A 25-year-old gentleman, diagnosed at the age of 16 years in 2012 with stage IVB nodular sclerosing Hodgkin's Lymphoma (HL), was treated with 6 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine, followed by complete remission. He then had recurrence twice, the first time in 2013, for which he received salvage therapy with dexamethasone, high dose cytarabine, and cisplatin, and then in 2014, at the age of 18 years, when he received ifosfamide, carboplatin, and etoposide, followed the same year by autologous HSCT.
In 2017, he started having night sweats, back pain, and weight loss, and his positron emission tomography (PET) scan showed disease recurrence in supra and infradiaphragmatic regions as well as bone marrow lesions without evidence of lung involvement. The patient then received 6 cycles of brentuximab vedotin and bendamustine and underwent his second HSCT in the form of haplo-HSCT (half-matched) from his sister in April 2018, at the age of 22 years, and continued his maintenance on brentuximab.
In July 2018, he started having waxing and waning oral and cutaneous erythematous papules over the torso and extremities, with biopsy of the papules confirming it as cutaneous graft versus host disease (GVHD). He was given topical treatment and was started on dexamethasone syrup gargle and spit 10 mg 3 times daily for 1 month for oral cavity lesions with significant improvement. Meanwhile, he was still maintained on brentuximab.
In November 2018, he presented to the clinic for dyspnea and nonproductive cough, for which a computed tomographic (CT) scan of the chest was done and showed scattered ground glass opacities (GGO) in the lung bases bilaterally and mild diffuse bronchiectasis in all lobes (Figure 1). A spirometry was done which showed a new decreased forced vital capacity (FVC) of 67%, compared to a normal baseline prior to the transplant, and a low forced expiratory volume in 1 second (FEV1) of 40% and a low FEV1/FVC of 52% (Table 1). To note that all prior lung imaging and lung function testing was normal. In view of the spirometry results and findings of wheezing on lung examination, he was prescribed a short course of oral prednisone 40 mg that was tapered down then stopped over 2 weeks, oral moxifloxacin, along with vilanterol/fluticasone furoate and tiotropium bromide puffs with partial improvement. Upon follow-up on March 2019, he had persistent dyspnea, but denied the presence of cough or fever. A repeat CT scan of the chest showed development of new lower lobe predominant bilateral, peripheral, peribronchovascular consolidations in the areas of previously seen GGOs, with worsening traction bronchiectasis and evidence of a new architectural distortion (Figure 2), and a suspicion of organizing pneumonia was raised in the radiology report, with a suggestion of chronic pulmonary GVHD, and less likely infection or medication side effect. A list of the medications he was on, along with their pulmonary side effects is shown in Table 2. The patient refused to undergo a lung biopsy as advised to decide for immunosuppression or steroid course, and was prescribed a new course of levofloxacin.
In May 2019, he presented back with fever, worsening dyspnea and a new productive cough of yellowish sputum. His procalcitonin level was also elevated of 9.4 ng/mL (normal laboratory value <0.05 ng/mL). A new CT scan of the chest showed further worsening in bilateral, mid-lung predominant consolidations and ground glass opacities, with changes of traction bronchiectasis and appearance of new cystic changes (Figure 3). A bronchoscopy with broncho-alveolar lavage (BAL) was done and detected the following: Para-influenza virus 2 on respiratory polymerase chain reaction (PCR) panel, gram negative rods on Gram stain, and one colony of Aspergillus species on fungal culture. Serum Aspergillus galactomannan was positive with a high index of 1.1 (normal laboratory index expected to be less than 0.5). In addition, the BAL cytology was reported as chronic inflammation with >90% lymphocytes and no malignant cells. Of note that Tuberculosis (TB) and Cytomegalovirus (CMV) PCR, Pneumocystis Jirovecii (PJP) PCR, mycobacterial culture, and Aspergillus galactomannan taken in BAL were all negative. Intravenous (IV) meropenem was given for 7 days for bacterial pneumonia and voriconazole 200 mg orally twice daily for 8 weeks was given for possible pulmonary aspergillosis. Both prophylactic Trimethoprim/sulfamethoxazole and Valacyclovir were added and his home inhalers were continued with significant improvement upon hospital discharge. He also finished his consolidation treatment with brentuximab the same month and his lymphoma was in complete remission.
At this point, the diagnosis of pulmonary fibrosis secondary to recurrent pulmonary infections versus chronic pulmonary GVHD in the form of organizing pneumonia was entertained, however, systemic steroid treatment was deferred in view of his active pulmonary fungal infection.
In August 2019, he was admitted again for fever and worsening dyspnea, found to have worsening upper lobes predominant pulmonary fibrotic changes and Influenza B infection for which he was treated with Oseltamivir, IV Piperacilin-tazobactam, and Levofloxacin. He was also started on oral prednisone 1 mg/kg daily with slow taper by 10 mg every 1 month, for a presumed diagnosis of organizing pneumonia, and he was maintained on prednisone for several months with inability to wean them off due to recurrence of dyspnea.
Subsequent pulmonary imaging over the following year showed a steady progression of his consolidations and traction bronchiectasis, significant decrease in ground-glass abnormalities throughout both lungs, a decrease in FDG uptake indicative of decrease in the inflammatory process and formation of scar tissue with a remarkable spatial shift to the mid and upper lung zones and progressive appearance of new cystic lesions in the upper lobes bilaterally (Figure 4). His pulmonary function test (PFT) also showed further significant drop in his FEV1, and to a greater extent, his FVC (Figure 1).