Article Text

Download PDFPDF

IgG4 multiorgan lymphoproliferative syndrome as a differential diagnosis of primary Sjögren's syndrome in men?
  1. G Nocturne1,
  2. S Pavy1,
  3. T Lazure2,
  4. Y Taoufik3,
  5. C Miceli1,
  6. X Mariette1
  1. 1Department of Rheumatology, Université Paris-Sud 11, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
  2. 2Department of Pathology, Université Paris-Sud 11, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
  3. 3Department of Immunology, Université Paris-Sud 11, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
  1. Correspondence to X Mariette, Service de Rhumatologie, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France; xavier.mariette{at}

Statistics from

In 1888, Mikulicz-Radecki reported a case exhibiting bilateral, painless and symmetrical swellings of the lacrimal, parotid and submandibular glands. In 1953, Morgan and Castleman suggested that Mikulicz disease (MD) should be reconsidered as one of the manifestations of primary Sjögren's syndrome (pSS) as they shared many histopathological characteristics. But recently, several groups demonstrated that MD may differ from pSS. Actually, MD may partly be an IgG4-related systemic disease, the other components of which are still undelineated and include autoimmune pancreatitis, chronic sclerosing sialoadenitis, Riedel's thyroiditis, some cases of cholangitis, retroperitoneal fibrosis.1 Masaki defined a new clinical entity, the IgG4 multiorgan lymphoproliferative syndrome (MOLPS), which includes these manifestations.2 It is characterised by hyper-IgG4 γ-globulinaemia and IgG4 plasma cell infiltration. There are a number of differences with pSS: a sex ratio of 1:1, a less severe sicca syndrome, a better responsiveness to steroids and a lower prevalence of autoantibodies. As the distribution of involved organs and some of these features are close to the characteristics of pSS, such an entity could be a differential diagnosis of pSS, notably in men. After reporting the case of a woman responding to the diagnosis of IgG4 MOLPS, we reanalysed the data from 16 men and 18 women patients with sicca symptoms in order to assess whether some male patients could in fact have IgG4 MOLPS rather than pSS.

A 79-year-old woman was referred to our unit for a sicca syndrome associated with parotid gland enlargement. She had a history of autoimmune pancreatitis at the age of 25 years. Blood analysis showed positive antinuclear antibodies but negative anti-Sjögren's syndrome A/Sjögren's syndrome B antibodies. The labial salivary gland biopsy disclosed nodular lymphocytes infiltration (grade 4 of Chisholm classification). The patient fulfilled the American-European Consensus Group (AECG) criteria for pSS.3 To eliminate lymphoma, a biopsy of a cervical adenopathy was performed and showed an infiltration of IgG4+ plasma cells. The study of serum IgG subclasses showed a hyper-IgG4 γ-globulinaemia (IgG4=514 mg/dl) that confirmed the diagnosis of MOLPS. Oral prednisone therapy (0.7 mg/kg/day) led to prompt recovery with an important decrease in gland swelling. This case illustrates that IgG4 MOLPS can be a differential diagnosis of pSS.

We further analysed the data from 16 men referred to our unit for sicca symptoms and suspicion of pSS. As controls, we analysed the data from 18 women who fulfilled the AECG criteria for pSS. One (5%) of these women was Asiatic. All other patients were Caucasians. The characteristics of the patients and the results of examination are presented in table 1. Overall, none of the patients, out of the 16 male patients or the 18 female controls, fulfilled the MOLPS criteria.

Table 1

Characteristics of the patients

The limitations of the present study must be taken into account. First, we analysed a limited number of patients. Second, ethnic differences in incidence could be conceivable as most of the IgG4-related systemic diseases were reported by Japanese groups, but this result could be due to a misreading of this entity in the Caucasian population. Finally, we probably had a selection bias: all our patients had sicca symptoms, which are not so frequent in MOLPS (<40%1). None of our patients had a history of autoimmune pancreatitis, which is very common in MOLPS. On the contrary, the majority of our patients had positive antibodies, an unusual feature in MOLPS.

IgG4 MOLPS seems to be unusual in a French population of patients with pSS or a suspicion of pSS, even among male patients. Nevertheless, these results need to be confirmed by studies in more specific subsets of patients. Clinicians should be aware of this condition even in Caucasian patients with suspected pSS and negative autoantibodies.


View Abstract


  • Ethics approval This study was conducted with the approval of the CPP Bicêtre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.