First disclosure: Sjogren's syndrome coexists with these two diseases at the same time, and clinical vigilance is required

*For medical professionals only

The first case in the current literature in the report

Sjogren's syndrome (SS) is a diffuse connective tissue disease characterized by violations of exocrine glands such as tear glands and salivary glands, abnormal proliferation of B lymphocytes, and infiltration of histogenic lymphocytes

SS is associated with a variety of diseases, with rarer related diseases including lymphocytic interstitial pneumonia (LIP) and light chain deposition disease (LCDD

Case information

▌Clinical symptoms

70-year-old male, who was admitted to the Department of Respiratory Medicine

Past history includes stage 3 chronic kidney disease and gout

▌ Laboratory tests

Initial routine tests are normal, and autoimmune serology is strongly positive for anti-Ro/SSA and anti-LA/SSB antibodies in extractable nucleobron screening, while antinuclear antibody titer > 1:640

▌ Lung function test

Lung capacity is normal, with 115% (3.
21 liters) of the estimated forced expiratory volume and 113% (4.
12 liters)
of the estimated forced vital capacity.

Ventilation function was moderately impaired, and the diffusion coefficient of carbon monoxide was 57%
of the projected value.

▌ Imaging examination

X-rays of the chest show small diffuse parenchymal changes on both sides and blurred edges
of the heart.

HRCT shows nodular-cystic changes within the parenchyma of the lungs, both central and peripheral, small areas of hyperdense opacity on both sides, and interlobular thickening involving about 30% of lung tissue
.

This is highly suggestive of the possibility of interstitial lung disease (ILD), particularly LIP
.

In addition, there are non-LIP-specific nodules in the proximal bronchi of the lower right and upper right lobes
.

There are no other noteworthy extrapulmonary findings
.

Positron emission tomography (PET) did not show significant lesions
.

Figure 1 A: HRCT images show ground glass-like changes, cystic changes with perivascular distribution, and the presence of nodules and interlobular thickening
in the basal area.

B: Bronchial vascular distribution with highlighted nodules
.

▌ Tissue biopsy

Lacrimal gland biopsy confirmed SS, consistent with focal lymphocytic adenitis
.

Bronchoalveolar lavage (BAL) has a pronounced lymphocytosis (40%) to support the diagnosis
of LIP.

Histological examination of the right lower basal ganglion nodule biopsy shows chronic inflammation with no evidence
of malignancy or granulomas.

Positive PAS stain, positive light chain stain
.

Figure 2 A: Micrographs showing extracellular eosinophilic deposition of the matrix and blood vessel wall (H&E10×
).

B: POSITIVE PAS stain (10×
).

▌ Exclusionary checks

Since histology found the possibility of light chain and amyloidosis, hematological tests
were performed.

Complete blood count, myeloma screening, and electrophoresis are normal, and the urine is protein-negative
this week.

Serum free light chain tests were negative, including beta2 macroglobulin, with a normal κ:λ ratio of 0.
97
.

Bone marrow biopsy found no evidence
of hematologic malignancy.

To identify the cause of the patient's dyspnea, an echocardiogram is performed
.

Examination reveals significant ventricular bulge, left ventricular hypertrophy, and suggests an indoor conduction disorder, suggesting invasive heart disease
associated with the diagnosis of LCDD.

Holter monitoring shows 2:1 AV block and non-sustained ventricular tachycardia, and pacemakers
are required.

Cardiac magnetic resonance imaging (CMRI) shows limited systolic function, asymmetrical ventricular septal hypertrophy, and a maximum septal thickness of 25 mm
.

Hypertrophic ventricular septum without left ventricular outflow tract obstruction and diffuse patchy myocardial fibrosis
.

The results are thought to be more like hypertrophic cardiomyopathy (HCM) than invasive lesions
.

Figure 3: CMRI shows asymmetrical ventricular septal hypertrophy
.

Diagnostic process and differential diagnosis

• Idiopathic inflammatory myopathy: including myositis, dermatomyositis, etc.
  , with symmetrical proximal muscle weakness and elevated muscle enzymes as the main manifestations, the patient has normal muscle enzyme levels and no specific symptoms, so it is excluded
  .
  
  

• Systemic lupus erythematosus: more common in young women, often with fever, facial erythema, and joint swelling and pain
  .
  
  The patient's serology does not feature systemic lupus erythematosus and is therefore excluded
  .
  

• Malignancy: the patient's chest imaging has consistent features with LIP, however, the larger nodules are non-characteristic of LIP, and malignancy is a key differential diagnosis
  given his smoking history.
  
  Therefore, PET scans were performed and showed no cancerous features
  .
  

• Amyloidosis: biopsy of lung nodules in this patient shows light chain deposition, suggesting the possibility
  of amyloidosis, myeloma, and light chain deposition disease.
  
  PET has ruled out tumors, and professional institutions have ruled out amyloidosis
  .
  

• Determination of LIP and LCDD: characteristic BAL and imaging features to support the diagnosis
  of LIP.
  
  Since tumors and amyloidosis have been ruled out, LCDD is confirmed as the diagnosis
  of exclusion.
  
  Although there have been no previous reports of coexistence with LIP, the literature supports that LIP and LCDD alone have a strong correlation
  with SS.
  
  At this stage, patients receive treatment presumed to be SS with LCD and LIP, with a focus on ensuring that no extrapulmonary organs are involved
  .
  

• Exclusion of extrapulmonary organ involvement: renal failure is a feature of LCD, and most patients with LCDD develop progressive renal failure
  due to the deposition of light chains in tissues.
  
  This patient previously had chronic renal disease stage 3, but renal involvement is excluded due to the absence of proteinuria in urinalysis and the stability of the level of blood creatinine;
  

Cardiac insufficiency is another important manifestation of LCD, affecting up to 20% of patients with
LCD.

Given that the patient's dyspnea does not match his lung function tests, echocardiography is performed at the same time as The Holter ECG monitoring
.

Cardiac imaging experts believe that the patient's electrophysiological and CMRI results are more consistent with hypertrophic cardiomyopathy than with complications
of LCDD.

Rare complications of SS – LIP, LCDD

SS has multiple complications, and the organ or system damage caused by it is mainly concentrated in the blood system, respiratory system, urinary system, liver and so on
.

Among them, respiratory damage includes airway lesions, lung lesions, and vascular lesions ^[2].


Internationally, the incidence of SS lung damage is 9% to 20%, of which ILD is the most common
.

Domestic reports of hospitalized SS patients with lung lesions accounted for 42.
3%, while ILD accounted for 23.
3%, other manifestations of pulmonary bullae, pulmonary nodular shadow, pleural effusion, mediastinal lymphadenopathy and pulmonary hypertension
.

Figure 4: Affected organs of SS

Rarer associated diseases, including LIP and LCDD, can both be life-threatening and transform into lymphoma or multiple myeloma
, respectively.

■ LIP is a rare disease characterized by diffuse pulmonary lymphoplasmsis involving interstitium ^[3
].

It is a subtype of ILD and is distinctly different
from diffuse lung lymphoma.

Disease features include diffuse bronchial-associated lymphoid tissue hyperplasia and diffuse polyclonal lymphocyte infiltrates around the airways and spreads to the lung interstitium
.

LIP is usually accompanied by an autoimmune disease or HIV infection, and 50% of patients will be diagnosed with SS
.

■ LCDD is a rare disease in which monoclonal plasma cells or lymphoplasmic cells secrete abnormally, resulting in light-chain proteins deposited in tissues or organs in the form of non-amyloid substances, causing organ enlargement and impaired function ^[4
].

Among them, there are two main types of lung light chain deposition disease (PLCDD): nodular type and diffuse type
.

PLCDD may present with no abnormalities (normal lung function) or obstructive changes
.

Imaging manifestations include cysts, nodules, interstitial changes, and axillary and hilar lymphadenopathy
.

treat

In summary, patients are officially diagnosed with SS-communion LIP and LCDD
.

Due to the lack of data to guide the treatment of these patients, clinicians rely on basic principles to treat each individual disease process
.

Symptoms of dryness are controlled
with eye drops and hydration.

Treatment of LIP is mainly based on immunosuppression (glucocorticoids
).

From a respiratory point of view, the patient did not need treatment, and after the implantation of a biventricular pacemaker, his breathing difficulties improved
.

For LCDDs, special treatment is not required due to the exclusion of organ dysfunction caused by LCDDs
.

summary

SS is common, with an estimated 3 million patients worldwide, and is often associated with other autoimmune diseases, particularly rheumatoid arthritis, where lung symptoms are
frequent.

Separate cases have been reported of separate associations between LIP and LCDD and SS, but there are no guidelines, and this is the first publicly published case to indicate the coexistence of all three diseases
.

Managing patients with multiple autoimmune symptoms is a common clinical challenge, and multidisciplinary discussion is essential
.

This case highlights the underlying lung manifestations of Sjögren's syndrome, as well as the organ involvement and disease associations that LIP and LCDD may cause
.

[1]M.
Steward, J.
H.
Yu, and M.
A.
Gibbons, “Sjögren's syndrome as a cause of both lymphoid interstitial pneumonia and light chain deposition disease in a single patient,” BMJ Case Rep, vol.
15, no.
6 , Jun 24, 2022.

[2]J.
Mestre-Torres, and R.
Solans-Laque, “Pulmonary involvement in Sjögren's syndrome,” Med Clin (Barc), vol.
158, no.
4, pp.
181-185, Feb 25, 2022.

[3]F.
Luppi, M.
Sebastiani, M.
Silva, N.
Sverzellati, A.
Cavazza, C.
Salvarani, and A.
Manfredi, “Interstitial lung disease in Sjögren's syndrome: a clinical review,” Clin Exp Rheumatol, vol.
38 Suppl 126, no.
4, pp.
291-300, Jul-Aug, 2020.

[4]A.
V.
Arrossi, M.
Merzianu, C.
Farver, C.
Yuan, S.
H.
Wang, M.
O.
Nakashima, and C.
V.
Cotta, “Nodular pulmonary light chain deposition disease: an entity associated with Sjögren syndrome or marginal zone lymphoma,” J Clin Pathol, vol.
69, no.
6, pp.
490-6, Jun, 2016.

This article is from | Medical community rheumatic immunity channel

This article is written by | Zhou Zhici

This article is reviewed | Chen Xinpeng Deputy Chief Physician

Responsible Editor | tangerine