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Inicio Gastroenterología y Hepatología (English Edition) Pulmonary aspergillosis in a Crohn's disease patient receiving adalimumab and st...
Información de la revista
Vol. 42. Núm. 6.
Páginas 387-388 (junio - julio 2019)
Vol. 42. Núm. 6.
Páginas 387-388 (junio - julio 2019)
Scientific letter
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Pulmonary aspergillosis in a Crohn's disease patient receiving adalimumab and steroid therapy
Paciente con enfermedad de Crohn en tratamiento con adalimumab y esteroides que desarrolla aspergilosis pulmonar
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Isabel Ferrer Bradley
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, Nuria Maroto Arce, María Mora Escrig, Joaquín Hinojosa del Val
Unidad de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Hospital de Manises, Manises, Valencia, Spain
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We present the case of a 41-year-old male patient diagnosed with ileocolic Crohn's disease (CD) in 1999 (A2 L3 B1+p), with ileocaecal resection in 2006, on treatment with mercaptopurine for prevention of recurrence. He subsequently developed a complex perianal fistula, which was initially treated with infliximab before switching to adalimumab in 2013 due to a sensitivity reaction, with good response and withdrawal of mercaptopurine. In 2016, adalimumab (80–80–80mg/week) was reintroduced due to loss of response with perianal and luminal activity. Due to the patient's lack of improvement, steroids were added (1mg/kg=80mg). One month after starting the treatment, the patient reported a three-day history of weight loss, cough and expectoration. The chest X-ray revealed several cavitated nodular images in both lung fields consistent with pulmonary tuberculosis. The study was broadened to include CT scan, blood panel, Mantoux test and bronchoscopy. The chest CT scan (Fig. 1) showed bilateral cavitated nodular images, the Mantoux test was negative and the blood tests only revealed a slight increase in CRP (15mg/l) and fibrinogen (520mg/dl). The bronchoscopy was normal, samples were taken for culture and bronchoalveolar lavage was performed. The microbiological study for mycobacteria was negative (AAFB and culture in Löwenstein medium). The microbiological study was broadened and multiple Aspergillus spp. colonies were isolated. Adalimumab was withdrawn and treatment with intravenous voriconazole, imipenem and cilastatin was started. After three months of treatment, the patient had no pulmonary or intestinal symptoms, together with radiological improvement, so adalimumab was reintroduced.

Figure 1.

Lung CT scan.

(0.06MB).

Patients with inflammatory bowel disease (IBD) are particularly susceptible to opportunistic infections thanks to the use of immunosuppressants, particularly if several are used in combination (steroids, immunomodulators and biologicals). The overall risk is minimal, particularly in monotherapy, and steroids are most associated with high risk and onset of infection. In our case, the addition of corticosteroids probably played a key role. Age is an independent factor, with older patients at greater risk. As such, the risk/benefit ratio of combination therapy should be carefully assessed in these patients, together with closer monitoring. Fungal infections are rare, but morbidity and mortality is high (50%).1 Clinical suspicion is vital in order to make an early diagnosis and to administer the appropriate treatment to prevent complications. Aspergillus fumigatus is the most common species to cause infection (90%). There are very few published cases of mycosis associated with treatment with adalimumab in patients with IBD.2,3 Invasive aspergillosis primarily affects the lungs and the symptoms are nonspecific (cough, chest pain and dyspnoea). It is difficult to diagnose as it requires the combination of consistent radiological findings and mycological criteria (histological evidence of invasive hyphae or positive culture of a normally sterile medium such as pleural fluid are consistent with invasive fungal disease). In this case study, granulomatous CT images were observed that are not specific to mycosis, with multiple negative microbiological studies. As a result, a pleural fluid culture was performed, which was positive, thereby confirming the diagnosis. In clinical practice, antifungal treatment is started early, even before a confirmatory positive culture, because of the risk of not treating it and its complications.4 The drug of choice is voriconazole. Combination therapy with caspofungin is used in patients with serious conditions or a poor prognosis. The optimal duration of treatment is unknown. For pulmonary aspergillosis, at least 6–12 weeks are generally recommended. In immunosuppressed patients, treatment should continue for the duration of immunosuppression and until resolution of the lesions.5 The optimal time to re-introduce biological therapy has also not been definitively established and will depend on the patient's characteristics, but in any case it should not be restarted until the lesions have resolved or improved. The European Crohn's and Colitis Organisation (ECCO) guidelines provide no guidance in this respect.1 Experience with lung transplants reported by pulmonologists suggests that biological therapy could be reintroduced once antifungal treatment has been initiated.

In conclusion, patients with IBD treated with several immunosuppressants (steroids, biologicals or immunomodulators) are more susceptible to infection.

Invasive fungal infections are becoming increasingly common in immunocompromised patients (HIV, cancer patients, transplant patients, IBD, older patients and patients on steroids).

Invasive aspergillosis is complicated to diagnose. It requires the combination of clinical symptoms, consistent radiological findings and mycological criteria (histological evidence of invasive hyphae or positive culture).

Voriconazole is the treatment of choice for aspergillosis. Duration of treatment has not been well defined as it depends on the extent of the disease and on the patient's immune system.

At least 6–12 weeks of treatment are generally recommended. In immunosuppressed patients, treatment should continue for the duration of immunosuppression and until resolution of the lesions.

References
[1]
J.F. Rahier, F. Magro, C. Abreu, A. Armuzzi, S. Ben-Horin, Y. Chowers, et al.
Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease.
J Crohns Colitis, 8 (2014), pp. 443-468
[2]
M. Salavert, G. Bastida, J. Pemán, P. Nos.
Opportunistic co-infection in a patient with Crohn's disease during infliximab (anti-TNFalpha) therapy.
Rev Iberoam Micol, 26 (2009), pp. 213-217
[3]
D. Marti Aguado, M.P. Ballester, M.M. Bosca Watts.
Invasive pulmonary aspergilosis in an immunocompromised patient with severe ulcerative colitis.
Rev Esp Enferm Dig, 109 (2017), pp. 316-317
[4]
T.J. Walsh, E.J. Anaissie, D.W. Denning, R. Herbrecht, D.P. Kontoyiannis, K.A. Marr, et al.
Treatment of aspergillosis: clinical practice guidelines of the Infectious Disease Society of America.
Clin Infect Dis, 46 (2008), pp. 327-360
[5]
M. Dave, T. Purohit, R. Razonable, E.V. Loftus Jr..
Opportunistic infections due to inflammatory bowel disease therapy.
Inflamm Bowel Dis, 20 (2014), pp. 196-212

Please cite this article as: Ferrer Bradley I, Maroto Arce N, Mora Escrig M, Hinojosa del Val J. Paciente con enfermedad de Crohn en tratamiento con adalimumab y esteroides que desarrolla aspergilosis pulmonar. Gastroenterol Hepatol. 2019;42:387–388.

Copyright © 2018. Elsevier España, S.L.U.. All rights reserved
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