra (Kineret; r-metHuIL-1 ra) may represent a safe and effective therapy for the treatment of colchicine-resistant FMF, in patients requiring renal replacement therapy, with dialysis or transplantation.

[Infiltrating perineal and scrotal inflammation: rare cutaneous manifestation of familial Mediterranean fever or acne inversa?]. / Einschmelzende Entzündungen perineal und skrotal : Seltene kutane Manifestation bei Familiärem Mittelmeerfieber oder Acne inversa?

Familial Mediterranean fever (FMF) can present cutaneous symptoms. In the reported case, infiltrating perineal and scrotal inflammation were attributed to FMF and treated by systemic medication with colchicine. The poor outcome of this conservative approach and pathognomonic axillary dermatological findings allowed the diagnosis of acne inversa to be made. Knowledge of this clinical picture possibly including genital manifestations is crucial, as early excision of all affected regions is the therapy of choice that enables healing.

A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

OBJECTIVE: We carried out a prospective, randomized, controlled trial to clarify the effect of tonsillectomy on the clinical course of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. STUDY DESIGN: Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from 3 tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone. They were all followed up with symptom diaries for 12 months. Tonsillectomy was allowed after 6 months in the control group if the attacks recurred. RESULTS: Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group (50%) were free of symptoms (difference 50%, 95% confidence interval 23% to 75%, P < .001). Tonsillectomy was performed on 5/6 of the patients in the control group who still had symptoms after 6 months. The remaining unoperated child in the control group had recurrences of the fever episodes throughout the follow-up, but the symptoms became less severe, and the parents did not choose tonsillectomy. CONCLUSION: Tonsillectomy appeared to be effective for treating PFAPA syndrome. The fever episodes ceased without any intervention in half of the control subjects. We conclude that although the mechanisms behind this syndrome are unknown, tonsillectomy can be offered as an effective intervention for children with PFAPA.

Does colchicine have an antifibrotic effect on development of interstitial fibrosis in renal allografts of recipients with familial Mediterranean fever?

Colchicine, which has been reported to inhibit fibrosis, has been successfully used to treat fibrotic disorders, such as liver cirrhosis, scleroderma, and idiopathic pulmonary fibrosis. We hypothesized that besides its ability to prevent amyloid deposition, colchicine may prevent the development of interstitial fibrosis (IF) in amyloidosis patients who had undergone renal transplantation. We evaluated the influence of colchicine therapy on the development of IF in 25 patients with systemic amyloidosis secondary to familial Mediterranean fever (group 1). Twenty-five nonamyloidotic patients who did not receive colchicine therapy served as controls (group 2). The incidences of recurrence and development of IF in the first, second, and third years after transplantation were evaluated from follow-up allograft biopsies. Only four patients showed amyloid recurrence in their renal allografts. IF developed in 44% (11/25) of group 1 patients and 80% (20/25) of group 2 patients during the 36 months posttransplantation (P < .01). Development of IF in the first, second, and third years posttransplantation was significantly greater among group 2 recipients than group 1 recipients (P < .01). The overall 1-, 2-, and 3-year graft survival rates for group 1 recipients were 96%, 92%, and 80%, and those for group 2 recipients were 96%, 88%, and 60%, respectively. Our results support the thesis that colchicine therapy may help prevent the development of interstitial fibrosis in renal allografts.

Long-term outcome of renal transplantation in patients with familial Mediterranean fever amyloidosis: a single-center experience.

Although recurrence of amyloid A deposition in the allograft can be seen in patients with secondary amyloidosis due to familial Mediterranean fever (FMF), renal transplantation remains to be a choice of treatment for end-stage renal disease. The aim of this study was to determine short- and long-term results of renal transplantation in patients with FMF amyloidosis. We compared the outcomes of 17 patients with FMF amyloidosis among 431 (3.9%) transplants with 209 control patients. We observed 93% and 94% graft and patient survivals at 1 year, and 89% and 90% at 5 years. Also, the mean serum creatinine levels at 1 and 5 years posttransplant were similar. Recurrence of amyloidosis was documented in two allograft recipients presenting with nephrotic range proteinuria (12%), one of whom lost the allograft due to recurrence. Eleven patients had FMF gene analysis. The results of MEFV mutation analyses were: M694V/M694V homozygote in six patients, M694V/EQ148 in one patient, M694V/V726A in one patient, 680M-I/E148Q in one patient. FMF gene analysis was negative in two patients. Recurrence was noticed in one patient with M694V/M694V, while the other did not have an FMF gene analysis. Colchicine was reduced in nine patients due to side effects. In conclusion, the long-term outcomes of transplantation in patients with amyloidosis secondary to FMF is similar to that in the general transplant population and maintenance colchicine, even at low dose, appears to effectively prevent recurrence of amyloidosis in the allograft.

Hip involvement in patients with familial Mediterranean fever. A review of ten cases.

Hip involvement is uncommon in familial Mediterranean fever (FMF) and can result either from a process specific to this disease or from a coexisting chronic inflammatory joint disease, usually suggestive of ankylosing spondylitis (AS). We report ten cases of FMF with radiologically-documented inflammatory hip disease. Five patients had AS and one had juvenile idiopathic arthritis. There were six men and four women, with a mean age of 34.4 years +/- 17.6 (range, 15-70 years). Onset of the inflammatory hip disease occurred after bouts of acute hip symptoms in one of the patients with isolated FMF and after protracted hip arthritis in another; the two other patients had no history of hip symptoms. The HLA-B27 antigen was looked for in two of the five patients with FMF and AS, with negative results in both; another patient in this subgroup had severe ulcerative colitis. Total hip replacement or replacement of the acetabulum was required in six patients, including two with isolated FMF. Chronic joint disease has been estimated to contribute fewer than 5% of the joint manifestations in FMF. In previous studies, the hips and knees were affected in 75% of patients with chronic joint disease related to FMF. The association of FMF and AS (usually without the HLA-B27 antigen) has been well documented, although the pathogenic mechanisms that link these two conditions remain unknown.

Elective laparoscopic appendectomy in patients with familial Mediterranean fever.

Familial Mediterranean fever (FMF) also known as hereditary polyserositis, is an inherited disorder commonly found in Armenians, Turks, Arabs, Balkans, and Jews originating from North African countries. The diagnosis of FMF is based on clinical findings and family history, as no specific diagnostic test is yet available. One of its main clinical features is recurrent acute episodes of peritonitis. During such an episode, physical examination and laboratory findings may be similar to those for acute appendicitis. Therefore up to two-thirds of FMF patients undergo emergency appendectomy, with the appendix being normal in most cases. As laparoscopic appendectomy has proved to be safe and advantageous, and to prevent misdiagnosis and unnecessary emergency surgery, we performed elective laparoscopic appendectomy in 13 FMF patients ranging in age from 8 to 32 years. They had been suffering from the disease for 1 to 12 years (mean 3.8) and had had an average of 3.5 yearly episodes of FMF peritonitis. All procedures were concluded by laparoscopy without conversion to open surgery. The average postoperative hospital stay was 3.07 days. The only complication was superficial wound infection in one patient (7.6%), and the mean time to regain full normal activity was 8.5 days. We conclude that elective laparoscopic appendectomy in FMF patients is safe. It helps to exclude appendicitis as a cause for peritonitis in these patients and may prevent unnecessary emergency surgery.