Simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy

Abstract

Background: Paradoxical inflammations during anti-TNF-α therapy are defined as adverse effects such as psoriasiform skin lesions, uveitis and sarcoidosis-like granulomas induced by immune reactions, not by infectious agents. Here, we report a very rare case of the simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy and both of which resolved spontaneously without the cessation of infliximab.

Case presentation: In September 2000, 23-year old Japanese male was diagnosed with Crohn's disease. Prednisolone in combination with mesalazine was introduced at first and succeeded for almost one year. In June 2002, since his gastrointestinal symptoms relapsed and were refractory, infliximab (IFX) therapy 5 mg/kg was introduced. In February 2011, because he had repeated arthralgia almost every intravenous IFX administration, IFX was increased to 10 mg/kg under the diagnosis of a secondary failure of IFX. In December 2012, he complained of slight dry cough and an itchy eruption on both lower limbs, and he was referred to our hospital due to the appearance of bilateral hilar lymphadenopathy on chest X-ray examination. Chest computed tomogram revealed bilateral hilar lymphadenopathy and fine reticulonodular shadows on the bilateral upper lungs. Serum calcium, angiotensin-converting enzyme and soluble interleukin 2 receptor levels were not elevated, but the titer of antinuclear antibody was considerably elevated. Mycobacterium infection was carefully excluded. Trans-bronchial lung biopsy showed non-caseating epithelioid cell granulomas compatible with sarcoidosis. The skin biopsy of the right limb was diagnosed as leukocytoclastic vasculitis. The patient was diagnosed as having a series of paradoxical inflammations during anti-TNF-α therapy. Since his paradoxical inflammations were not severe and opportunistic infections were excluded, IFX was cautiously continued for refractory Crohn's disease. Nine months later, not only his intrathoracic lesions but also his cutaneous lesions had spontaneously resolved.

Conclusion: Physicians caring for patients with anti-TNF-α therapy should know that, based on a careful exclusion of infectious agents and thoughtful assessment of the patient's possible risks and benefits, paradoxical inflammations can be resolved without the cessation of anti-TNF-α therapy.

Fig. 1

a A chart delineating the clinical course of this case. After infliximab was increased to 10 mg/kg for every 8 weeks, both sarcoidosis and leukocytoclastic vasculitis developed. b A chest X ray on admission revealed bilateral hilar lymphadenopathy. c Scattered eruption on the right thigh on admission. d A Chest CT scan on admission revealed bilateral hilar lymphadenopathy and fine reticulo-nodular shadows in the peri-bronchovascular region of the bilateral upper lobes (upper panel) and positron emission tomography (FDG-PET) scan indicated increased FDG uptakes in the bilateral hilar lymph nodes (lower panel). e Nine months later, the bilateral hilar lymphadenopathy and the upper lobe reticulo-nodular shadows had spontaneously resolved

Fig. 2

a Trans-bronchial lung biopsy (TBLB) revealed non-caseating epithelioid cell granuloma with Langhans giant cells, which were compatible with sarcoidosis (HE staining, ×400). b Anti Propionibacterium acnes antibody staining was negative within this specimen. c Skin biopsy from the right thigh shown in Fig. 1d revealed leukocytoclastic vasculitis in the superficial layer of the sub-dermal portion. (HE staining, ×100). d A high-power field of Fig. 2c revealed remarkable infiltration of neutrophils around small capillaries and leukocytoclasis. (Elastica-Masson staining, ×400)