Introduction: Membranous glomerulonephritis is commonly described in systemic lupus erythematosus (SLE) and hypothyroidism.

Clinical presentation: We report a case of a 40-year-old woman who presented with a membranous glomerulonephritis associated with SLE, rheumatoid arthritis and hypothyroidism due to Hashimoto’s thyroiditis.

Conclusions: The simultaneous occurrence of these three diseases as possible causes of membranous glomerulonephritis is extremely exceptional

Aydi, Zohra

Baili, Lilia

Ben Dhaou, Basma

Boussema, Fatma

Daoud, Fatma

Kochbati, Samir

Rachdi, Imène

Introduction: Membranous glomerulonephritis is commonly described in systemic lupus erythematosus (SLE) and hypothyroidism.
 Clinical presentation: We report a case of a 40-year-old woman who presented with a membranous glomerulonephritis associated with SLE, rheumatoid arthritis and hypothyroidism due to Hashimoto’s thyroiditis.
 Conclusions: The simultaneous occurrence of these three diseases as possible causes of membranous glomerulonephritis is extremely exceptional

Lilia Baili

Imène Rachdi

Fatma Daoud

Zohra Aydi

Basma Ben Dhaou

Samir Kochbati

Fatma Boussema

Directory of Open Access Journals

 	  Doi:	  10.12890/2014_000122	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   European	  Journal	  of	  Case	  Reports	  in	  Internal	  Medicine	   	  	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   ©	  EFIM	  2014	  Simultaneous	  Occurrence	  of	  Systemic	  Lupus	  Erythematosus,	  Rheumatoid	  Arthritis,	  	   Hashimoto’s	  Thyroiditis	  and	  Membranous	  Glomerulonephritis	  Lilia	  Baili,	  Imène	  Rachdi,	  Fatma	  Daoud,	  Zohra	  Aydi,	  Basma	  Ben	  Dhaou,	  Samir	  Kochbati,	  Fatma	  Boussema	  	  Internal	  Medicine	  Department,	  Habib	  Thameur	  Hospital,	  Tunis,	  Tunisia	  	  Abstract	  	  Introduction:	   Membranous	   glomerulonephritis	   is	   commonly	   described	   in	   systemic	   lupus	   erythematosus	   (SLE)	   and	  hypothyroidism.	   	  	  Clinical	  presentation:	  We	  report	  a	  case	  of	  a	  40-­‐year-­‐old	  woman	  who	  presented	  with	  a	  membranous	  glomerulonephritis	  associated	  with	  SLE,	  rheumatoid	  arthritis	  and	  hypothyroidism	  due	  to	  Hashimoto’s	  thyroiditis.	  	  Conclusions:	   The	   simultaneous	   occurrence	   of	   these	   three	   diseases	   as	   possible	   causes	   of	   membranous	  glomerulonephritis	  is	  extremely	  exceptional.	  	   	  Keywords:	  Systemic	  lupus	  erythematosus,	  rheumatoid	  arthritis,	  Hashimoto’s	  thyroiditis,	  membranous	  glomerulonephritis,	  overlap	  syndrome	  	  	  Introduction	  Membranous	  glomerulonephritis,	  described	  as	  Class	  V	  of	  lupus	  nephritis,	  is	  rarely	  observed	  in	  rheumatoid	  arthritis	  (RA)	  and	  Hashimoto’s	  thyroiditis	  [1–3].	   	  We	   report	   an	   interesting	   case	  of	   concomitant	   systemic	   lupus	   erythematosus	   (SLE),	   RA,	  Hashimoto’s	   thyroiditis	   and	   a	  membranous	  glomerulonephritis.	  	  Case	  report	   	  A	  40-­‐year-­‐old	  woman	  with	  no	  medical	  past	  history	  was	  referred	  for	   limb	  oedema	  and	   inflammatory	  arthralgia	  for	  the	  previous	   6	   months.	   Physical	   examination	   revealed	   diffuse	   oedema,	   synovitis	   of	   proximal	   interphalangeal	   and	  Received:	  30/07/2014	  Accepted:	  24/10/2014	  Published:	  11/11/2014	  How	  to	  cite	  this	  article:	  Baili	  L,	  Rachdi	  I,	  Daoud	  F,	  Aydi	  Z,	  Ben	  Dhaou	  B,	  Kochbati	  S,	  Boussema	  F.	  Simultaneous	  Occurrence	  of	  Systemic	  Lupus	  Erythematosus,	  Rheumatoid	  Arthritis,	  Hashimoto’s	  Thyroiditis	  and	  Membranous	  Glomerulonephritis.	  EJCRIM	  2014;1:doi:	  10.12890/2014_000122	  Conflicts	  of	  Interests:	  The	  authors	  declare	  that	  they	  have	  no	  conflicts	  of	  interest	  related	  to	  this	  research.	  	   	  Doi:	  10.12890/2014_000122	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   European	  Journal	  of	  Case	  Reports	  in	  Internal	  Medicine	   	  	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   ©	  EFIM	  2014	  metcarpo-­‐phalangeal	   joints	  and	  thyroid	  goitre.	  Her	  blood	  pressure	  was	  120/80	  mmHg.	  Biological	  examination	  showed	  normocytic	   anaemia	   (haemoglobinaemia=9.1	   g/l),	   lymphopenia	   (lymphocyte	   count	   1300/mm3),	   hypoprotidaemia	   (28	  g/l),	   hypoalbuminaemia	   (9.4	   g/dl)	   with	   serum	   creatinine	   at	   89	   μmol/l	   (creatinine	   clearance	   60	   ml/min),	  hypercholesterolaemia	   (13.3	  mmol/l)	   and	   hypertriglyceridaemia	   (9.6	  mmol/l).	   Urinary	   examination	   revealed	  massive	  proteinuria	  (8.85	  g/24	  h),	  leucocyturia	  (400/mm3)	  and	  haematuria	  (69/mm3).	  TSH	  level	  was	  elevated	  at	  16.3	  mUI/l	  (0.2–5)	  and	  FT4	  was	   low	  at	  5	  pmol/l	   (6–23).	   Serological	   tests	  of	  viral	  hepatitis	  B	  and	  C,	  HIV,	  EBV	  and	  CMV	  were	  negative.	  Complement	  was	  consumed	  (C3,	  0.73	  g/l;	  C4,	  0.14	  g/l).	  Antinuclear	  antibodies	  (ANA)	  and	  DNA	  antibodies	  were	  positive	  (ANA=1/320	  controlled	  1/1200	  homogeneous	  speckled;	  DNA	  antibodies:	   IFA	  Crithidia	   lucilae	  +++,	  ELISA	  +++;	  ENT:	  anti	  Sm+,	  antinucleosome	  +).	  Rheumatoid	  factors	  (RF,	  187	  UA/ml	  (N<30)	  and	  anticyclic	  citrullinated	  peptide	  antibodies	  were	  positive	  (anti	  CCP,	  98	  U/ml	  (N<25)).	  Anti-­‐thyroglobulin	  antibodies	  were	  positive	  at	  high	  titre	  (980	  UI/ml;	  normal	  ≤	  100).	  Cervical	  ultrasound	  revealed	  a	  multinodular	  goitre.	  A	  diagnosis	  of	  Hashimoto’s	  thyroiditis	  was	  then	  made.	  X-­‐rays	  of	  the	  wrists	   showed	  severe	  carpitis.	  The	  diagnosis	  of	  SLE	  was	   retained	  considering	   four	  ACR	  criteria:	   lymphopenia,	  positive	  ANA,	  positive	  anti-­‐DNA	  and	  proteinuria.	  A	  diagnosis	  of	  RA	  was	  made	  based	  on	  distal	  joint	  synovitis,	  radiological	  carpitis	  and	  positive	   immunological	   tests.	  A	  percutaneous	   renal	  biopsy	  was	  performed	  and	   the	  histopathological	  examination	  showed	  a	  membranous	  glomerulonephritis	  with	  focal	  mesangial	  proliferation	  and	  segmental	  hyalinosis	  (Figs.	  1	  and	  2).	  Immunoglobulin	   type	   G	   and	   M,	   complement	   (C3,	   C1q)	   and	   fibrinogen	   deposits	   were	   detected	   on	   standard	   direct	  immunofluorescence.	  	  The	  patient	  was	   treated	  with	   intravenous	  boli	  of	  methylprednisolone	   relayed	  with	  oral	   corticosteroids	  at	  a	  dose	  of	  1	  mg/kg/day.	  Immunosuppressive	  treatment	  with	  six	  bimensual	  boli	  of	  cyclophosphamide	  relayed	  with	  azathioprine	  was	  also	  performed.	  She	  was	  also	  treated	  with	  thyroid	  hormones.	  The	  outcome	  was	  favourable,	  marked	  by	  an	  improvement	  of	   the	  oedema	  and	  a	  normalization	  of	   thyroid	  hormone	   levels.	  Urine	  analysis	   showed	   regression	  of	  proteinuria	   (0.23	  g/24	  h).	  	  	  Figure	  1:	  Photo	  of	  the	  histopathological	  examination	  of	  kidney	  biopsy	  (Trichrome	  Masson,	  magnification	  400×):	  membranous	  glomerulonephritis	  with	  focal	  mesangial	  proliferation.	  Figure	  2:	  Photo	  of	  histopathological	  examination	  of	  kidney	  biopsy	  (silver	  staining):	  membranous	  glomerulonephritis	  and	  spikes.	   	   	  Doi:	  10.12890/2014_000122	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   European	  Journal	  of	  Case	  Reports	  in	  Internal	  Medicine	   	  	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   ©	  EFIM	  2014	  Discussion	  Membranous	   glomerulonephritis	   is	   a	   pattern	   of	   injury	   that	   results	   from	   subendothelial	   and	  mesangial	   deposition	   of	  immunoglobulins	  caused	  by	  persistent	  antigenaemia	  and/or	  circulating	  immune	  complexes	  [4].	  It	  is	  typically	  classified	  as	  idiopathic	  or	  secondary	  to	  infections,	  drugs,	  toxins,	  malignancy	  or	  autoimmune	  disease	  especially	  to	  SLE.	   	   	  In	  this	  case,	  we	  analyze	  the	  occurrence	  of	  membranous	  glomerulonephritis	  in	  a	  patient	  with	  three	  autoimmune	  diseases.	  Autoimmune	  disorders	  can	  be	  organ-­‐specific	  or	  they	  can	  involve	  multiple	  organs.	  The	  common	  characteristic	  of	  all	  these	  disorders	  is	  the	  production	  of	  different	  autoantibodies	  against	  various	  autoantigens	  along	  with	  inflammation.	   	  Membranous	  glomerulonephritis	  represents	  about	  20%	  of	  clinically	  significant	  renal	  disease	  in	  SLE	  [1].	  Few	  studies	  have	  directly	   addressed	   the	   pathogenesis	   of	   membranous	   glomerulonephritis.	   Natural	   history	   studies	   of	   membranous	  glomerulonephritis	   in	   SLE	   suggest	   a	   relatively	   low	   rate	   of	   progression	   to	   end-­‐stage	   renal	   disease	   but	   a	   high	   rate	   of	  significant	   comorbidities	   [5].	   Considering	   the	   nephrotic	   syndrome,	   the	   patient	   was	   treated	  with	   immunosuppressive	  therapies,	  including	  corticosteroids	  and	  cyclophosphamide.	   	  Renal	   involvement	   during	   RA	   is	   rare	   [6].	   Renal	   lesions	   directly	   due	   to	   the	   disease	   itself	   are	   infrequent.	   Regarding	  membranous	  glomerulonephritis,	  the	  relationship	  between	  with	  RA	  remains	  unclear.	  Membranous	  glomerulonephritis	  is	   generally	   accepted	   as	   the	  most	   frequent	   histological	   lesion	   during	   treatment	   with	   gold	   salts,	   D-­‐penicillamine	   and	  bucillamine,	   although	   other	   authors	   have	   described	   a	   direct	   relationship	   with	   RA	   [2,	   7].	   Membranous	  glomerulonephritis	  had	  occurred	  in	  our	  patient	  before	  beginning	  treatment.	  So,	  it	  may	  be	  directly	  related	  to	  RA.	  In	  fact,	  even	  if	  the	  pathogenesis	  of	  membranous	  glomerulonephritis	  in	  RA	  is	  still	  unknown,	  it	  is	  hypothesized	  that	  the	  presence	  of	  circulating	   immune	  complexes	  and	  rheumatoid	  factor,	  or	  alteration	   in	  T	  cell	   immune	  response	  and	  the	  presence	  of	  proinflammatory	  cytokines,	  may	  have	  played	  a	  role	  in	  the	  pathogenesis	  of	  the	  nephropathy.	  Thyroid	   pathology	   has	   a	   high	   prevalence	   in	   the	   general	   population,	   although	   autoimmune	   aetiology	   is	   rare.	   It	   is	  associated	   with	   a	   variety	   of	   glomerulonephritis	   types	   in	   very	   few	   cases,	   the	   most	   frequent	   being	   membranous	  glomerulonephritis	  [8].	  As	  reported	  by	  some	  authors,	  simultaneous	  occurrence	  of	  thyroid	  and	  glomerular	  disease	  could	  be	   explained	   by	   the	   existence	   of	   an	   autoimmune	   pathogenesis	   common	   to	   both	   conditions,	   and	   incidence	   could	   be	  higher	  than	  suspected,	  with	  proteinuria	  being	  found	  in	  a	  high	  proportion	  of	  patients	  with	  autoimmune	  thyroiditis	  and	  Graves’	  disease	  [8–10].	   In	  our	  case,	  thyroiditis	  was	  diagnosed	  based	  on	  positive	  antithyroid	  antibodies,	  and	   its	  clinical	  manifestation	  was	  a	  clinical	  hypothyroidism.	  The	  parallelism	  seen	  between	  remission	  of	  nephrotic	  syndrome	  and	  TSH	  normalization	  under	   treatment	  with	   thyroid	  hormone	  and	  corticosteroids	  should	  be	  noted.	  So,	   in	  cases	  of	  apparently	  idiopathic	  nephrotic	   syndrome,	   thyroid	   function	  needs	   to	  be	   investigated	   [9,	   10].	  Membranous	  glomerulonephritis	   in	  this	  case	  is	  probably	  secondary	  to	  autoimmune	  disorders	  caused	  by	  the	  exceptional	  simultaneous	  occurrence	  of	  these	  three	  autoimmune	  diseases.	  	  Learning	  Points	  	  • Lupus	  is	  a	  classical	  aetiology	  of	  membranous	  glomerulonephritis.	  • Membranous	  glomerulonephritis	  is	  an	  uncommon	  extra-­‐articular	  manifestation	  of	  rheumatoid	  arthritis.	   	  • Autoimmune	  thyroiditis	  with	  nephrotic	  syndrome	  is	  marked	  by	  predominant	  membranous	  glomerulonephritis.	   	   	  Doi:	  10.12890/2014_000122	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   European	  Journal	  of	  Case	  Reports	  in	  Internal	  Medicine	   	  	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   	   ©	  EFIM	  2014	  • It	  is	  necessary	  to	  perform	  an	  analysis	  of	  the	  thyroid	  hormones	  in	  every	  patient	  with	  nephrotic	  syndrome	  as	  part	  of	  an	  aetiological	  screening	  process.	  • The	  simultaneous	  occurrence	  of	  these	  three	  diseases	  as	  possible	  causes	  of	  membranous	  glomerulonephritis	   is	  extremely	  rare.	  	  References	  	  1. Mok	   CC.	  Membranous	   nephropathy	   in	   systemic	   lupus	   erythematosus:	   a	   therapeutic	   enigma,	   Nat	   Rev	   Nephrol	  2009;5:212–220.	  2. Maruotti	  N,	  Corrado	  A,	  Gaudio	  A,	  Cantatore	  FP.	  Membranous	  nephropathy	  in	  rheumatoid	  arthritis:	  a	  case	  report,	  Clin	  Exp	  Rheumatol	  2009;27:840–842.	  3. Weetman	  AP,	  Tomlinson	  K,	  Amos	  N,	  Lazarus	  JH,	  Hall	  R,	  McGregor	  AM.	  Proteinuria	  in	  autoimmune	  thyroid	  disease,	  Acta	  Endocrinol	  1985;109:341–347.	  4. Sethi	  S,	  Fervenza	  FC.	  Membranoproliferative	  glomerulonephritis:	  pathogenetic	  heterogeneity	  and	  proposal	  for	  a	  new	  classification,	  Semin	  Nephrol	  2011;31:341–348.	  5. Austin	  HA,	  Illei	  GG.	  Membranous	  lupus	  nephritis,	  Lupus	  2005;14:65–71.	  6. Stokes	  MB,	  Foster	  K,	  Markowitz	  GS,	  Ebrahimi	  F,	  Hines	  W,	  Kaufman	  D	  et	  al.	  Development	  of	  glomerulonephritis	  during	  anti-­‐TNF-­‐α	  therapy	  for	  rheumatoid	  arthritis,	  Nephrol	  Dial	  Transplant	  2005;20:1400–1406.	  7. Baba	   N,	   Nomura	   T,	   Sakemi	   T,	   Uchida	   M,	   Watanabe	   T.	   Membranous	   glomerulonephritis	   probably	   related	   to	  bucillamine	  therapy	  in	  two	  patients	  with	  rheumatoid	  arthritis,	  Nippon	  Jinzo	  Gakkai	  Shi	  1991;33:629–634.	  8. Esteve	   V,	   Fontseré,	   Taurina	   A,	   Ramirez	   M.	   Enfermedad	   de	   Graves,	   hipotiroidismo	   farmacológico	   y	   síndrome	  nefrótico	  por	  enfermedad	  de	  cambios	  mínimos,	  Nefrología	  2008;28:230–231.	  9. Valentín	   M,	   Bueno	   B,	   Gutiérrez	   E,	   Martínez	   A,	   González	   E,	   Espejo	   B	   et	   al.	   Glomerulonefritis	  membranoproliferativa	  hipocomplementémica	  asociada	  a	  tiroiditis	  autoinmune,	  Nefrología	  2004;24:43–48.	   	  10. Nishiki,	  Murakami	  Y,	  Yamane	  Y,	  Kato	  Y.	  Steroid-­‐sensitive	  nephrotic	  syndrome,	  sarcoidosis	  and	  thyroiditis:	  a	  new	  syndrome?	  Nephrol	  Dial	  Transplant	  1999;14:2008–2010.	  	  	  

European Journal of Case Reports in Internal Medicine

Simultaneous Occurrence of Systemic Lupus Erythematosus, Rheumatoid Arthritis, Hashimoto’s Thyroiditis and Membranous Glomerulonephritis

Scientific Open-access Literature Archive and Repository

Crossref

Simultaneous Occurrence of Systemic Lupus Erythematosus, Rheumatoid Arthritis, Hashimoto’s Thyroiditis and Membranous Glomerulonephritis

Abstract

Similar works

Full text

Available Versions

Directory of Open Access Journals

Scientific Open-access Literature Archive and Repository

Crossref