Mikulicz syndrome

Overview

Mikulicz syndrome is a rare condition characterized by the bilateral, painless enlargement of the lacrimal glands (located near the eyes) and salivary glands—particularly the parotid and submandibular glands. It presents with symptoms such as dry eyes and dry mouth, resembling other systemic conditions like Sjögren’s syndrome. Originally described by Jan Mikulicz-Radecki in the 19th century, Mikulicz syndrome was initially thought to be a distinct disorder. However, modern understanding classifies it more often as a manifestation of underlying systemic diseases rather than a standalone condition.

Today, the term "Mikulicz syndrome" is used descriptively rather than diagnostically and is often associated with other diseases such as sarcoidosis, lymphoma, IgG4-related disease, and tuberculosis. It is important to differentiate Mikulicz syndrome from "Mikulicz disease," which historically referred to a similar glandular enlargement without a known underlying cause.

Causes

Mikulicz syndrome is typically secondary to a systemic or autoimmune disease. The most common causes include:

• Sarcoidosis: A multisystem granulomatous disease that can affect the lacrimal and salivary glands.

• Sjögren’s syndrome: An autoimmune condition that targets moisture-producing glands, causing symptoms similar to Mikulicz syndrome.

• IgG4-related disease: A chronic inflammatory condition characterized by lymphoplasmacytic infiltration and fibrosis of affected organs, including salivary and lacrimal glands.

• Lymphoma: Particularly non-Hodgkin's lymphoma, which can cause glandular swelling.

• Tuberculosis: In rare cases, TB can present with chronic enlargement of the salivary or lacrimal glands.

In some cases, Mikulicz-like symptoms may occur without an identifiable systemic disease, but this is increasingly rare with advancements in diagnostic tools.

Symptoms

Symptoms of Mikulicz syndrome are primarily related to glandular enlargement and dysfunction. They may include:

Glandular Symptoms

• Painless, symmetrical swelling of the parotid, submandibular, and lacrimal glands

• Dry mouth (xerostomia)

• Dry eyes (keratoconjunctivitis sicca)

• Redness or irritation around the eyes due to lacrimal gland involvement

• Difficulty swallowing or speaking due to dry mouth

Systemic Symptoms (Depending on Underlying Cause)

• Fatigue or low-grade fever (especially in autoimmune diseases)

• Weight loss or night sweats (in cases related to lymphoma or tuberculosis)

• Joint pain or stiffness (in autoimmune diseases like Sjögren’s)

The course of the syndrome and associated symptoms largely depends on the underlying condition triggering the glandular involvement.

Diagnosis

Diagnosis of Mikulicz syndrome involves a thorough evaluation to identify the underlying cause. The approach includes:

• Clinical examination: Observation of gland enlargement and assessment of symptoms such as dry eyes and mouth

• Imaging studies: Ultrasound, CT scan, or MRI to assess the structure and size of salivary and lacrimal glands

• Lab tests:

  • Autoantibody tests (e.g., anti-SSA/Ro and anti-SSB/La for Sjögren’s)

  • Serum IgG4 levels (for IgG4-related disease)

  • Angiotensin-converting enzyme (ACE) levels (for sarcoidosis)

• Biopsy: Fine-needle aspiration or surgical biopsy of affected glands to detect inflammation, granulomas, lymphoid cells, or IgG4-positive plasma cells

• Tuberculosis screening: TB skin test or interferon-gamma release assay (IGRA) if infectious etiology is suspected

Accurate diagnosis is essential, as treatment depends entirely on the identification of the underlying condition.

Treatment

Treatment of Mikulicz syndrome is aimed at managing the root cause. Since the syndrome is a secondary manifestation, therapy is tailored based on the primary disease:

Autoimmune and Inflammatory Causes

• Glucocorticoids: Often first-line treatment for IgG4-related disease or sarcoidosis

• Immunosuppressive agents: Such as azathioprine, methotrexate, or mycophenolate mofetil in autoimmune conditions

• Hydroxychloroquine: Used in Sjögren’s syndrome for systemic symptoms and glandular involvement

Lymphoma

• Chemotherapy and/or radiotherapy as appropriate based on the type and stage of lymphoma

Tuberculosis

• Standard anti-TB antibiotic regimen for 6 to 9 months

Symptomatic Relief

• Artificial tears and saliva substitutes for dryness

• Good oral hygiene and regular dental check-ups to prevent caries and infections

• Pilocarpine or cevimeline (cholinergic agents) to stimulate saliva and tear production

Close monitoring and interdisciplinary management (involving rheumatologists, ophthalmologists, dentists, and ENT specialists) are often needed.

Prognosis

The prognosis of Mikulicz syndrome varies based on the underlying cause and the effectiveness of treatment. In many cases, early diagnosis and targeted therapy can lead to good control of symptoms and prevent progression. Prognostic factors include:

• IgG4-related disease: Often responds well to steroids, but relapse is common and requires long-term follow-up

• Sjögren’s syndrome: Chronic but manageable with supportive care; increased risk of lymphoma over time

• Sarcoidosis: Variable course; many cases resolve spontaneously or with treatment

• Lymphoma: Prognosis depends on the type and stage at diagnosis

With appropriate management, most patients with Mikulicz syndrome can achieve symptom control and maintain a good quality of life, although some may require lifelong monitoring and treatment.