Elevated serum IgG4 levels in two cases of paragonimiasis.

Paragonimiasis is a parasitic pleuropulmonary infection caused by eating raw crustaceans and wild boar meat and this infection is endemic in Asia. We herein report two cases of pulmonary P aragonimus westermani infection associated with elevated levels of serum immunoglobulin (Ig) G4 and dense infiltration of IgG4-positive plasma cells in the lung lesions. Treatment with praziquantel resolved the pulmonary lesions and decreased the serum levels of IgG4. IgG4-related disease is a systemic disease occasionally involving the lungs and leads to increased serum levels of IgG4. Our findings suggest that P. westermani infection requires a differential diagnosis from IgG4-related diseases and the serum IgG4 level may be a potentially useful marker of P. westermani infection.

Introduction

Paragonimiasis is an endemic foodborne trematode infection by Paragonimus westermani in Asia, including Japan, which results from the consumption of raw crustaceans and wild boar meat [1]. As the number of immigrants and travelers from endemic areas increase worldwide, more cases of P. westermani in non-endemic areas have also been reported. We herein report two cases of paragonimiasis with elevated serum immunoglobulin (Ig) G4 levels and the infiltration of IgG4-positive plasma cells in the pulmonary lesions. These findings suggest that paragonimiasis should therefore be included in the differential diagnosis of IgG4-related diseases.

Case Report

Case 1

A 49-year-old man without any complaints demonstrated consolidation in the right upper lobe on a chest X-ray and computed tomography (CT) imaging (Fig. 1A) and the consolidation was spontaneously resolved. Two years later, he developed hemosputum and the chest CT imaging showed a new solitary pulmonary nodule in the right middle lobe (Fig. 1B). We then performed a transbronchial biopsy of the lesion. The pathology of the lesion showed Paragonimus ova (Fig. 1D) infiltrated by IgG4-positive plasma cells (Fig. 1E and F). The tissue eosinophils were not prominent. The serum level of IgG4 was elevated (201 mg/dL; normal range: 4.8–105 mg/dL), but those of IgE was not elevated (206 U/I). The patient's history included previous consumption of raw wild boar meat and a high titer of serum IgG for P. westermani was detected by an enzyme-linked immunosorbent assay (ELISA). According to these results, the patient was diagnosed with paragonimiasis. Praziquantel treatment improved his symptoms and the pulmonary shadow resolved (Fig. 1C); 4 months after the treatment, the serum level of IgG4 decreased to within the normal range (75.6 mg/dL) (Table 1).

Figure 1

Chest computed tomography images and microscopic findings of the transbronchial biopsy specimens in Case 1. (A) Pulmonary consolidation in the right upper lobe is shown. (B) A new solitary pulmonary nodule in the right middle robe was detected 2 years later. (C) Four months after the treatment with praziquantel, the lesion was resolved. (D) Paragonimus ova (arrow) infiltrated by inflammatory cells and multinucleated giant cells (hematoxylin and eosin staining, 40×). (E) Immunohistochemistry (IHC) of CD138 indicates the infiltration of plasma cells (20×). (F) IHC of immunoglobulin (Ig) G4 shows IgG4-positive plasma cells (20×).

Table 1

Laboratory data: pretreatment and post-treatment in two patients with paragonimiasis

		Case 1		Case 2
Laboratory data	Reference range	Pretreatment	Post-treatment*	Pretreatment	Post-treatment†
		Leukocytes, μL	3500–8500	5100	4400	7400	10,900
Eosinophils, %	0–0.6	1.6	2.9	3.1	0.7
Serum IgE, U/L	<400	206	Not determined	2895	1710
Serum IgG4, U/L	4.8–105	201	75.6	374	115

*Four months after praziquantel treatment. †Eleven months after praziquantel treatment. Ig, immunoglobulin.

Case 2

A 56-year-old woman developed hemosputum. A cavitary lesion in the left upper lobe was found by chest CT imaging. Bronchoscopy did not indicate any diagnostic findings and the shadow spontaneously shrunk after 3 months. Ten months later, the CT imaging revealed a new cavitary lesion in the left lower lobe. The pathology of a transbronchial biopsy specimen from the lesion showed inflammation with an increased number of plasma cells. The tissue eosinophils were not prominent. Although Paragonimus ova were not detected in the tissue, a high titer of serum IgG for P. westermani was detected via ELISA. According to these findings and her repeated history of cooking raw boar meat, the patient was diagnosed with paragonimiasis. Elevated serum levels of IgG4 and IgE were detected (374 mg/dL and 2895 U/I) and the majority of plasma cells infiltrating the lesion were IgG4-positive. Praziquantel treatment improved the pulmonary shadow and decreased the serum level of IgG4 to 114 mg/dL 11 months after the treatment (Table 1).

Discussion

We herein describe two cases of pulmonary paragonimiasis with increased serum levels of IgG4 and infiltration of IgG4-positive plasma cells in the lesions. These cases indicated that making a differential diagnosis of pulmonary paragonimiasis and IgG4-related disease is difficult in patients with pulmonary nodules or infiltration and increased serum levels of IgG4. To the best of our knowledge, this is the first report to suggest the usefulness of serum IgG4 levels as a diagnostic and treatment marker of P. westermani infections.

Paragonimiasis is caused by eating raw or undercooked crustaceans (as a second intermediate host) or wild boar meat (as a paratenic host) [1]. The metacercariae of P. westermani penetrates the duodenum and reaches the pleural spaces and lungs via the diaphragm. As a result, various symptoms and radiological findings occur, such as abdominal pain, fever, hemosputum, pleural effusion, pulmonary nodules, and infiltrations.

IgG4-related disease is a recently recognized, novel fibroinflammatory disease which affects various organs, such as the pancreas, periorbital tissues, salivary glands, kidneys, and lungs. This disease is characterized by elevated serum IgG4 levels and tumefactive lesions with dense IgG4-positive plasma cells infiltrations [2], [3]. Because the pleuropulmonary lesions in IgG4-related disease are associated with a variety of radiologic abnormalities [4], P. westermani infections and IgG4-related disease are occasionally indistinguishable by the radiological findings alone. Without carefully noting the patients' previous histories, including eating habits, the present cases may have been diagnosed as an IgG4-related disease.

It is well known that helminth infections promote Th2 immune responses which in turn elevate both the IgE and IgG4 levels including paragonimiasis [5]. In the other helminth infections, schistosomiasis and filariasis, elevated serum IgG4 levels have also been reported. IgG4 has been considered to be a blocking antibody due to its ability to compete with IgE antibodies. The balance of immune responses in helminth parasite infections could be changed by pathophysiological conditions. For example, in silent or chronic helminth infections, predominant Th2 immune response was reported. In the present cases, the lack of eosinophilia and elevated IgG4 levels probably represent predominant Th2 immune response and chronic infectious conditions.

However, the roles of IgG4 in P. westermani infection have not yet been fully elucidated and the serum levels of IgG4 after treatment have not yet been examined. The present cases demonstrated that treatment with praziquantel improved the pulmonary lesion infiltrated with IgG4-positive plasma cells and decreased the serum levels of IgG4, thus suggesting serum IgG4 to be a potentially useful marker of P. westermani infection. However, further investigation into the precise roles of IgG4 in P. westermani infection is necessary.

Disclosure Statements

No conflict of interest declared.

Appropriate written informed consent was obtained for publication of this case report and accompanying images.