Case of summer-type hypersensitivity pneumonitis complicated with IgA nephropathy

Abstract

Association between pulmonary disease and IgA nephropathy (IgAN) has been previously reported. However, no association has been reported between hypersensitivity pneumonitis (HP) and IgAN. Here, we report about a patient with no particular medical history, who experienced worsening dyspnoea in the course of 1 month, with ground-glass opacity on chest CT and no improvement after antibiotic therapy. The patient was diagnosed as having HP based on the history of antigen exposure, detection of Trichosporon asahii-specific antibodies and bronchoscopy findings. Concomitantly, findings of renal biopsy revealed the IgAN diagnosis. The patient underwent corticosteroid therapy, with good outcomes for both HP and IgAN. This is the first report in the literature to describe summer-type HP complicated with IgAN.

Background

Hypersensitivity pneumonitis (HP) is an allergic disease classified as a type Ⅲ and IV hypersensitivity, caused by repeated inhalation of antigens, which predominantly affects the bronchioles.¹IgA nephropathy (IgAN) is a glomerular disease, characterised by IgA deposition in the glomerular mesangial area, commonly manifested by haematuria and proteinuria.² It is triggered by upper respiratory tract infections and is associated with type Ⅲ hypersensitivity.² Association between pulmonary diseases and IgAN has been suggested in several cases.^3–9 However, no reports of HP-associated IgAN have been published to date. Here, we present a case of HP complicated with IgAN.

Case presentation

A 62-year-old male patient with past smoking history, but no other significant past medical history, presented with persistent cough for 1 month, dyspnoea and low-grade fever. He was a construction worker with possible asbestos exposure and did not take any medicine or dietary supplements regularly. He undertook annual health check-up in April every year and had no history of urine abnormalities pointed out. He was seen at two other hospitals, where antibiotics (azithromycin and levofloxacin) were prescribed but did not lead to symptom improvement. He was then referred to our department in September and was immediately hospitalised.

Investigations

On admission, the patient was afebrile and had tachypnoea (30 breaths/min) with oxygen saturation of 91% on ambient air. He had diffused fine crackles on auscultation, normal heart sound without murmur and had no leg oedema. Chest radiography and chest CT showed diffuse ground-glass opacity (GGO), predominantly in the central lung field (figure 1). Laboratory data are displayed in table 1. Arterial blood gas analysis showed a pH 7.46, PCO₂ of 33.8 mm Hg, PO₂ of 68.9 mm Hg and HCO₃ ⁻ levels of 23.7 mEq/L. Complete blood counts showed that both total differential white blood cell counts were normal. Biochemical examination revealed normal levels of serum creatinine (0.84 mg/dL), decreased levels of total protein (6.4 g/dL) and serum albumin (2.9 g/dL) and increased levels of blood urea nitrogen (23.8 mg/dL), C reactive protein (3.88 mg/dL), KL-6 (5468.7 U/mL) and surfactant protein D (201.7 ng/mL). Other biochemical parameters were within the normal range. Antinuclear antibody test was positive (1:80), with no elevation of other specific autoantibodies. The urine protein to creatinine ratio was 1172.9 mg/gCr, urine albumin to creatinine ratio was 501.1 mg/gCr, and urine sedimentation test showed a red blood cell count of 100/HPF (table 1).

Figure 1.

Patient’s chest radiography (A) and CT (B) on admission revealing diffuse ground-glass opacities, predominantly in central lung field. After corticosteroid therapy, the chest radiography outcomes improved over time.

Table 1.

Laboratory findings

		(Normal range)
Blood test
White cell count (109/L)	6.6	(3.3–8.6)
Differential count (%)
Neutrophils	66.7	(41.7–73.7)
Lymphocytes	19.2	(18.4–44.8)
Monocytes	5.3	(4.6–12.3)
Eosinophils	8.0	(0.7–8.1)
Haemoglobin (g/L)	137	(13.7–16.8)
Haematocrit (%)	40.3	(40.7–50.1)
Platelet count (109/L)	158	(158–348)
AST (U/L)	53	(13–30)
ALT (U/L)	22	(10–42)
LDH (U/L)	434	(124–222)
Total bilirubin (mg/dL)	0.9	(0.4–1.5)
Total protein (g/dL)	6.4	(6.6–8.1)
Albumin (g/dL)	2.9	(4.1–5.1)
Blood urea nitrogen (mg/dL)	23.8	(8.0–20.0)
Creatinine (mg/dL)	0.8	(0.85–1.07)
Na (mEq/L)	138	(138–145)
K (mEq/L)	3.9	(3.6–4.8)
Cl (mEq/L)	109	(101–108)
CRP (mg/dL)	3.88	(0–0.14)
KL-6 (U/mL)	5469	(105.3–401.2)
Surfactant protein D (mg/dL)	201.7	(<110)
Brain natriuretic peptide (pg/mL)	627	(<18.4)
Antinuclear antibody	1:80	(<40)
Anti-Trichosporon asahii antibody (CAI)	3.09	(<0.15)
Rheumatoid factor (ng/mL)	15	(≤15)
MPO-ANCA (U/mL)	<1.0	(<3.5)
PR3-ANCA (U/mL)	1.3	(<3.5)
Anti-ARS antibody	negative	(negative)
Anti-MDA5 antibody	negative	(negative)
Anti-GBM antibody	negative	(negative)
Arterial blood gas
pH	7.464	(7.35–7.45)
PaO2 (mm Hg)	59.5	(80–100)
PaCO2 (mm Hg)	33.8	(35–45)
HCO3 − (mmol/L)	23.7	(22–28)
Lactate (mmol/L)	1.22	(0.5–2.0)
Urine test
Urine sedimentation test
Red blood cell (/HPF)	>100	(<5)
White blood cell (/HPF)	1–4	(<5)
Hyaline cast (/HPF)	<1	(<1)
Granular casts (/HPF)	<1	(<1)
Urine protein to creatinine ratio (mg/gCR)	1173	(<27)
BALF analysis
Total cell counts (/mL)	730 000
Histiocytes (%)	9.5
Lymphocytes (%)	75.9
Neutrophils (%)	11.8
Eosinophils (%)	2.8
CD4/CD8 ratio	0.58

ANCA, antineutrophil cytoplasmic antibodies; ALT, alanine aminotransferase; ARS, aminoacyl-tRNA synthetase; AST, aspartate transaminase; BALF, bronchoalveolar lavage fluid; CRP, C reactive protein; GBM, glioblastoma multiforme; KL-6, Kerbs von Lungren 6 antigen; LDH, lactate dehydrogenase; MDA5, melanoma differentiation-associate gene; MPO, myeloperoxidase; PR3, proteinase 3.

Bronchoscopy was performed on the day of admission, and bronchoalveolar lavage (BAL) examination showed remarkably elevated cell density, with increased lymphocyte proportion (75.9% of lymphocytes, 9.5% of histiocytes, 11.8% of neutrophils and 2.8% of eosinophils) and decreased CD4/CD8 ratio (0.58). BAL fluid (BALF) showed a colourless and transparent aspect. Transbronchial lung biopsy was performed, but the specimen was not sufficient for definitive pathological diagnosis. BALF culture was negative for pathogenic microorganisms. Later, serum antibodies to Trichosporon asahii turned out to be highly positive (corrected absorbance index=3.09). For definitive diagnosis of proteinuria and hypoalbuminemia, renal biopsy was performed on day 15 and revealed mesangial proliferation inH&E stainingand IgA deposition in the mesangium in immunofluorescence, indicative of IgAN (figure 2). The final diagnosis was summer-type hypersensitive pneumonitis complicated with IgAN.

Figure 2.

Patient’s renal biopsy. H&E staining (A) shows mesangial proliferation and mesangial matrix expansion, with no findings of endocapillary proliferation, inflammatory cell infiltration or crescent formation. Immunofluorescence (B) shows IgA deposition in the mesangial area. IgAN was diagnosed from these findings, and other renal diseases, such as Goodpasture syndrome or vasculitis, were ruled out. IgAN,IgA nephropathy.

Treatment

The patient underwent intravenous therapy with 1000 mg of methylprednisolone for 3 days, followed by 60 mg/day of oral prednisolone (PSL) for the next 18 days. His symptoms, laboratory exams, radiological findings and proteinuria improved with time (figure 3). As the patient mentioned the use of air conditioning, which had not been sanitised for the last 15 years, we performed an environmental assessment of his home. The air conditioning system was replaced, and the wooden floor, which was decayed (figure 4), was renovated before discharge.

Figure 3.

Patient’s clinical course. The patient was initially treated with pulse steroid therapy, followed by oral corticosteroid. KL-6 levels and urine protein to creatinine ratio (UPCR) decreased after steroid therapy. The dose of oral steroid was gradually decreased, and there was no apparent relapse to date. KL-6, Kerbs von Lungren 6 antigen; PSL, prednisolone.

Figure 4.

Patient’s house. The rainwater often leaked through the door, leading the wooden floor to decay. The floor was replaced before patient’s discharge.

Outcome and follow-up

The dose of PSL was gradually decreased, and the patient was discharged on day 52. There has been no recurrence so far, under an 8 mg dose of PSL.

Discussion

We present a case of a patient with no particular medical history who experienced worsening dyspnoea in the course of 1 month, with GGO found on chest CT and no improvement after antibiotic therapy. The patient was diagnosed with HP based on the history of antigen exposure, detection of specific antibodies to T. asahii and bronchoscopy findings (predominantly lymphocytic, with low CD4/CD8 ratio). Additionally, IgAN was diagnosed from findings of renal biopsy. He underwent corticosteroid therapy with subsequent improvement of both HP and IgAN.

Hypersensitive pneumonitis is a disease caused by type Ⅲ and IV hypersensitivity.¹ Repeated exposure to airborne antigens induces formation of immune complexes with IgA and IgG, as well as complement activation.¹⁰ One of the most common pathogens causing summer-type HP in Japan is T. asahii.¹⁰

IgAN is a glomerular disease associated with type III hypersensitivity to external antigens, and its aetiology is influenced by a combination of genetic and environmental factors. Upper respiratory tract infections are suggested to be one of the main underlying causes of the hypersensitivity reaction leading to IgAN, characterised by deposition of circulating IgA immune complexes in the glomerular mesangial area.^{2 11}

The association between pulmonary diseases and IgAN has been previously reported, including silicosis, sarcoidosis, bronchiolitis obliterans, pulmonary haemorrhage and interstitial pneumonitis.^3–9 However, to the best of our knowledge, the present case is the first report of HP complicated with IgAN.

Furthermore, IgAN and HP share a similar pathophysiology (type Ⅲ hypersensitivity), suggesting that a common antigen may trigger both HP and IgAN. Also, upper respiratory tract infection is suggested to be the underlying cause of IgAN. Taken together, respiratory tract inflammation caused by HP may trigger an immune response leading to the manifestation or worsening of IgAN.

In conclusion, we present a case of HP complicated with IgAN. Therefore, urinary markers are noteworthy in patients with HP. However, further researches are needed to strongly establish a causality between the two conditions.

Learning points.

• This case is the first report of hypersensitivity pneumonitis (HP) complicated with  IgA nephropathy.

• Associations between the two conditions rely on the findings of previous studies and common pathophysiological mechanisms.

• Urinary markers are noteworthy in HP.