Table 2.
Published Case Reports of Infection With GM-CSF Autoantibodies
| Author & Year | Age/Sex/Ethnicity | Presenting Signs/Symptoms | Infection/Pathogen | Elevated GM-CSF Autoantibodies | Treatment | Duration of Follow-up | Outcome |
|---|---|---|---|---|---|---|---|
| Cryptococcus | |||||||
| Kuo 2021 [16] | 52/M/Asian | Persistent cough | C. gattii (pulmonary, CNS) | Yes | LAmB and flucytosine, then LAmB and fluconazole, then fluconazole (durations not specified) | 2–4 y following C. gattii Dx | Gradual resolution of symptoms; remains on antifungal treatment |
| Kuo 2021 [16] | 61/M/Asian | Progressive cough, intermittent fever, headache | C. gattii (pulmonary, CNS) | Yes | Amphotericin B and flucytosine ×3 wk, then fluconazole ×1 y; 5 mo later, fluconazole reinitiated x1 y | 2–4 y following C. gattii Dx | Recovered; fluconazole reinitiated for additional 1 y (starting 5 mo after initial treatment) for persistent antigenemia and unresolved focal opacity on chest X-ray |
| Kuo 2021 [16] | 71/F/Asian | Mass on dorsal right scapula (history of cancer, diabetes mellitus) | C. gattii (bone) | Yes | Fluconazole ×1 y | 2–4 y following C. gattii Dx | Recovered |
| Kuo 2021 [16] | 39/M/Asian | Chronic dyspnea on exertion | C. gattii (pulmonary) | Yes | Fluconazole and flucytosine, then fluconazole ×1 y | 2–4 y following C. gattii Dx | Recovered |
| Kuo 2021 [16] | 46/M/Asian | Fever, progressive right upper quadrant abdominal pain | C. gattii (pulmonary) | Yes | Amphotericin B and flucytosine, then fluconazole (durations not specified) | 2–4 y following C. gattii Dx | Recovered |
| Stevenson 2019 [38] | 48/M/NS | Hemoptysis, right upper lobe cavitating mass extending to upper bronchus; 1 y later relapsed with acute CNS deficits, cryptococcoma, concomitant mild cryptococcal meningoencephalitis, and aPAP | C. gattii (pulmonary, intracranial) | Yes | Amphotericin B ×2 wk, then fluconazole ×8 mo; 1 y later, LAmB and flucytosine x1 wk, then high dose fluconazole x 4 mo, then fluconazole prophylaxis (ongoing) | 3.5 y | Initial pulmonary symptoms resolved; 1 y later relapsed with CNS infection, now with symptom resolution; remains on long-term fluconazole prophylaxis |
| Stevenson 2019 [38] | 43/M/Asian | Complex right superior cerebellar mass, with small spiculated right upper lobe lesion on chest CT scan | C. gattii (intracranial) | Yes | Occipital craniotomy and resection of mass; amphotericin B and flucytosine ×2 wk, then fluconazole ×3 wk, then voriconazole x4 mo, then posaconazole x20 mo (and ongoing) |
20 mo | Postoperative appearance as expected on brain MRI with no new lesions; patient remains well and continues long-term posaconazole therapy |
| Demir 2018 [15] | 42/M/NS | Fever, headache, weight loss, peripheral facial paralysis | C. gattii (pulmonary, CNS) | Yes | Multiple antifungal regimens (including fluconazole, LAmB, and voriconazole) for nearly 5 y |
6 y | Developed aPAP 3 y after cryptococcal meningitis, at which time BAL microbial cultures were negative; near-complete spontaneous regression of aPAP 3 y later |
| Crum-Cianflone 2017 [39] | 42/M/Caucasian | Acute lower extremity paralysis, chronic cough, progressive constipation |
C. gattii (CNS) | Yes | LAmB and flucytosine ×8 wk, then fluconazole | ~3 mo | Clinical improvement; remains on fluconazole prophylaxis |
| Crum-Cianflone 2017 [39] | 34/M/Hispanic | Slowly enlarging facial lesion, weight loss, night sweats, mild headaches, bilateral visual acuity loss | C. gattii (pulmonary, skin, intracranial) | Yes | Craniotomy with debridement of frontal lesion; LAmB and flucytosine ×10 wk, then fluconazole ×12 mo | ~1 y | Remains on fluconazole prophylaxis |
| Rosen 2013 [21] | 31/F/NS | Headache | C. gattii (pulmonary, CNS) | Yes | Amphotericin B and flucytosine x8 d, then fluconazole and flucytosine (durations not specified) | 5 mo | Resolution of cryptococcoma; remains on fluconazole |
| Viola 2021 [24] | 26/M/NS | Ulnar osteolytic lesion, upper lobe lung mass, mediastinal lymphadenopathy | C. neoformans (pulmonary, bone, CNS) | Yes | LAmB and flucytosine ×5 d, then LAmB and fluconazole ×6 wk, then high-dose fluconazole ×6 mo | 3 y | Relapsed within 3 mo, likely due to underlying osseous fungal sequestration |
| Perrineau 2020 [40] | 41/F/NS | Headache, vomiting, confusion, photophobia | C. neoformans (CNS) | Yes | LAmB and flucytosine ×2 wk, then fluconazole ×2 wk | ~6 mo | Meningeal syndrome relapse after 8 wk, with cerebral vasculitis; treated with high-dose fluconazole and corticosteroids |
| Panackal 2017 [22] | 73/M/NS | Fever, headache, myalgia, diplopia | C. neoformans (CNS) | Yes | Antifungals (details not specified) | NS | Responded |
| Rosen 2013 [21] | 20/F/NS | Headache, fever, neck pain, diplopia, confusion | C. neoformans (pulmonary, CNS) | Yes | Amphotericin B and flucytosine, then fluconazole (durations not specified) | 3 y | Recovered; developed aPAP 2 y later (WLL required) |
| Rosen 2013 [21] | 47/M/Hispanic | Cough, weakness, tremors | C. neoformans (pulmonary, CNS, skin, blood) | Yes | Amphotericin B x2 wk, then fluconazole (ongoing) | NS | Recovered; remains on maintenance fluconazole; subsequently diagnosed with aPAP |
| Rosen 2013 [21] | 48/M/Asian | Fever, cough, back pain | C. neoformans (pulmonary, CNS); Mycobacterium tuberculosis (pulmonary) | Yes | Amphotericin B, then fluconazole and antituberculosis therapy x9 mo | 2 y | Recovered |
| Applen Clancey 2019 [23] | 69/M/NS | Headache, clumsiness, vertigo, shuffling gait, memory deficits, worsening motor skills | C. deuterogattii (CNS) | Yes | LAmB and flucytosine ×4 wk, then LAmB and fluconazole ×2 wk, then LAmB and flucytosine ×2 wk, then fluconazole ×12 wk | 10 mo | Responded; remains on maintenance fluconazole |
| Kuo 2021 [16] | 49/M/Asian | Persistant dry cough and chest pain | Cryptococcus (pulmonary) | Yes | Fluconazole (ongoing; duration not specified) | 2–4 y | Antifungal treatment continuing |
| Nocardia | |||||||
| Wu 2021 [41] | 45/M/Asian | Activity-related respiratory exertion, persistent cough (aPAP) |
Nocardia (pulmonary) | Yes | Sulfamethoxazole ×6 mo | 16 mo | Eventual improvement in lung function and chest imaging without need for WLL |
| Berthoux 2020 [12] | 40/M/NS | Subacute left brachiofacial deficit and headaches (parietal cerebral abscess, aPAP) | Nocardia (intracranial) | Yes | Meropenem ×6 wk and high-dose trimethoprim/sulfamethoxazole ×1 y, then trimethoprim/sulfamethoxazole prophylaxis (ongoing) | 18 mo | Clinical improvement, with total neurological recuperation and complete regression of cerebral abscess; for aPAP, sargramostim (SC), with subsequent WLL and rituximab |
| Ekici 2020 [42] | 62/M/NS | Fever, night sweats, chest pain, cavitary nodular infiltrates, “relapsing pneumonias”; multiple pulmonary masses on chest CT (aPAP) | Nocardia brasiliensis (pulmonary) | Yes | Amikacin and trimethoprim/sulfamethoxazole ×6 wk, then moxifloxacin and trimethoprim/sulfamethoxazole ×6 mo | 6 mo | Lung function tests and chest CT normalized, with full resolution of prior pulmonary masses; treated with CyBorD chemotherapy for MGUS; masses remain decreased 1 y following CyBorD therapy |
| Yamaguchi 2010 [43] | 37/M/NS | Persistent cough, sputum (aPAP) | Nocardia (pulmonary) | Yes | Antituberculosis therapy and antibiotics (details not specified) | NS | aPAP rapidly worsened with exacerbation of pulmonary nocardiosis but improved after treating infection |
| Mycobacterium | |||||||
| Shiohira 2021 [44] | 63/M/NS | Exacerbating aPAP | Mycobacterium avium complex (pulmonary) | Yes | Rifampicin, ethambutol, and clarithromycin ×12 mo | 1 y | Resolution of MAC infection with no subsequent recurrence; WLL upon aPAP relapse |
| Price 2006 [45] | 13/F/African Canadian | aPAP, history of cough (6 mo), developmental delay |
Mycobacterium avium
intracellulare (pulmonary) |
Yes | WLL, followed by sargramostim (inhaled) twice daily ×12 mo (decreased to once daily after 4 mo) for aPAP; no anti-infectives administered | 15 mo | Resolution of infection with improvement in lung function and chest imaging; resumption of normal development |
| Aspergillus | |||||||
| Arai 2015 [46] | 59/M/NS | Persistent cough, history of tuberculosis | Aspergillus fumigatus (pulmonary) | Yes | Initially treated with itraconazole ×2 y before aPAP Dx, rhu GM-CSF (SC) ×8 wk following aPAP Dx, then micafungin and amphotericin B |
3 y | Initial reduction of infection followed by relapse; patient died of respiratory failure 4 mo after initiation of aPAP therapy |
Abbreviations: aPAP, autoimmune pulmonary alveolar proteinosis; BAL, bronchoalveolar lavage; CNS, central nervous system; CT, computed tomography; CyBorD, cyclophosphamide, bortezomib, and dexamethasone; Dx, diagnosis; GM-CSF, granulocyte-macrophage colony-stimulating factor; LAmB, liposomal amphotericin B; MGUS, monoclonal gammopathy of undetermined significance; MRI, magnetic resonance imaging; NS, not specified; PAP, pulmonary alveolar proteinosis; rhu, recombinant human; SC, subcutaneous; WLL, whole lung lavage.