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 Table of Contents  
Year : 2021  |  Volume : 11  |  Issue : 4  |  Page : 189-191

Multiple myeloma presented with renal failure in a patient with familial Mediterranean fever: Presentation of a rare association

1 Internal Medicine Department, Rheumatology and Immunology Unit, Mansoura University, Mansoura, Egypt
2 Internal Medicine Department, Mansoura University Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt

Date of Submission27-May-2021
Date of Decision15-Jun-2021
Date of Acceptance06-Jul-2021
Date of Web Publication21-Aug-2021

Correspondence Address:
Prof. Samar Tharwat
Mansoura University Hospital, El Gomhouria St, Mansoura, Dakahlia Governorate
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmrp.cmrp_50_21

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Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disorder characterised by repeated attacks of fever associated with polyserositis. The association between multiple myeloma (MM) and FMF has been rarely reported. Here, we describe a 39-year-old male with a long history of FMF presenting with acute kidney injury that has been proved to be caused by myeloma cast nephropathy. To the best of our knowledge, this is the fourth case to be reported with such association in the literature.

Keywords: Familial Mediterranean fever, multiple myeloma, renal failure

How to cite this article:
Tharwat S, Nassar MK. Multiple myeloma presented with renal failure in a patient with familial Mediterranean fever: Presentation of a rare association. Curr Med Res Pract 2021;11:189-91

How to cite this URL:
Tharwat S, Nassar MK. Multiple myeloma presented with renal failure in a patient with familial Mediterranean fever: Presentation of a rare association. Curr Med Res Pract [serial online] 2021 [cited 2022 Aug 12];11:189-91. Available from: http://www.cmrpjournal.org/text.asp?2021/11/4/189/324251

  Introduction Top

Familial  Mediterranean fever More Details (FMF) is the most common auto-inflammatory disease.[1] It is characterised by sporadic self-limited attacks of fever associated with serosal inflammation.[2] The disease is associated with mutations in the MEFV gene-encoding pyrin that causes excessive inflammatory reactions through uncontrolled production of interleukin-1.[3] Colchicine remains the main treatment of FMF, and the objective of treatment should be to prevent acute attacks and amyloidosis.[4]

Multiple myeloma (MM) is a specific form of haematological malignancies, with around 114,000 new cases worldwide per year.[5] It is the second most common adult hematologic malignancy, and the skeleton is the most commonly affected site.[5] The association between MM and FMF has been rarely reported. This paper aims to discuss an exuberant case of a long history of FMF presenting with renal failure which was found to be caused by myeloma cast nephropathy. Further investigations confirmed the diagnosis of MM.

  Case Report Top

A 39-year-old male was diagnosed with FMF 10 years earlier. The patient reported recurrent episodes of fever accompanied by abdominal and chest pain, significantly reduced by a daily dose of colchicine of 1.5 mg over the past 10 years.

On March 2020, the patient presented to the outpatient nephrology clinic complaining of gradually reduced amount of urine over the past month. On examination, he looked restless and anxious, not dehydrated or icteric. There was remarkable pallor with heart rate of 80 beats/min, respiratory rate of 18/min, temperature of 37.2°C and blood pressure of 170/100 mmHg. Systemic examination was unremarkable except for bilateral oedema of the lower limbs and hepatosplenomegaly.

Upon investigations, complete blood count revealed haemoglobin, WBCs and platelets count of 7.6 g/dl, 8.4 × 109/L and 374 × 109/L, respectively. The serum levels of creatinine, albumin and calcium were 11.4 mg/dl, 1.85 g/dl and 9.3 mg/dl, respectively. The erythrocyte sedimentation rate was markedly elevated (140 mm/h) and 24-h urinary protein excretion was 2 g/day. Liver enzyme and total bilirubin were within normal range. Serological tests for HCV, HBV and HIV were negative. The chest X-ray was found to be normal. Abdominal ultrasound showed hepatosplenomegally and both kidneys were normal. Renal biopsy was performed and revealed no glomerular abnormality, and the Congo red stain was negative. Interstitial fibrosis has been detected in more than 50% of the biopsied tissue and the renal tubules displayed an acute tubular injury with PAS negative casts surrounded by giant cells; a picture suggestive of myeloma cast nephropathy with no evidence of amyloidosis [Figure 1]. Serum protein electrophoresis showed increase in the beta-globulin fraction with a band of concentration (5.18 g/dl) suggesting monoclonal gammopathy [Figure 2]. Bone marrow aspirate was performed and demonstrated a heavy (>90%) infiltration by plasma cells. Flow cytometry and immunophenotyping were suggestive of MM as these cells showed positive expression for CD38, CD138 and CD56 and negative expression for CD27 and CD19. A skeletal survey revealed two well-defined lytic bone lesions, at the frontal bone of the skull and the body of third lumbar vertebra. The final diagnosis was MM in a male patient with FMF. Haemodialysis was initiated in view of uremic symptoms, and the patient was referred to the haematology outpatients' clinics and chemotherapy was started.
Figure 1: Renal biopsy shows acute tubular necrosis with myeloma cast nephropathy: (a) tubular necrosis with no abnormalities in glomerular basement membranes, cellularity or mesangium, (b) interstitial fibrosis of more than 50% of tissue biopsied, (c) acute tubular injury with PAS negative casts surrounded by giant cells

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Figure 2: Serum protein electrophoresis shows monoclonal band in the beta-globulin region

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  Discussion Top

We presented a case of a middle-aged male with a 10-year history of FMF who developed renal failure as a first presentation of MM. To the best of our knowledge, the association between MM and FMF is rarely reported in the world literature; only three cases with such association have been reported.[6],[7],[8]

FMF is the most common auto-inflammatory disorder.[9] Clinically, it is characterised by recurrent attacks of fever and serositis, often triggered by multiple environmental factors.[9] Renal dysfunction is amongst the most debilitating complications of FMF.[10] Renal dysfunction may be related to secondary amyloidosis or to other unusual non-amyloid glomerular diseases[11] such as IgG and IgM mesangial proliferative glomerulonephritis and IgA nephropathy.[11],[12]

MM is one of the most common haematological malignancies.[13] In patients with newly diagnosed MM, approximately one-third will present with estimated glomerular filtration rates <30 mL/min/1.73 m2 at the time of diagnosis.[13]

The pathogenesis of MM development in patients with FMF is unknown; however, it may be related to underlying immune-mediated mechanism or colchicine toxicity. In general, there is no evidence of increased incidence of cancer in FMF males under 50 years of age.[14] Older studies have identified a few cases of mesothelioma in FMF patients with no history of asbestos exposure, with speculation that repeated peritoneal or pleural inflammatory attacks may predispose to their growth.[15] Some reports indicated a co-occurrence of FMF and a group of malignancies, leading to the conclusion that FMF may be associated with increased risk of cancer.[16] Although there is no reported increase in FMF-related haematological cancers, the probability that heterozygous MEFV variants may be risk factors has been raised with overrepresentation in Turkish studies of myelodysplastic syndrome, myeloma and acute myeloid and lymphoid leukaemia.[17] Dysregulation of interleukin (IL-)1α or IL-1β production contributes to the pathogenesis of numerous auto-inflammatory disorders including FMF.[18] IL-1α has also emerged in recent years as an important cytokine in cancer pathogenesis.[19] Moreover, colchicine, the main treatment of FMF, is a neutral, liposoluble alkaloid that interferes with growth and mitosis of the microtubules.[20] Colchicine blocks mitosis and has been linked with haematological complications and leukaemia in rare cases.[21]

In the end, MM and FMF may have a common pathogenic pathway. This case highlights the association between MM with FMF and shades of light on non-amyloid kidney diseases that may occur in FMF patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that their names and initial will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Manna R, Rigante D. Familial Mediterranean fever: Assessing the overall clinical impact and formulating treatment plans. Mediterr J Hematol Infect Dis 2019;11:e2019027.  Back to cited text no. 1
Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967;43:227-53.  Back to cited text no. 2
Sönmez HE, Batu ED, Özen S. Familial Mediterranean fever: Current perspectives. J Inflamm Res 2016;9:13-20.  Back to cited text no. 3
Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med 1986;314:1001-5.  Back to cited text no. 4
Oyajobi BO. Multiple myeloma/hypercalcemia. Arthritis Res Ther 2007;9 Suppl 1:S4.  Back to cited text no. 5
Bashardoust B, Maleki N. multiple myeloma in a patient with familial Mediterranean fever. Iran J Kidney Dis 2017;11:388-91.  Back to cited text no. 6
Esquinas Blanco G, Jiménez Rojas C, Macías Montero MC, Rodríguez Heredia JM, Gallegos Cid A, García-Arroba J. Familial Mediterranean fever and myeloma: An undescribed association. Med Clin (Barc) 1992;98:61-3.  Back to cited text no. 7
Salem B, Afef F, Nadia B, Nabil A, Zouhir B, Maher B. Multiple myeloma occurring in a familial Mediterranean fever. Pan Afr Med J 2013;15:123.  Back to cited text no. 8
Boursier G, Hentgen V, Sarrabay G, Koné-Paut I, Touitou I. The changing concepts regarding the Mediterranean fever gene: Toward a spectrum of pyrin-associated autoinflammatory diseases with variable heredity. J Pediatr 2019;209:12-6.e1.  Back to cited text no. 9
Peleg H, Ben-Chetrit E. The kidney in familial Mediterranean fever. J Rheumatol 2013;40:1948-50.  Back to cited text no. 10
Akpolat T, Akpolat I, Karagoz F, Yilmaz E, Kandemir B, Ozen S. Familial Mediterranean fever and glomerulonephritis and review of the literature. Rheumatol Int 2004;24:43-5.  Back to cited text no. 11
Ceri M, Unverdi S, Altay M, Yılmaz R, Duranay M. An unusual effect of colchicine treatment in familial Mediterranean fever-associated glomerulonephritis. Rheumatol Int 2011;31:971-2.  Back to cited text no. 12
Hogan JJ, Alexander MP, Leung N. Dysproteinemia and the Kidney: Core Curriculum 2019. Am J Kidney Dis 2019;74:822-36.  Back to cited text no. 13
Twig G, Livneh A, Vivante A, Afek A, Shamiss A, Derazne E, et al. Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents. Ann Rheum Dis 2014;73:704-9.  Back to cited text no. 14
Ishak GE, Khoury NJ, Birjawi GA, El-Zein YR, Naffaa LN, Haddad MC. Imaging findings of familial Mediterranean fever. Clin Imaging 2006;30:153-9.  Back to cited text no. 15
Hartnett L, Egan LJ. Inflammation, DNA methylation and colitis-associated cancer. Carcinogenesis 2012;33:723-31.  Back to cited text no. 16
Oktenli C, Celik S. High frequency of inherited variants in the MEFV gene in patients with hematologic neoplasms: A genetic susceptibility? Int J Hematol 2012;95:380-5.  Back to cited text no. 17
Malik A, Kanneganti TD. Function and regulation of IL-1α in inflammatory diseases and cancer. Immunol Rev 2018;281:124-37.  Back to cited text no. 18
Bersudsky M, Luski L, Fishman D, White RM, Ziv-Sokolovskaya N, Dotan S, et al. Non-redundant properties of IL-1α and IL-1β during acute colon inflammation in mice. Gut 2014;63:598-609.  Back to cited text no. 19
Huang CS, Tsai JP, Chang HR. Colchicine-induced bone marrow aplasia in an elderly female with renal insufficiency. Acta Neurol 2010;24:53-6.  Back to cited text no. 20
Witwer MW, Schmid FR, Tesar JT. Acute myelomonocytic leukaemia and multiple myeloma after sulphinpyrazone and colchicine treatment of gout. Br Med J 1976;2:89.  Back to cited text no. 21


  [Figure 1], [Figure 2]


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