Multi-organ Involvement in Refractory IgG4-related Disease

Abstract

IgG4-related disease (IRD) is a type of lymphoplasmacytic disease with multi-organ involvement. It is characterized by elevation of serum IgG4 levels and tissue infiltration of IgG4-positive plasma cells. Autoimmune pancreatitis, sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis and lymphadenopathy make up its main clinical manifestations, but almost any organ can be involved. The present difficult case was encountered in our hospital. The gentleman involved was middle-aged male of Indian heritage. He presented with a constellation of interstitial pneumonitis, periaortitis, pansinusitis, nephritis, prostatitis, dacryoadenitis and otitis media. Unexpectedly, multiple auto-antibody serologies measured at different intervals including serum IgG4 were all negative. This complex presentation was eventually diagnosed as IRD, namely through the histopathological findings demonstrating evidence of IgG4+ cells on immunohistochemical staining. The patient was non-responsive to high-dose steroid therapy and failed to improve on cyclophosphamide treatment also. Eventually, better disease control was achieved with the monoclonal anti-CD20 antibody rituximab. To the best of our knowledge, this is the first case report of a patient presenting with 7 different organ manifestations in a biopsy-confirmed IRD. Serial CT and PET/CT scans were used throughout this case to monitor the degree of organ involvement, disease remission and response to treatment.

Zusammenfassung

Die IgG4-assoziierten Erkrankungen sind eine Form der lymphoplasmozytischen Erkrankungen mit Multiorganbeteiligung. Sie sind durch einen erhöhten Serum IgG4-Spiegel sowie durch eine Gewebsinfiltration mit IgG4-positiven Plasmazellen gekennzeichnet. Autoimmunpankreatitis, sklerosierende Cholangitis, sklerosierende Sialadenitis, retroperitoneale Fibrose und eine Lymphadenopathie sind die häufigsten klinischen Manifestationen, es kann jedoch jedes Organ befallen werden. Dieser komplexe Fall berichtet über einen Patienten mittleren Alters, indischer Herkunft. Im klinischen Verlauf zeigte sich eine Konstellation von interstitieller Pneumonitis, Periaortitis, Pansinusitis, Nephritis, Prostatitis, Dacryoadenitis und Otitis media. Multiple Autoantikörper sowie die IgG4-Serumkonzentration blieben unauffällig. Diese komplexe Multiorganerkrankung wurde letztendlich histopathologisch sowie immunhistochemisch, mit der Evidenz von IgG4+Zellen diagnostiziert. Der Patient zeigte unerfreulicher weise kein Ansprechen auf Kortikosteroide und Cyclophosphamid. Eine Remission konnte letztendlich mit dem monoklonalen anti-CD20 Antikörper Rituximab erreicht werden. Zur Darstellung der Organbeteiligungen sowie dem Ansprechen auf die Therapie wurden serielle CT und PET/CT Untersuchungen durchgeführt. Nach unserem Wissensstand ist dies der erste Fall einer Biopsie gesicherten IgG4-assoziierten Erkrankung, bei der 7 Organmanifestationen beobachtet werden konnten.

Key words

IgG4-related disease - Multi-organ involvement - Refractory disease - Rituximab - IRD

Schlüsselwörter

IgG4-assoziierte Erkrankung - Multiorganbeteiligung - Refraktäre Erkrankung - Rituximab - IGAE

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