ABSTRACT
The incidence of light chain deposition disease (LCDD) is relatively low and difficult to diagnose, while cases of PLCDD combined with Sjogren's syndrome are more rare. A case of pulmonary light chain deposit disease combined with Sjogren's syndrome admitted to our department is reported as follows, and the relevant literature is reviewed in order to improve clinicians' understanding of rare diseases and early diagnosis and treatment.
Keywords: pulmonary light chain deposition disease, severe haemoptysis, Sjögren syndrome
Light chain deposition disease (LCDD) is a non‐amyloid monoclonal immunoglobulin light chain deposition disorder. It is usually secondary to lymphoproliferative diseases, such as multiple myeloma, B‐cell lymphoma, and some secondary to autoimmune diseases like Sjögren syndrome (SS). This study presents a case of PLCDD associated with SS admitted to our hospital and reviews the relevant literature.
1. Introduction
Light chain deposition disease (LCDD) is a non‐amyloid monoclonal immunoglobulin light chain deposition disorder. It is usually secondary to lymphoproliferative diseases, such as multiple myeloma, B‐cell lymphoma, and some secondary to autoimmune diseases like Sjögren syndrome (SS). A small number of cases are idiopathic [1]. The kidney is the most frequently affected organ in LCDD, with about 20% of patients needing dialysis due to renal failure [2]. Pulmonary involvement, known as pulmonary light chain deposition disease (PLCDD), is relatively uncommon. Because of the rarity of PLCDD and diagnostic difficulties, there are few reports of PLCDD cases, especially those associated with SS, both in China and globally. This study presents a case of PLCDD associated with SS admitted to our hospital and reviews the relevant literature.
LCDD is a monoclonal immunoglobulin light chain deposition disease, often secondary to lymphoproliferative diseases such as multiple myeloma, B‐cell lymphoma, some secondary to autoimmune diseases such as Sjogren's syndrome, and a few cases are idiopathic.
2. Case Report
A 42‐year‐old female patient was admitted to our hospital on 12 March 2021, with a 28‐month history of intermittent cough and haemoptysis, which had worsened in the past 3 days. The symptoms started in November 2018 after a cold, with cough and bloody sputum. A shadow in the right lung middle lobe and multiple cystic changes were detected. A local hospital performed a right lung lobectomy and diagnosed it as ‘chronic inflammatory granuloma’. After the operation, the patient still had intermittent cough and blood in sputum, and the symptoms were sometimes mild and sometimes severe. In June 2019, the patient went to the doctor due to the aggravation of symptoms again. The chest CT examination revealed multiple cystic lesions in both lungs, a nodule was visible in the upper lobe of the right lung, and the anti‐SSA antibody (+++) and anti‐RO52 antibody IgG type (+++) were positive. Dry mouth, frequent water intake, no skin, muscle, and joint discomfort, Schirmer test (+), ophthalmic consultation considered dry eye, ultrasound of bilateral parotid gland and submandibular gland found low echo, 2002 American–European Consensus Group classification criteria for Sjögren's syndrome (pSS), diagnosed as Sjögren's syndrome, given hydroxychloroquine sulphate tablets. By April 2020, her daily regimen included 30 mg prednisone acetate, 0.5 g Mycophenolate mofetil, and 0.2 g hydroxychloroquine. The prednisone acetate dosage was gradually reduced. In July 2020, a pathology consultation at another hospital suggested Wegener's granulomatosis, leading to the discontinuation of Mycophenolate mofetil and the start of cyclophosphamide with a cumulative dose of 2.4 g. After the above treatment, the patient's symptoms still showed no significant changes, including cough and blood in intermittent sputum, and his symptoms of dry mouth and dry eyes were alleviated. The nodules of the upper lobe of the left lung gradually appeared, the double upper pulmonary nodules gradually increased, and the left pleural effusion appeared in the course of the disease. In October 2020, the dose of prednisone acetate was adjusted to 5 mg once daily and cyclophosphamide was discontinued. She was also treated with voriconazole 200 mg twice a day due to suspected pulmonary aspergillosis. In February 2021, there was no obvious cause of haemoptysis chest pain. After bronchial artery embolisation, she still had intermittent cough and haemoptysis and was admitted for further diagnosis.
On admission, her vital signs were normal. There was no superficial lymph node enlargement. Right upper lung percussion was turbid, with clear respiratory sounds and no rales. Cardio‐abdominal regions showed no abnormalities. Laboratory tests showed a haemoglobin level of 111 g/L, a white blood cell count of 2.76 × 109/L, and a neutrophil count of 1.48 × 109/L. The autoantibody profile had ANA1:320, anti‐SSA (++++), Ro52 (++++), and other results were negative. Other tests were normal.
A chest CT on 16 March 2021, showed a mass in the right lung upper lobe with segregated shadows, calcification, and ring‐shaped enhancement. Irregular nodular solid‐density shadows in cystic lesions in both upper lobes showed the crescent sign, with the capsule wall related to blood vessels (Figure 1). A lung puncture biopsy on 25 March 2021, revealed eosinophilic amorphous material in lung tissue and blood vessel walls with multinucleated giant cell reactions on haematoxylin and eosin stain. There was increased plasma cell infiltration in peripheral lung tissue (Figure 2A), and the deposits were Congo red stain negative (Figure 2B,C), leading to the diagnosis of PLCDD. Serum immunofixation electrophoresis, urine‐free light chain determination, and urine peripheral protein qualification were normal. PET/CT showed cystic density shadows in the right upper lobe, multiple thin‐walled cysts in both lungs, and multiple nodular shadows with low‐level FDG uptake, consistent with light chain deposition disease (Figure 3).
FIGURE 1.
High‐resolution computed tomography (CT) scan. (A) A significant mass in the upper lobe of the right lung was observed in CT scans. (B, C) Multiple capsule cavities with pulmonary nodules were demonstrated. (D) Blood vessels were found in the wall of the capsule.
FIGURE 2.
Histological features of pulmonary light chain deposition disease. (A) The lung tissue and part of the blood vessel wall deposits appear as an eosinophilic amorphous material surrounded by a multinucleated giant cell reaction on haematoxylin and eosin stain. (B, C) The deposits do not exhibit apple‐green birefringence when stained with Congo red.
FIGURE 3.
PET‐CT shows low‐level FDG uptake (SUV max ≤ 2.5).
The patient was diagnosed with pulmonary light chain deposition with SS. The recommended treatment was oral methylprednisolone 40 mg once a day and cyclophosphamide 100 mg every other day. However, she did not follow this plan. Currently, she takes oral glucocorticoids and intermittent bortezomib infusion. After 25 months of follow‐up, she still has coughing and intermittent sputum with blood, but no massive haemoptysis, and chest CT shows no significant changes.
The terms ‘pulmonary light chain deposition disease’ and ‘Sjögren syndrome’ were searched in multiple databases until 30 April 2024. Fifteen articles were retrieved, and after removing incomplete and duplicate cases, 10 papers involving [5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21] 22 patients were analysed (Table 1). There were 4 males and 18 females, aged 33–77 years (mean 52.5 ± 11.4 years). Among 16 patients with detailed symptom descriptions, symptoms included dyspnea (9/16), cough (4/16), chest pain (1/16), and haemoptysis (1/16). 31% (5/16) were asymptomatic but had abnormal chest CT. Chest CT showed nodules (15/16) and multiple cystic lesions (15/16) as common manifestations. Of 22 patients, 9 had blood or urine M‐protein testing, with 50% positive. Positive cases included IgG λ, IgG Κ, and IgM Κ. Among 4 positive M‐protein patients, 2 had hematologic diseases, while 4 negative ones had no such diseases. Seven patients did not receive proper treatment, 1 had unavailable information, and 14 were treated with glucocorticoids, immunosuppressants, chemotherapy, or targeted therapy. Follow‐up ranged from 6 to 120 months. Four patients had chest imaging progression, 2 were lost to follow‐up, 1 had unavailable information, and 15 had stable lung lesions.
TABLE 1.
Summary of clinical characteristics in 22 patients with PLCDD with Sjögren syndrome.
| Reference | N | Sex (M/F) | Respiratory symptoms at presentation | Chest CT | M protein | Underlying disease | Treatment | Outcome | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Nodule | Cysts | Cyst wall relationship to vessel | ||||||||
| Aluri et al. [12] | 1 | −/1 | Shortness of breath | 1 | 1 | NA | 1/1 | None | GC + HCQ + MMF | Stable |
| Ussavarungsi et al. [13] | 1 | −/1 | Shortness of breath | 1 | 1 | NA | NA | None | None | Stable |
| Arrossi et al. [7] | 2 | −/2 |
1/2 None 1/2 Chest pain |
2 | 1 | NA | 1/2 | 1/2 MZL |
1/2 GC + RTX 1/2 MTX |
2/2 stable |
| Sheard et al. [6] | 2 | 1/1 |
2/2 Shortness of breath 1/2 Cough |
2 | 2 | 2 | NA | None |
1/2 GC 1/2 CsA + MMF |
1/2 stable 1/2 progressed |
| Xiao‐xiao et al. [14] | 4 | 1/3 |
2/4 None 2/4 Shortness of breath 2/4 cough 1/4 haemoptysis |
4 | 4 | NA | 2/4 | 1/4 MALT lymphoma |
1/4 GC 1/4 GC + CTX 1/4 Chemotherapy treatment 1/4 NA |
2/4 stable 2/4 censor |
| Todhe et al. [15] | 1 | 1/0 | Shortness of breath, cough | 1 | 1 | NA | NA | MALT lymphoma | Chemotherapy treatment | Progressed |
| Wei et al. [16] | 3 | −/3 | 3/3 None | 3 | 3 | 3 | 0/1 | None | 3/3 GC + HCQ |
1/3 stable 2/3 progressed |
| Baqir et al. [5, 17] | 6 | −/6 | # | 6 | 6 | NA | NA | 4/6 MALT lymphoma |
5/6 None 1/6 Melphalan + GC |
6/6 stable |
| Ahluwalia et al. [18, 19] | 1 | −/1 | Shortness of breath | NA | 1 | NA | NA | MALT lymphoma | RTX | NA |
| Steward et al. [20, 21] | 1 | 1/0 | Shortness of breath | 1 | 1 | NA | 0/1 | None | None | Stable |
Abbreviations: #, the information provided does not clarify respiratory symptoms of each patient separately; CsA, cyclosporine A; CTX, cyclophosphamide; F, female; GC, glucocorticoid; HCQ, hydroxychloroquine; M, male; MALT, mucosa‐associated lymphoid tissue; MMF, Mycophenolate Mofetil; MTX, methotrexate; MZL, marginal zone lymphoma; NA, not available; RTX, rituximab; TCD, thalidomide + cyclophosphamide + dexamethasone.
3. Discussion
LCDD is a monoclonal immunoglobulin light chain deposition disease, often secondary to lymphoid tissue proliferative diseases or autoimmune diseases like SS, with some idiopathic cases [1]. Renal involvement causes haematuria, proteinuria, or renal insufficiency, and other organs can be affected, with lung involvement being rare [3]. The first PLCDD case was reported in 1988 [4]. PLCDD with SS is rare, more common in middle‐aged women. The case reported in this study was a middle‐aged woman.
PLCDD's respiratory symptoms are non‐specific, including dry cough, dyspnea, and chest pain, and some may have intermittent haemoptysis. Some patients may be asymptomatic. The patient in our study presented with recurrent cough and haemoptysis, with once massive haemoptysis during the disease. The cause of haemoptysis is unclear but is considered to be related to eosinophilic deposition in alveolar and vascular basement membranes [5]. Foreign scholars summarised the imaging manifestations of 9 cases of PLCDD with different aetiologies. All patients exhibited multiple cystic lesions visible on chest CT, with the cyst wall closely associated with blood vessels. In 7 patients, blood vessels were observed on the cyst wall, and some blood vessels were found to penetrate within the cyst wall. Additionally, chest CT scans revealed lung nodules in 8 out of 9 patients, with most having 2 or more nodules [6]. The imaging findings of patients with PLCDD combined with SS in this study were consistent with the aforementioned characteristics, as supported by existing literature. The presence of multiple cystic lesions and multiple nodules on CT scans is a common manifestation of the disease. Therefore, the presence of these features in imaging should raise suspicion for PLCDD. It is important to recognise that while these imaging features are common in PLCDD, they are not specific to the disease. The other cystic lung diseases that should be distinguished are pulmonary Langerhans cell hyperplasia, pulmonary lymphangiomyomatosis, and lymphocytic interstitial pneumonia.
LCDD has nodular and diffuse histological types [3]. The nodular type has extracellular nodular deposits with multinucleated giant cells and plasma cell infiltration, often associated with autoimmune diseases [3, 6]. The diffuse type has eosinophilic deposition in basement membranes and is common in multisystemic involvement. It is essential to differentiate PLCDD from pulmonary amyloidosis. While both show unstructured material stained with haematoxylin–eosin in lung histopathologies, LCDD's light chains do not form a β‐fold structure, and Congo red stain is negative, unlike amyloidosis, where the deposited material forms a reverse parallel β‐fold and Congo red stain is positive.
Patients with positive M‐protein in blood or urine are more likely to have haematological diseases and extrapulmonary organ involvement [7]. In our case, M‐protein and PET/CT were normal, and there was no extrapulmonary organ involvement.
There is no standardised treatment for PLCDD with SS. Treatment depends on SS disease activity and extrapulmonary organ involvement, using glucocorticoids, immunosuppressants, chemotherapy, or targeted therapy. For patients in end‐stage PLCDD, lung transplantation may be a viable option [8, 9]. Some reports have mentioned haematopoietic stem cell transplantation as a treatment for PLCDD combined with macroglobulinaemia and plasma cell disease [10, 11], but long‐term efficacy needs confirmation. PLCDD is generally considered a slow‐progressing disease [6], with the nodular type having a more favourable prognosis than the diffuse type [3]. Although our literature review does not provide further differentiation of patients with PLCDD combined with SS by pathologic subtype, the overall prognosis appears to be positive. Cases without concurrent hematologic disease or extrapulmonary organ involvement reviewed above did not show significant progression during follow‐up, even without specific treatment.
In conclusion, PLCDD is rare, and its combination with SS is even rarer, prone to misdiagnosis. For SS patients with specific chest imaging features, PLCDD should be considered. Histopathologic biopsy is the gold standard for diagnosis. Blood or urine M‐protein testing is recommended for confirmed cases. There is no standardised treatment, and the long‐term benefits of some treatment options are unknown. The overall prognosis is favourable, but more cases are needed for confirmation.
Author Contributions
Prof. Tiemei Zhao conceived the project and edited the final manuscript. Dr. Kan Zhang conducted the investigation process, data collection, and manuscript writing. Dr. Jie Gao and Dr. Xiaofei Liu contributed to the cases. Dr. Dingyun Song contributed to the revisions of the text. All the authors have read and approved the final manuscript and agreed to be accountable for all aspects of the work.
Ethics Statement
The authors declare that appropriate written informed consent was obtained for the publication of this manuscript and accompanying images. Permission was granted by the ethics committee of the Chinese People's Liberation Army General Hospital (309202103161000).
Conflicts of Interest
The authors declare no conflicts of interest.
Associate Editor: Arata Azuma
Kan Zhang and Jie Gao should be considered as co‐first authors.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.