Abstract
Acute fibrinous and organising pneumonia (AFOP) is a histopathologic variant of acute lung injury that has been associated with infection and inflammatory disorders and has been reported as a complication of lung transplantation. A retrospective chart review was performed for all patients transplanted at the University of Wisconsin Hospital and Clinics from January 1995 to December 2013 (n = 561). We identified 6 recipients whose clinical course was complicated by AFOP. All recipients were found to have AFOP on lung biopsy or at post-mortem examination, and 5 of the 6 patients suffered progressive allograft dysfunction that led to fatal outcome. Only 1 of the 6 patients stabilised with augmented immunosuppression and had subsequent improvement and stabilisation of allograft function. We could not clearly identify any specific cause of AFOP, such as drug toxicity or infection. Lung transplantation can be complicated by lung injury with an AFOP pattern on histopathologic examination of lung biopsy specimens. The presence of an AFOP pattern was associated with irreversible decline in lung function that was refractory to therapeutic interventions in 5 of our 6 cases and was associated with severe allograft dysfunction and death in these 5 individuals. AFOP should be considered as a potential diagnosis when lung transplant recipients develop progressive decline in lung function that is consistent with a clinical diagnosis of chronic lung allograft dysfunction.
Highlights
Case 1ΚΘͲLJĞĂƌͲŽůĚ ĨĞŵĂůĞ ƌĞĐĞŝǀĞĚ Ă ŚĞĂƌƚůƵŶŐ ƚƌĂŶƐƉůĂŶƚ ĨŽƌ ĐŽŶŐĞŶŝƚĂů ŚĞĂƌƚ ĚŝƐĞĂƐĞ ĂƌůLJ ƐƉƵƚƵŵ ĐƵůƚƵƌĞƐ ĚĞŵŽŶƐƚƌĂƚĞĚ 'ƌĂŵͲŶĞŐĂƟǀĞ ƌŽĚƐ ĨŽƌ ǁŚŝĐŚ ƉŝƉĞƌĂĐŝůůŝŶͲƚĂnjŽďĂĐƚĂŵ ǁĂƐ ŐŝǀĞŶ ĂŶĚ ƐŚĞ ǁĂƐ ĞdžƚƵďĂƚĞĚ ŽŶ ƚŚĞ ƐĞĐŽŶĚ ĚĂLJ ƉŽƐƚͲƚƌĂŶƐƉůĂŶƚ ĂŶĚ ĐŽŵŵĞŶĐĞĚ ĂŵďƵůĂƟŽŶ ,ŽǁĞǀĞƌ ƐŵĂůů ďŽǁĞů ĐŽŵƉůŝĐĂƟŽŶƐ ĚĞǀĞůŽƉĞĚ ĂŶĚ ƌĞƋƵŝƌĞĚ ƐƵƌŐŝĐĂů ƌĞƐĞĐƟŽŶ ĂŶĚ ƐŚĞ ĚĞǀĞůŽƉĞĚ ĚŝĂůLJƐŝƐͲĚĞƉĞŶĚĞŶƚ ĂĐƵƚĞ ƌĞŶĂů ŝŶƐƵĸĐŝĞŶĐLJ /ŶƚƵďĂƟŽŶ ĂŶĚ ŵĞĐŚĂŶŝĐĂů ǀĞŶƟůĂƟŽŶ ǁĞƌĞ ƌĞƋƵŝƌĞĚ ŽŶ ĚĂLJ ϯϬ ĂŶĚ ĐŚĞƐƚ ŝŵĂŐŝŶŐ ƐŚŽǁĞĚ ƉĞƌƐŝƐƚĞŶƚ ĚŝīƵƐĞ ŝŶĮůƚƌĂƚĞƐ ;&ŝŐƵƌĞ ϭ ĂŶĚ Ϳd ƐŚŽǁĞĚ ŵŝŶŝŵĂů ĂĐƵƚĞ ƌĞũĞĐƟŽŶ ;'ƌĂĚĞ ϭϬͿ ^ŚĞ ǁĂƐ ĞdžƚƵďĂƚĞĚ ε ĚĂLJƐ ůĂƚĞƌ ďƵƚ ƌĞƋƵŝƌĞĚ ƌĞŝŶƚƵďĂƟŽŶ ;ƉŽƐƚͲƚƌĂŶƐƉůĂŶƚ ĚĂLJ ρΘͿ ĨŽƌ ƉƌŽŐƌĞƐƐŝǀĞ ƌĞƐƉŝƌĂƚŽƌLJ ĨĂŝůƵƌĞd ďŝŽƉƐLJ ƐŚŽǁĞĚ &KW ďƵƚ ĚŝĚ ŶŽƚ ƐŚŽǁ ĂĐƵƚĞ ƌĞũĞĐƟŽŶ ;&ŝŐƵƌĞ Ϯ ĂŶĚ Ϳ ĂŶĚ ĂŶ ĞŶĚŽŵLJŽĐĂƌĚŝĂů ďŝŽƉƐLJ ǁĂƐ ŶĞŐĂƟǀĞ ĨŽƌ ĐĂƌĚŝĂĐ ƌĞũĞĐƟŽŶůĂƉĂƌŽƚŽŵLJ ĂŶĚ ƌŝŐŚƚ ŚĞŵŝĐŽůĞĐƚŽŵLJ ǁĞƌĞ ƉĞƌĨŽƌŵĞĚ ĨŽƌ ƉĞƌƐŝƐƚĞŶƚ ǀŽůǀƵůƵƐ ;ƉŽƐƚͲƚƌĂŶƐƉůĂŶƚ ĚĂLJ ϭϬϬͿ >ƵŶŐ ĨƵŶĐƟŽŶ ǁŽƌƐĞŶĞĚ ĂŶĚ Citrobacter freundii ǁĂƐ ŝƐŽůĂƚĞĚ ĨƌŽŵ ďůŽŽĚ ĐƵůƚƵƌĞƐ >͕ ĂŶĚ ƵƌŝŶĞ ĐƵůƚƵƌĞƐ ZĞƐƉŝƌĂƚŽƌLJ ƐƚĂƚƵƐ ƉƌŽŐƌĞƐƐŝǀĞůLJ ǁŽƌƐĞŶĞĚ ĂŶĚ ůŝĨĞ ƐƵƉƉŽƌƚ ǁĂƐ ǁŝƚŚĚƌĂǁŶ
Case 2ΚϭͲLJĞĂƌͲŽůĚ ĨĞŵĂůĞ ƌĞĐĞŝǀĞĚ Ă ůĞŌ ƐŝŶŐůĞ ůƵŶŐ ƚƌĂŶƐƉůĂŶƚ ĨŽƌ ĮďƌŽƟĐ ŶŽŶͲƐƉĞĐŝĮĐ ŝŶƚĞƌƐƟƟĂů ƉŶĞƵŵŽŶŝĂ ;E^/WͿƚ Ϯ ǁĞĞŬƐ ƉŽƐƚͲƚƌĂŶƐƉůĂŶƚ ƐƵƌǀĞŝůůĂŶĐĞd ƐƉĞĐŝŵĞŶƐ ƐŚŽǁĞĚ 'ƌĂĚĞ ϭϭ ĂĐƵƚĞ ƌĞũĞĐƟŽŶ ĂŶĚ d ƉĞƌĨŽƌŵĞĚ Ϯ ǁĞĞŬƐ ůĂƚĞƌ ƐŚŽǁĞĚ 'ƌĂĚĞ ϮϬ ĂĐƵƚĞ ƌĞũĞĐƟŽŶ /ŶƚƌĂǀĞŶŽƵƐ ŵĞƚŚLJůƉƌĞĚŶŝƐŽůŽŶĞ ďƵƌƐƚ ĂŶĚ ƚĂƉĞƌ ǁĂƐ ŐŝǀĞŶ ĂŶĚ ƐŚĞ ƌĞŵĂŝŶĞĚ ĂƐLJŵƉƚŽŵĂƟĐ ĂŶĚ ĐŽŶƟŶƵĞĚ ƚŽ ŝŵƉƌŽǀĞ ĐůŝŶŝĐĂůůLJ ƵŶƟů ς ǁĞĞŬƐ ƉŽƐƚͲƚƌĂŶƐƉůĂŶƚ ǁŚĞŶ ƐŚĞ ƉƌĞƐĞŶƚĞĚ ǁŝƚŚ ŝŶĐƌĞĂƐŝŶŐ ĚLJƐƉŶŽĞĂ ŽŶ ĞdžĞƌƟŽŶ ĐŽƵŐŚ ĂŶĚ ůŽǁͲŐƌĂĚĞ ĨĞǀĞƌ ƚŚĂƚ ƉƌŽŐƌĞƐƐĞĚ ƚŽ ŝŶƚƵďĂƟŽŶ ĂŶĚ ŵĞĐŚĂŶŝĐĂů ǀĞŶƟůĂƟŽŶ ^ŚĞ ǁĂƐ ƚƌĞĂƚĞĚ ǁŝƚŚ ďƌŽĂĚͲ ƐƉĞĐƚƌƵŵ ĂŶƟďĂĐƚĞƌŝĂů ĂŐĞŶƚƐ ĂŶĚ ƉƵůƐĞ ĐŽƌƟĐŽƐƚĞƌŽŝĚƐd ĚĞŵŽŶƐƚƌĂƚĞĚ ŽƌŐĂŶŝƐŝŶŐ ƉŶĞƵŵŽŶŝĂ ;KWͿ ďƵƚ ŶŽ ĂĐƵƚĞ ƌĞũĞĐƟŽŶ ĂŶĚ > ĚŝĚ ŶŽƚ ƌĞǀĞĂů ĂŶLJ ƉĂƚŚŽŐĞŶƐ ^ŚĞ ǁĂƐ ƐƵĐĐĞƐƐĨƵůůLJ ĞdžƚƵďĂƚĞĚ ĂŌĞƌ κ ĚĂLJƐ ǁĞĂŶĞĚ ƚŽ ƌŽŽŵ Ăŝƌ ĂŶĚ ĚŝƐĐŚĂƌŐĞĚ ƚŽ ŚŽŵĞ ,ŽǁĞǀĞƌ ƐƵďƐĞƋƵĞŶƚ ƐƵƌǀĞŝůůĂŶĐĞ dƐ ƐŚŽǁĞĚ ƉĞƌƐŝƐƚĞŶƚ KW ĂƐ ǁĞůů ĂƐ ĂĐƵƚĞ ƌĞũĞĐƟŽŶ ;'ƌĂĚĞ ϮϯͿ ĂŶĚ ƚŽƚĂů ůLJŵƉŚŽŝĚ ŝƌƌĂĚŝĂƟŽŶ ǁĂƐ ŝŶŝƟĂƚĞĚdŚĞ ƉĂƟĞŶƚ ǁĂƐ ƌĞĂĚŵŝƩĞĚ ς ǁĞĞŬƐ ůĂƚĞƌ ĨŽƌ ƐŚŽƌƚŶĞƐƐ ŽĨ ďƌĞĂƚŚ ĂŶĚ ŚLJƉŽdžĂĞŵŝĂ ƚŚĂƚ ƉƌŽŐƌĞƐƐĞĚ ƚŽ ƌĞƐƉŝƌĂƚŽƌLJ ĨĂŝůƵƌĞƌĞƋƵŝƌŝŶŐ ŵĞĐŚĂŶŝĐĂů ǀĞŶƟůĂƟŽŶ ĞƐƉŝƚĞ ďƌŽĂĚͲƐƉĞĐƚƌƵŵ ĂŶƟďŝŽƟĐƐ ĂŶĚ ƉƵůƐĞ ĐŽƌƟĐŽƐƚĞƌŽŝĚƐ ĚŝīƵƐĞ ƉĂƌĞŶĐŚLJŵĂů ŽƉĂĐŝƟĞƐ ;&ŝŐƵƌĞ ϭ Ϳ ƉƌŽŐƌĞƐƐŝǀĞůLJ ǁŽƌƐĞŶĞĚ ĂŶĚ ƐƵƉƉŽƌƟǀĞ ĐĂƌĞ ǁĂƐ ĞǀĞŶƚƵĂůůLJ ǁŝƚŚĚƌĂǁŶ &KW ǁĂƐ ŽďƐĞƌǀĞĚ ŝŶ ůƵŶŐ ƐƉĞĐŝŵĞŶƐ ĞdžĂŵŝŶĞĚ Ăƚ ĂƵƚŽƉƐLJ ;&ŝŐƵƌĞ Ϯ ĂŶĚ &Ϳ.
ϮςͲLJĞĂƌͲŽůĚ ŵĂŶ ƌĞĐĞŝǀĞĚ Ă ƐƵĐĐĞƐƐĨƵů ďŝůĂƚĞƌĂů ůƵŶŐ ƚƌĂŶƐƉůĂŶƚ ĨŽƌ ĞŶĚͲƐƚĂŐĞ ĐLJƐƟĐ ĮďƌŽƐŝƐ ďƵƚ ƌĞƋƵŝƌĞĚ ƐƚĞŶƚ ƉůĂĐĞŵĞŶƚ ĨŽƌ Ă ƌŝŐŚƚ ŵĂŝŶ ďƌŽŶĐŚŝĂů ƐƚĞŶŽƐŝƐ Ăƚ ƚŚĞ ĂŶĂƐƚŽŵŽƐŝƐ ƐŝƚĞ ,Ğ ĚĞǀĞůŽƉĞĚ ĐŽƵŐŚ ĚLJƐƉŶŽĞĂ ĂŶĚ ĨĞǀĞƌ ρ ŵŽŶƚŚƐ ƉŽƐƚͲƚƌĂŶƐƉůĂŶƚĂƟŽŶ ƐƉƵƚƵŵ ĐƵůƚƵƌĞƐ ĚĞŵŽŶƐƚƌĂƚĞĚ ŵƵĐŽŝĚ Pseudomonas aeruginosa ĨŽƌ ǁŚŝĐŚ ƉŝƉĞƌĂĐŝůůŝŶͲƚĂnjŽďĂĐƚĂŵ ǁĂƐ ĂĚŵŝŶŝƐƚĞƌĞĚd ƐŚŽǁĞĚ ŵŝŶŝŵĂů ĂĐƵƚĞ ƌĞũĞĐƟŽŶ ;'ƌĂĚĞ ϭϬͿ ŽƵŐŚ ĂŶĚ ĚLJƐƉŶŽĞĂ ƉĞƌƐŝƐƚĞĚ ĂŶĚ ƚŚĞ ƉĂƟĞŶƚ ƌĞƐƵŵĞĚ ƵƐĞ ŽĨ ƐƵƉƉůĞŵĞŶƚĂů ŚŽŵĞ ŽdžLJŐĞŶ ,Ğ ĂĐƵƚĞůLJ ĚĞĐŽŵƉĞŶƐĂƚĞĚ Ϯ ǁĞĞŬƐ ůĂƚĞƌ ǁŝƚŚ ĚŝīƵƐĞ ŝŶĮůƚƌĂƚĞƐ ŽŶ ƚŚŽƌĂĐŝĐ ŝŵĂŐŝŶŐ ;&ŝŐƵƌĞ ϭ Ϳ ĂŶĚ ĚĞǀĞůŽƉĞĚ ƐŚŽĐŬ ĂŶĚ ƌĞƐƉŝƌĂƚŽƌLJ ŝŶƐƵĸĐŝĞŶĐLJƌĞƋƵŝƌŝŶŐ ŝŶƚĞŶƐŝǀĞ ĐĂƌĞ ƵŶŝƚ ĂĚŵŝƐƐŝŽŶ ĂŶĚ ĂĚŵŝŶŝƐƚƌĂƟŽŶ ŽĨ ƉƌĞƐƐŽƌƐƚƌĂĐŚĞĂů ŝŶƚƵďĂƟŽŶ ĂŶĚ ŵĞĐŚĂŶŝĐĂů ǀĞŶƟůĂƟŽŶ Group A Streptococcus pyogenes ǁĂƐ ƉƌĞƐĞŶƚ ŝŶ ŵƵůƟƉůĞ ďůŽŽĚ ĐƵůƚƵƌĞƐ ĂŶĚ ĚŝĂďĞƟĐ ŬĞƚŽĂĐŝĚŽƐŝƐ ǁĂƐ ĂůƐŽ ƉƌĞƐĞŶƚ ,Ğ ǁĂƐ ƐƵĐĐĞƐƐĨƵůůLJ ƚƌĞĂƚĞĚ ĞdžƚƵďĂƚĞĚ ĂŶĚ ĚŝƐĐŚĂƌŐĞĚ ƚŽ ŚŽŵĞ ϭϮ ĚĂLJƐ ĂŌĞƌ ĂĚŵŝƐƐŝŽŶ ŌĞƌ Ă ϯͲŵŽŶƚŚ ƉĞƌŝŽĚ ŽĨ ĐůŝŶŝĐĂů ƐƚĂďŝůŝƚLJ ŚĞ ĚĞǀĞůŽƉĞĚ ƐƵƐƚĂŝŶĞĚ ĚĞĐůŝŶĞ ŝŶ ĨŽƌĐĞĚ ĞdžƉŝƌĂƚŽƌLJ ǀŽůƵŵĞ ŝŶ ϭ ƐĞĐŽŶĚ ;&s Ϳ > ƐŚŽǁĞĚ ŵĞƚŚŝĐŝůůŝŶͲƐĞŶƐŝƟǀĞ Staphylococcus aureus ;D^^ Ϳ ĂŶĚ ŵƵĐŽŝĚ P. aeruginosad ĚŝĚ ŶŽƚ ƐŚŽǁ ĂĐƵƚĞ ƌĞũĞĐƟŽŶ Žƌ ŽƚŚĞƌ ƐƉĞĐŝĮĐ ƉĂƌĞŶĐŚLJŵĂů ĂďŶŽƌŵĂůŝƚLJ ŶƟďŝŽƟĐƐ ǁĞƌĞ ĂĚŵŝŶŝƐƚĞƌĞĚ ĂŶĚ ďůŽŽĚ ĐƵůƚƵƌĞƐ ŐƌĞǁ Candida albicans ĂŶĚ Stenotrophomonas maltophilia /ŶƚƵďĂƟŽŶ ĂŶĚ ŵĞĐŚĂŶŝĐĂů ǀĞŶƟůĂƚŽƌLJ ƐƵƉƉŽƌƚ ǁĞƌĞ ƌĞƋƵŝƌĞĚ ƵĞ ƚŽ ůĂĐŬ ŽĨ ŝŵƉƌŽǀĞŵĞŶƚ ǁŝƚŚ ĂƉƉƌŽƉƌŝĂƚĞ ĂŶƟďĂĐƚĞƌŝĂů ĂŶĚ ĂŶƟͲĨƵŶŐĂů ƚŚĞƌĂƉŝĞƐ Ă ƐƵƌŐŝĐĂů ůƵŶŐ ďŝŽƉƐLJ ǁĂƐ ƉĞƌĨŽƌŵĞĚ ƚŚĂƚ ƐŚŽǁĞĚ &KW ;&ŝŐƵƌĞ Ϯ ĂŶĚ Ϳ ŚĞƐƚ ŝŵĂŐŝŶŐ ƐŚŽǁĞĚ ƉĞƌƐŝƐƚĞŶƚ ŝŶĮůƚƌĂƚĞƐ ĂŶĚ ĐĂƌĞ ǁĂƐ ǁŝƚŚĚƌĂǁŶ ĂŌĞƌ ϭ ŵŽŶƚŚ ŽĨ ŵĞĐŚĂŶŝĐĂů ǀĞŶƟůĂƟŽŶ
Summary
ΚΘͲLJĞĂƌͲŽůĚ ĨĞŵĂůĞ ƌĞĐĞŝǀĞĚ Ă ŚĞĂƌƚůƵŶŐ ƚƌĂŶƐƉůĂŶƚ ĨŽƌ ĐŽŶŐĞŶŝƚĂů ŚĞĂƌƚ ĚŝƐĞĂƐĞ ĂƌůLJ ƐƉƵƚƵŵ ĐƵůƚƵƌĞƐ ĚĞŵŽŶƐƚƌĂƚĞĚ 'ƌĂŵͲŶĞŐĂƟǀĞ ƌŽĚƐ ĨŽƌ ǁŚŝĐŚ ƉŝƉĞƌĂĐŝůůŝŶͲƚĂnjŽďĂĐƚĂŵ ǁĂƐ ŐŝǀĞŶ ĂŶĚ ƐŚĞ ǁĂƐ ĞdžƚƵďĂƚĞĚ ŽŶ ƚŚĞ ƐĞĐŽŶĚ ĚĂLJ ƉŽƐƚͲƚƌĂŶƐƉůĂŶƚ ĂŶĚ ĐŽŵŵĞŶĐĞĚ ĂŵďƵůĂƟŽŶ ,ŽǁĞǀĞƌ ƐŵĂůů ďŽǁĞů ĐŽŵƉůŝĐĂƟŽŶƐ ĚĞǀĞůŽƉĞĚ ĂŶĚ ƌĞƋƵŝƌĞĚ ƐƵƌŐŝĐĂů ƌĞƐĞĐƟŽŶ ĂŶĚ ƐŚĞ ĚĞǀĞůŽƉĞĚ ĚŝĂůLJƐŝƐͲĚĞƉĞŶĚĞŶƚ ĂĐƵƚĞ ƌĞŶĂů ŝŶƐƵĸĐŝĞŶĐLJ /ŶƚƵďĂƟŽŶ ĂŶĚ ŵĞĐŚĂŶŝĐĂů ǀĞŶƟůĂƟŽŶ ǁĞƌĞ ƌĞƋƵŝƌĞĚ ŽŶ ĚĂLJ ϯϬ ĂŶĚ ĐŚĞƐƚ ŝŵĂŐŝŶŐ ƐŚŽǁĞĚ ƉĞƌƐŝƐƚĞŶƚ ĚŝīƵƐĞ ŝŶĮůƚƌĂƚĞƐ ;&ŝŐƵƌĞ ϭ ĂŶĚ Ϳd ƐŚŽǁĞĚ ŵŝŶŝŵĂů ĂĐƵƚĞ ƌĞũĞĐƟŽŶ ;'ƌĂĚĞ ϭϬͿ ^ŚĞ ǁĂƐ ĞdžƚƵďĂƚĞĚ ε ĚĂLJƐ ůĂƚĞƌ ďƵƚ ƌĞƋƵŝƌĞĚ ƌĞŝŶƚƵďĂƟŽŶ ;ƉŽƐƚͲƚƌĂŶƐƉůĂŶƚ ĚĂLJ ρΘͿ ĨŽƌ ƉƌŽŐƌĞƐƐŝǀĞ ƌĞƐƉŝƌĂƚŽƌLJ ĨĂŝůƵƌĞd ďŝŽƉƐLJ ƐŚŽǁĞĚ &KW ďƵƚ ĚŝĚ ŶŽƚ ƐŚŽǁ ĂĐƵƚĞ ƌĞũĞĐƟŽŶ ;&ŝŐƵƌĞ Ϯ ĂŶĚ Ϳ ĂŶĚ ĂŶ ĞŶĚŽŵLJŽĐĂƌĚŝĂů ďŝŽƉƐLJ ǁĂƐ ŶĞŐĂƟǀĞ ĨŽƌ ĐĂƌĚŝĂĐ ƌĞũĞĐƟŽŶůĂƉĂƌŽƚŽŵLJ ĂŶĚ ƌŝŐŚƚ ŚĞŵŝĐŽůĞĐƚŽŵLJ ǁĞƌĞ ƉĞƌĨŽƌŵĞĚ ĨŽƌ ƉĞƌƐŝƐƚĞŶƚ ǀŽůǀƵůƵƐ ;ƉŽƐƚͲƚƌĂŶƐƉůĂŶƚ ĚĂLJ ϭϬϬͿ >ƵŶŐ ĨƵŶĐƟŽŶ ǁŽƌƐĞŶĞĚ ĂŶĚ Citrobacter freundii ǁĂƐ ŝƐŽůĂƚĞĚ ĨƌŽŵ ďůŽŽĚ ĐƵůƚƵƌĞƐ >͕ ĂŶĚ ƵƌŝŶĞ ĐƵůƚƵƌĞƐ ZĞƐƉŝƌĂƚŽƌLJ ƐƚĂƚƵƐ ƉƌŽŐƌĞƐƐŝǀĞůLJ ǁŽƌƐĞŶĞĚ ĂŶĚ ůŝĨĞ ƐƵƉƉŽƌƚ ǁĂƐ ǁŝƚŚĚƌĂǁŶ
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