key: cord-0068154-yijo2gzl
authors: Ceciaga Elexpuru, Eneko; Arrinda Yeregui, Jose Maria; Barastay Alberdi, Estibaliz
title: IgG4-related lung disease. A case report()
date: 2021-10-05
journal: Med Clin (Engl Ed)
DOI: 10.1016/j.medcle.2020.08.013
sha: f6527590c12232d2be8f198c69a1abdaf87a9b07
doc_id: 68154
cord_uid: yijo2gzl

nan

The presence of lung lesions can be the first manifestation of multiple diseases. The aetiological range is very wide, from infectious causes to cancer disease and rheumatological diseases, among others. There are rare diseases, and their form of presentation may be atypical, making diagnosis difficult. If we add to this the fact that the onset of symptoms occurs in the middle of the SARS-CoV2 pandemic, it makes diagnosis even more difficult.

We report the case of a 51-year-old male who was admitted for a 5-day history of fever with nasal congestion, cough with purulent expectoration, without dyspnoea or chest pain. He reported asthenia with no other accompanying symptoms. A chest X-ray showed several bilateral nodular parenchymal consolidations suggestive of SARS-CoV-2 disease; so antiviral treatment with lopinavir-ritonavir and hydroxychloroquine was initiated with the patient's consent, even though the PCR results were negative for SARS-CoV-2. Given the lack of clinical and radiological improvement, a chest CT scan was performed, which reported the presence of multiple nodular images and lung masses, some with cavitation. Septic emboli were suggested as a first possibility, although the likelihood of tumour lesions could not be ruled out (Fig. 1 ). The Alberdi E. Enfermedad relacionada con IgG4 de afectación pulmonar. A propósito de un caso. Med Clin (Barc). 2020. https://doi.org/10.1016/j.medcli.2020.08.009 antiviral treatment was discontinued and a laboratory, microbiological and pathological study was started.

Laboratory tests showed thrombocytosis (593,000/l), leukocytosis (13,550/l) with neutrophilia, elevated C-reactive protein (195.8 mg/l) with normal procalcitonin, high d-dimer (1520 ng/ml) and ferritin (887 ng/ml) levels, cANCA positive (positive for proteinase 3, negative for myeloperoxidase), elevated immunoglobulin (Ig) G subclass 4 (154 mg/dl) and IgE (246 kUA/l). The cultures of the samples obtained by core-needle biopsy of the lung lesions were negative for bacteria, fungi and mycobacteria. In the anatomical pathology study, the presence of lymphocytes, plasma cells, fusiform histiocytes, some giant cells and isolated eosinophils without evidence of polymorphonuclear cells or foci of necrosis were described. The methenamine silver technique detected foci of obliterative vasculopathy. With immunohistochemistry, spindle cells expressed CD-68 and cytoplasmic lysozyme, and plasma cells showed diffuse IgG deposition and many of them had IgG4 (up to 60 IgG4 plasma cells per high-power field). All of these findings corresponded to IgG4-related lung disease.

IgG4-related disease is the name given in the previous decade to a clinicopathological entity characterized by swollen lesions, a dense lymphoplasmacytic infiltrate with abundant IgG4-positive plasma cells, storiform fibrosis and, frequently, elevated serum levels of IgG4. The prevalence of the disease is estimated to be 2.63-10.2 cases per million inhabitants in Japan. It is usually diagnosed between the sixth and seventh decades of life and predominantly in males. The most affected organs are usually the pancreas, salivary glands and lymph nodes, but renal, aortic, retroperitoneal, meningeal, prostatic and pulmonary involvement have also been described. 1 In the latter organ involvement, symptoms are usually non-specific, such as cough, dyspnoea, fever or chest pain. Sometimes there may be no symptoms at all. 2 The radiological pattern of presentation can be remarkably diverse: localized parenchymal involvement, diffuse parenchymal involvement, presence of lymphadenopathy, diffuse interstitial pattern, bronchial thickening and pulmonary nodules, as in our case. 3 In terms of laboratory tests, elevated serum levels of total IgG (61% > 1800 mg/dl), IgG4 (84% > 135 mg/dl) and IgE (58% > 360 mg/dl) stand out. It may even be positive for antineutrophil cytoplasmic antibodies. 4 Histopathological findings include a diffuse lymphoplasmacytic infiltrate, vascular obliteration and fibrosis with occasional eosinophils and the presence of abundant IgG4-positive plasma cells.

The differential diagnosis with other diseases is very broad and varied: infectious diseases such as tuberculosis, rheumatological diseases such as Sjögren's syndrome or granulomatosis with polyangiitis and malignant diseases such as lymphoma. There are international diagnostic consensus guidelines for this disease which include clinical, serological and histological criteria that are classified as definitive, probable, or insufficient evidence.

The goal of treatment is to reduce inflammation and induce remission of the disease to preserve the function of the affected organs. There is no standardised treatment for this disease, as it is based on case series, but steroid treatment is usually initiated and, depending on the response, the addition of immunosuppressants or biological agents, especially rituximab, is considered. Relapses with steroids are quite common, so a second drug is usually associated with steroids. Despite the limited evidence, several case series have observed a better clinical response in the association of prednisone + rituximab compared to steroids in monotherapy or in association with immunosuppressants (azathioprine, methotrexate, mycophenolate mofetil, cyclosporine. . . 

Enfermedad relacionada con IgG4: revisión concisa de la literatura

Clinical review of pulmonary manifestations of IgG4-related disease

Maladie à immunoglobuline G4 pulmonaire: rapport de cas et revue de littérature

Antineutrophil cytoplasmic antibody positivity in IgG4-related disease