Home About us Current issue Ahead of Print Back issues Submission Instructions Advertise Contact Login   

Search Article 
Advanced search 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 783 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 

Table of Contents   
Year : 2015  |  Volume : 26  |  Issue : 2  |  Page : 359-362
Microscopic polyangiitis associated with primary biliary cirrhosis, Sjogren's syndrome and Hashimoto's thyroiditis

Department of Internal Medicine, La Rabta Hospital, Tunis, Tunisia

Click here for correspondence address and email

Date of Web Publication3-Mar-2015


The association between microscopic polyangiitis (MPA) and primary biliary cirrhosis (PBC) has seldom been reported. We describe here a patient who presented with sensorimotor neuropathy along with hypothyroidism, renal failure and liver dysfunction. Detection of antinuclear antibodies at a titer of 1/800, anti-SSA, anti-SSB, anti-GP210, anti-microsomial and p-ANCA anti-myeloperoxydase antibodies along with renal, salivary and liver biopsy led to a diagnosis of MPA associated with PBC, Sjogren's syndrome and Hashimoto's thyroiditis.

How to cite this article:
Ghorbel I B, Belfeki N, Salem T B, Hamzaoui A, Khanfir M, Lamloum M, Miled M, Houman M H. Microscopic polyangiitis associated with primary biliary cirrhosis, Sjogren's syndrome and Hashimoto's thyroiditis. Saudi J Kidney Dis Transpl 2015;26:359-62

How to cite this URL:
Ghorbel I B, Belfeki N, Salem T B, Hamzaoui A, Khanfir M, Lamloum M, Miled M, Houman M H. Microscopic polyangiitis associated with primary biliary cirrhosis, Sjogren's syndrome and Hashimoto's thyroiditis. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2022 Dec 9];26:359-62. Available from: https://www.sjkdt.org/text.asp?2015/26/2/359/152515

   Introduction Top

Primary biliary cirrhosis (PBC) is a chronic inflammatory auto-immune disease that may be frequently associated with other rheumatic disorders such as Sjogren's syndrome, systemic sclerosis, rheumatoid arthritis or Hashimoto's thyroiditis. [1],[2] To the best of our knowledge, only two cases of microscopic polyangiitis (MPA) overlapping with PBC have been described. [3],[4]

   Case Report Top

A 62-year-old female patient was hospitalized when she presented with paresthesias in all four four limbs. She also complained of abdominal pain associated with chronic jaundice, dry eyes and asthenia for six months. Physical examination showed mucocutaneous jaundice, hepatomegaly, splenomegaly and edema of both lower limbs. Neurological examination revealed that she had an ataxic gait, bilateral glove and stocking-type sensory loss and impairment of position sense of the big toe. Tendon reflexes were weak in both the upper and the lower extremities. Blood counts revealed normocytic normochromic anemia with a hemoglobin of 8 g/dL. Coombs's test was negative. The liver parameters showed evidence of anicteric cholestasis. Creatinine was 13 mg/L and urine showed red cell casts and a 24-h proteinuria of 0.73 g. Serum protein electrophoresis showed a hypergammaglobulinemia (predominantly IgG). Thyroid function tests showed evidence of hypothyroidism The immunological tests revealed positive antinuclear antibodies (ANA) at a titer of 1/800 as well as positive anti-DNA, anti-SSA, anti-SSB, anti-GP210, anti-microsomial and p-ANCA anti-myeloperoxydase (MPO) antibodies, all tested by the enzyme-linked immunoassay (ELISA) method. The lupus band test was negative and complement was within normal limits. Cryoglobulin was reported to be negative. Serological tests for HIV and hepatitis B and C viruses were all negative. Anti-microsomal antibodies were positive, suggesting a diagnosis of Hashimoto's thyroiditis. Liver biopsy showed biliary ductular neogenesis, with a tendency to infiltrate the portal space and with vacuolar hepatocytes, confirming the diagnosis of PBC. Renal biopsy showed focal segmental glomerulonephritis with crescents. Salivary gland biopsy showed stage 4 chronic lymphocytic sialadenitis according to the Chisholm and Mason criteria. The electromyogram confirmed an axonal sensorimotor neuropathy of all four limbs and the nerve biopsy showed necrotizing vasculitis. A final diagnosis of PBC associated with MPA, Sjogren's syndrome and Hashimoto's thyroiditis was made. The patient underwent a course of corticosteroid treatment (1 mg/kg/day for 4 weeks with progressive tapering of the doses) along with monthly pulse infusions of cyclophosphamide (14 mg/kg/body surface area). There was marked improvement of the neurological symptoms along with normalization of the proteinuria. Her renal function did not get worse, she did not need renal replacement therapy and her liver function remained stable. Hypothyroidism was treated with levothyroxin. Sicca syndrome was symptomatically treated with artificial tears.

   Discussion Top

In about 56% of patients, PBC is associated with pulmonary involvement, mainly bronchial asthma, emphysema and decreased diffusion capacity, [5] but glomerulonephritis has seldom been reported. [6] It is noticeable that p-ANCA is present in 28% of patients with PBC and that its presence correlates with disease severity, [7] although its role in the pathogenesis of this condition is still a matter of debate. [3] MPA mainly affects small- and medium-sized vessels with alveolar and glomerular predilection. p-ANCA with anti-MPO antibodies are frequently, but not invariably, positive. [8]

Sjogren's syndrome is an auto-immune disease that chiefly targets the exocrine glands but occasionally extends to multiple organs such as the kidneys and nervous system. The typical pattern of renal disease associated with Sjogren's syndrome is tubulointerstitial nephritis with distal renal tubular acidosis. However, a review published in 2005 suggested that glomerulonephritis may account for up to 44% of cases of renal disease in patients with primary Sjogren's syndrome and may be associated with cryoglobulinemia in about half of cases. [9] In another study, anti-MPO p-ANCA has been reported to be positive in 26% of patients with Sjogren's syndrome. [10] Such features may explain the neurological and renal failure caused by vascular-mediated disease but cannot explain the liver disturbances associated with positive anti-glycoprotein-210 antibodies (AGPA 210) and liver biliary ductular neogenesis on liver biopsy.

Peripheral neuropathy, cresentic glomerulonephritis and a positive p-ANCA test may also be present in systemic lupus erythematosus. In our case, there were not enough criteria to diagnose lupus: hemolytic anemia was not present, lupus band test was negative and complement levels were within normal limits.

An association between PBC and MPA was first reported by Iannone et al in 2003. [3] They reported a 54-year-old Caucasian woman admitted with chronic polyarthritis and ischemic necrosis of the toe. Past medical history revealed paresthesias of the upper and lower limbs. On examination, livedo reticularis in the lower limbs and necrosis of the second left toe were present. A polyclonal hypergammaglobulinemia with increased concentrations of IgG, IgA and IgM and rising gamma-glutamyl transferase (GGT), was also present. Immunological assessment showed that antinuclear anti-bodies (ANA) (1/1600, speckled pattern) were positive. Likewise, anti-neutrophile cytoplasmic antibodies (p-ANCA), anti-myeloperoxydase antibodies and anti-cardiolipin IgG antibodies were detected. Anti-extractable nuclear antigens (anti-ENA) and anti-dsDNA antibodies were negative. Renal biopsy showed glomerulonephritis with abundant extracapillary cellularity (crescent formation) with sparse periglomerular myelomonocytic infiltrate, and segmental vascular fibrinoid necrosis. The immunofluorescence study revealed minimal deposits of immunoglobulins (IgG). These findings lead to the diagnosis of pauci-immune glomerulo-nephritis.

Three years later, because of persistently raised GGT, on further investigations, anti-mitochondrial antibodies (AMA) were detected by immunofluorescence (1/640, normal <1/40) as well as antigens M2 and M4 subtypes (normally absent). An associated PBC was suspected and a liver biopsy showed biliary ductular neogenesis, with a tendency to infiltrate the portal space and vacuolar hepatocytes confirming the diagnosis of PBC.

The second case was reported in 2006 by Luis Amezcua et al [4] concerning a 59-year-old woman with chronic dry cough and dyspnea. Chest computed tomography revealed mild to moderate diffuse pulmonary fibrosis with several nodules. An empirical therapeutic regimen, including prednisone 5 mg/day and bronchodilators, was started with resolution of symptoms. Two years later, she developed polyarthritis and sudden binocular diplopia secondary to extraocular polyneuropathy. Laboratory screening showed elevated alkaline phosphatase 966 U/L, aspartate aminotransferase 123 U/L and alanine aminotransferase 64 U/L p-ANCA (immunofluorescence 1/20), IgG antimitochondrial antibodies (AMA; immune-fluorescence 1/5120) and IgG anti-cardiolipin antibodies were detected, whereas RF, ANA, anti-dsDNA, and antibodies to extractable nuclear antigen were all negative. Liver histology showed a dense periductal inflammatory infiltration with active necrosis, periportal fibrosis and biliary ductal neogenesis. Kidney histology provided evidence of patchy tubular atro-phy, extracapillary hypercellularity (crescent formation) and segmental vascular fibrinoid necrosis with global sclerosis in 50% of the glomeruli, while immunofluorescence staining for IgG, IgM, IgA, C3 and C4 were all negative. The patient was treated with ursodeoxycholic acid, azathioprine 50 mg/day and prednisone 1 mg/kg/day with a rapid response. Three years later, she was hospitalized for fatigue and purpura in the lower limbs. Laboratory findings revealed microhematuria with more than 250 cells/μL, with a proteinuria of 812 mg/day. Treatment with oral prednisone and monthly pulse therapy with IV cyclophosphamide was started. Later, the patient developed oral and ocular dryness related with Sjogren's syndrome. There is currently no clear explanation for the simultaneous occurrence of both conditions Because of the scarcity of reports, it is not possible to establish either an overlap syndrome or a casual association. The relationship between PBC and MPA can be considered to be due to the possible contribution of the production of p-ANCA in the genesis of MPA. Further reports are necessary to clarify whether the coexistence between PBC and MPA is causal or casual. In addition, further studies are needed to understand the mechanisms underlying the association of PBC with other autoimmune conditions.

   References Top

Conn DL, Dickson ER, Carpenter HA. The association of Churg-Strauss vasculitis with temporal artery involvement, primary biliary cirrhosis, and polychondritis in a single patient. J Rheumatol 1982;9:744-8.  Back to cited text no. 1
Gentile M, Verta M, Vigna E, et al. Autoimmune hemolytic anemia concomitant with sequential autoimmune hepatitis-primary biliary cirrhosis overlap syndrome and Hashimoto's thyroiditis: a new entity of autoimmune polyendocrine syndrome. J Endocrinol Invest 2009; 32:287-8.  Back to cited text no. 2
Iannone F, Falappone P, Pannarale G, et al. Microscopic polyangiitis associated with primary biliary cirrhosis. J Rheumatol 2003;30: 2710-2.  Back to cited text no. 3
Amezcua-Guerra Luis M, Prieto P, Bojalil R, Pineda C, Amigo MC. Microscopic Polyangiitis associated with Primary Biliary Cirrhosis: A Causal or Casual Association? J Rheumatol 2006;33:2351-3.  Back to cited text no. 4
Uddenfeldt P, Bjerle P, Danielsson A, Nyström L, Stjernberg N. Lung function abnormalities in patients with primary biliary cirrhosis. Acta Med Scand 1988;223:549-55.  Back to cited text no. 5
Carella G, Marra L, Bevilacqua E. A case of membranous glomerulonephritis in the course of primary biliary cirrhosis. Am J Gastroenterol 1989;84:579-80.  Back to cited text no. 6
Mulder AH, Horst G, Haagsma EB, Limburg PC, Kleibeuker JH, Kallenberg CG. Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver diseases. Hepatology 1993;17:411-7.  Back to cited text no. 7
Sneller MC, Fauci AS. Pathogenesis of vasculitis syndromes. Med Clin North Am 1997; 81:221-42.  Back to cited text no. 8
Ramos-Casals M, Tzioufas AG, Font J. Primary Sjogren's syndrome: New clinical and therapeutic concepts. Ann Rheum Dis 2005;64:347-54.  Back to cited text no. 9
Gross WL, Schmitt WH, Csernok E. Antineutrophil cytoplasmic antibody associated diseases: A rheumatologist's perspective. Am J Kidney Dis 1991;18:175-9.  Back to cited text no. 10

Correspondence Address:
Dr. I Ben Ghorbel
Department of Internal Medicine, La Rabta Hospital, Tunis
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.152515

Rights and Permissions


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report

 Article Access Statistics
    PDF Downloaded797    
    Comments [Add]    

Recommend this journal