Monoclonal antibodies in idiopathic chronic eosinophilic pneumonia: a scoping review.

BACKGROUND: Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare disease characterized by pulmonary radiological alterations, peripheral eosinophilia, and demonstrated pulmonary eosinophilia. Oral steroids (OSs) are the standard management, but relapses occur in up to 50% of patients during the decrease or suspension of steroids, usually requiring reinitiation of treatment, exposing patients to secondary events derived from the management. Management with monoclonal antibodies has been proposed in these cases to control the disease and limit the secondary effects. The objective is to describe the extent and type of evidence regarding the use of monoclonal antibodies for ICEP. METHODS: A panoramic review of the literature was performed. Observational and experimental studies of pediatric and adult populations that managed recurrent ICEP with monoclonal antibodies were included. Data search, selection, and extraction were performed by two independent reviewers. RESULTS: 937 studies were found. After applying the inclusion and exclusion criteria, 37 titles remained for the final analysis: a retrospective, observational, real-life study, two case series publications, and 34 case reports published in academic poster sessions and letters to the editor. In general, the use of monoclonal antibodies approved for severe asthma could be useful for the control of ICEP, since most of the results show a good response for clinical and radiological outcomes. Biological drugs seem to be a safer option for controlling relapses in ICEP, allowing lowering/suspension of OSs, and sometimes replacing them in patients intolerant to them, patients with significant comorbidities, and patients who have already developed adverse events. CONCLUSION: The extent of the evidence supporting management of ICEP with monoclonal antibodies against IL-5 and IgE (omalizumab) is limited, but it could be promising in patients who present frequent relapses, in cortico-dependent individuals, or in patients in whom the use of steroids is contraindicated. The extent of the evidence for management with dupilumab is more limited. Studies with better design and structure are needed to evaluate quality of life and outcomes during a clear follow-up period. To our knowledge, this is the first scoping review of the literature showing the extent of the evidence for the management of ICEP with monoclonal antibodies.

Dupilumab suppresses relapsing chronic eosinophilic pneumonia with severe asthma.

Dupilumab-induced hypereosinophilia is mediated by blockade of the IL-4/IL-13 pathway, which reduces eosinophil migration from peripheral blood. The increase in peripheral blood eosinophils may lead to chronic eosinophilic pneumonia (CEP) and/or eosinophilic granulomatosis with polyangiitis, but a direct causal connection between dupilumab and eosinophilic lung diseases has not been established. A 33-year-old Japanese woman with bronchial asthma since age three was treated with fluticasone propionate plus salmeterol twice daily after several asthma exacerbations at age 17. Her course was complicated by CEP at age 33 which resolved without the need for systemic steroids. However, in the four months following resolution of her CEP, the patient had three asthma exacerbations, and a recurrence of CEP, with blood leukocytes of 8500/µL, of which 25.0% were eosinophils. She was treated with prednisolone 50 mg/day, but she could not continue this dose due to the onset of myalgia. Then she had relapsing CEP twice within three months. She was treated with prednisolone 15 mg/day for CEP, but she had persistent asthma for more than one month; dupilumab was added at 600 mg, followed by 300 mg every two weeks. In the first month of treatment with dupilumab, the patient's asthma symptoms resolved completely, and she had only one relapse of CEP. In 12 months of follow-up, she had neither an asthma exacerbation nor another relapse of CEP. Dupilumab may be a promising treatment for patients with refractory asthma complicated by recurring CEP and undesirable steroid side effects.

Chronic eosinophilic pneumonitis due to the inhalation of aerosolized face lotion: A case report.

RATIONALE: Inhalation of toxic agents can induce eosinophilic pneumonia. However, only a few case reports demonstrate that exposure to materials can induce chronic eosinophilic pneumonia (CEP). Here, we describe a rare case of CEP with mild alveolar hemorrhage due to the inhalation of aerosols from face lotion. This is the first report of eosinophilic pneumonia caused by face lotion exposure. PATIENT CONCERNS: A 39-year-old woman was admitted to our hospital with cough and dyspnea for 2 months, which coincided when she started to use a new aerosolized face lotion. Laboratory findings showed high blood eosinophil levels, and chest computed tomography (CT) scans revealed bilateral peripheral consolidation and ground-glass opacity mainly in the left upper lobe. She underwent flexible bronchoscopy. Eosinophils in bronchoalveolar lavage fluid (BALF) were slightly elevated, and the gross appearance of BALF was bloody. The histological examination of the transbronchial lung biopsy showed infiltration of eosinophils and macrophages in alveolar septa with edema and without vasculitis and granuloma formation; a small number of hemosiderin-laden macrophages were also observed. An inhalation challenge test involving the face lotion was performed. Six hours after the test, the blood test showed an increased white blood cell (WBC) count, and chest radiography showed slight exacerbation. Forced vital capacity decreased the following day. DIAGNOSIS: According to histological analysis and positive result of an inhalation challenge test, she was diagnosed with CEP with mild alveolar hemorrhage due to inhalation of aerosols from the face lotion. INTERVENTIONS AND OUTCOMES: She gradually improved without medication after stopping the use of face lotion. LESSONS: To the best of our knowledge, this is the first report of CEP with mild alveolar hemorrhage due to the inhalation of face lotion. Various inhaled agents, such as face lotion, can induce CEP in rare cases.

Diffuse alveolar haemorrhage in the setting of eosinophilic pneumonia.

A 65-year-old woman who presented with a constellation of symptoms, including cough with haemoptysis, fever, chills and hypoxia along with weight loss, was found to have diffuse alveolar haemorrhage. After a myriad of investigations returned normal, an open lung biopsy was performed, which revealed the diagnosis to be subacute eosinophilic pneumonia. This is one of its kind of rare presentations where eosinophilic pneumonia presents as diffuse alveolar haemorrhage and has been reported only five times prior to this.

Biologics for oral corticosteroid-dependent asthma.

Background: Oral corticosteroid (OCS) dependent asthma is one of the severe asthma phenotypes that requires personalized treatment. Objective: To review the role of biologic treatments in OCS-dependent asthma. Methods: A nonsystematic review was performed of emerging multiple novel biologics for potential treatment of OCS-dependent asthma. Results: The serious adverse effects of OCS can be seen as a result of their regular long-term administration. Anti-interleukin (IL) 5 (mepolizumab), anti-IL-5R (benralizumab), and anti-IL-4Rα (dupilumab) are the therapies of choice for OCS-dependent severe asthma. Results of studies showed the efficacy of mepolizumab, benralizumab, and dupilumab, especially in patients with the OCS-dependent severe eosinophilic asthma phenotype and with nasal polyps. Dupilumab may be the therapy of choice of monoclonal antibodies in cases of moderate-severe atopic dermatitis accompanied by OCS-dependent severe asthma. For reslizumab and omalizumab, placebo controlled double-blind studies conducted with OCS-dependent patient populations are needed. Conclusion: Biologics are effective in the "OCS-dependent asthma" phenotype as add-on therapy. It seems that chronic OCS use in OCS-dependent asthma will be replaced by biologic agents that specifically target type 2 inflammation, along with a much better safety profile. However, real-life studies that compare these biologics in OCS-dependent severe asthma are urgently needed.

Real-World Effectiveness and the Characteristics of a "Super-Responder" to Mepolizumab in Severe Eosinophilic Asthma.

BACKGROUND: Mepolizumab was the first licensed anti-IL5 monoclonal antibody for severe eosinophilic asthma (SEA). To date there are few data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response. RESEARCH QUESTION: How do patients with severe eosinophilic asthma respond to mepolizumab in the real world setting and which characteristics are associated with a super-response to this therapy? STUDY DESIGN AND METHODS: We conducted a retrospective review of all patients who received at least 16 weeks of treatment with mepolizumab (100 mg subcutaneously) for SEA at our regional asthma center in the United Kingdom. Clinical data were collected at each 4-week visit. At 16, 24, and 52 weeks, patients were classified as "responders" or "nonresponders." A response was defined as ≥50% reduction in exacerbations; for patients whose condition requires maintenance oral corticosteroids (mOCS), a response was defined as ≥50% reduction in prednisolone dose. Super responders were defined as exacerbation-free and off mOCS at one year. RESULTS: Ninety-nine patients were included in the analysis. Asthma exacerbations decreased from a baseline of 4.04 ± 2.57 to 1.86 ± 2.17 per year at one year (54% reduction; P < .001). Sixty-eight patients were receiving mOCS at the time of commencing mepolizumab. By one year, the daily median dose fell from 10 mg (interquartile range, 10 to 15) to 0 mg (interquartile range, 0 to 10; P < .001). Fifty-seven percent of them were able to discontinue mOCS; 72.7% (95% CI, 63.0 to 80.7) of the patients were classified as responders, and 28.3% (95% CI, 20.2 to 38.0) of the patients were classified as super responders. Baseline characteristics associated with responder and super responder status included the presence of nasal polyposis (P = .012), lower baseline Asthma Control Questionnaire 6 (P = .006), a lower BMI (P = .014), and, in those patients receiving mOCS, a significantly lower prednisolone dose at baseline (P = .005). At 16 weeks, the one-year responder status was correctly identified in 80.8% patients; by 24 weeks, this status rose to 92.9%. INTERPRETATION: In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI, and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in >90% of patients by week 24.

Idiopathic acute eosinophilic pneumonia: A rare cause of hypoxic respiratory failure.

Idiopathic Acute Eosinophilic Pneumonia (IAEP) is a life-threatening cause of hypoxic respiratory failure. IAEP is challenging to diagnose as it may mimic infectious pneumonia or acute respiratory distress syndrome. Distinguishing IAEP from these alternatives is important; the mainstay of treatment for IAEP is corticosteroids, a therapy which might not otherwise be indicated. Patients treated appropriately usually experience a full recovery. In this case report we describe the presentation, evaluation, and management of a 19-year old male who presented to the emergency department (ED) in respiratory failure from IAEP. The patient was a military trainee who recently moved to the United States from Saudi Arabia. He also recently began smoking cigarettes for the first time, a known risk factor for IAEP. Upon initial presentation, the patient was in respiratory distress and had an oxygen saturation of 82% on room air. His ED diagnostic workup included chest X-ray showing diffuse interstitial thickening and chest computed tomography that demonstrated diffuse nodular opacification of pulmonary parenchyma. The patient was admitted to the intensive care unit (ICU) where bronchoscopy yielded cytology with 30% eosinophilia. The patient ultimately required 3 days of extra corporeal membrane oxygenation (ECMO) due to worsening hypoxic respiratory failure. After both intravenous and outpatient oral steroid treatments, the patient went on to have a full recovery with no ongoing respiratory issues. To our knowledge, this is the first case of IAEP requiring ECMO reported in the emergency medicine literature.

Diagnostic pitfalls of acute eosinophilic pneumonia in an adolescent boy following cigarette smoking: A case report.

RATIONALE: Acute eosinophilic pneumonia (AEP) is characterized by acute febrile respiratory symptoms, bilateral lung infiltrates, and pulmonary eosinophilia. AEP is closely related to cigarette smoking but is rarely suspected in pediatric cases despite the fact that there is a relatively high incidence of cigarette smoking among adolescents in Taiwan. PATIENT CONCERNS: We report a case of a previously healthy 15-year-old boy who presented with fever and acute progressive dyspnea. Due to lack of awareness of cigarette smoking history in adolescents and the nonspecific signs and symptoms of AEP at early stages, the patient was initially treated as community-acquired pneumonia (CAP) but was unresponsive to antibiotics treatment. DIAGNOSES: A combination of a recent onset smoking history and pulmonary eosinophilia on bronchoalveolar lavage confirmed the diagnosis of cigarette-induced AEP. INTERVENTIONS: Corticosteroid treatment was prescribed. OUTCOMES: The condition improved within 24 hours, with resolution of alveolar infiltrates on chest radiographs. LESSONS: With the increasing incidence of smoking amongst adolescents in Taiwan, careful history questioning regarding cigarette smoking is necessary. Due to similarities in initial clinical and radiographic features of AEP and CAP, adolescents with suspected CAP who are unresponsive to antibiotic treatment but have a subsequent rise in peripheral eosinophils should raise the clinician's suspicion of AEP related to cigarette smoking.

Last station in the eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis march: Eosinophilic asthma with radiological findings associated with blood eosinophilia.

OBJECTIVE: Eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis (EA-CRS/NP) is a subphenotype of adult-onset eosinophilic asthma. Blood eosinophil levels are shown to be highly elevated in patients with EA-CRS/NP and have potential for tissue infiltration. We aimed to demonstrate the clinical features of the patients who have a blood eosinophil level above 10% and have thorax computed tomography findings due to blood eosinophilia. METHODS: Patients who were followed up in our clinic between 2012 and 2017 were retrospectively evaluated. Inclusion criteria were as follows: 1) Eosinophilic severe asthma, 2) eosinophilia >10%, 3) chronic sinusitis and/or nasal polyps, 4) patients with pathologic findings on thorax computed tomography, 5) regular follow-up for at least 1 year. RESULTS: We identified 36 patients who met the above criteria. We defined this group as "Eosinophilic Asthma with chronic Rhinosinusitis and/or nasal polyposis with Radiological findings related to blood eosinophilia" (EARR). The mean age was 44.9 ± 11 years and 64% were females. Nasal polyps, aspirin exacerbated respiratory disease, and atopy, were present in 81%, 47%, and 25% of the patients, respectively. The mean blood eosinophil count was 1828.6 cells/mm3 (19%). The majority of EARR patients had upper lobe dominant ground-glass opacities. The mean follow-up period was 3.2 ± 2.5 years. EARR patients did not evolve into eosinophilic granulomatous polyangiitis in the follow-up. CONCLUSIONS: This phenotype is the first eosinophilic asthma sub-phenotype reported in the literature. EARR is the final stage of the allergic march of EA-CRS/NP.

Reflux aspiration in lungs of dogs with respiratory disease and in healthy West Highland White Terriers.

BACKGROUND: Gastroesophageal reflux and microaspiration (MA) of gastric juice are associated with various human respiratory diseases but not in dogs. OBJECTIVE: To detect the presence of bile acids in bronchoalveolar lavage fluid (BALF) of dogs with various respiratory diseases. ANIMALS: Twenty-seven West Highland White Terriers (WHWTs) with canine idiopathic pulmonary fibrosis (CIPF), 11 dogs with bacterial pneumonia (BP), 13 with chronic bronchitis (CB), 9 with eosinophilic bronchopneumopathy (EBP), 19 with laryngeal dysfunction (LD), 8 Irish Wolfhounds (IWHs) with previous BPs, 13 healthy WHWTs, all privately owned dogs, and 6 healthy research colony Beagles METHODS: Prospective cross-sectional observational study with convenience sampling of dogs. Bile acids were measured by mass spectrometry in BALF samples. Total bile acid (TBA) concentration was calculated as a sum of 17 different bile acids. RESULTS: Concentrations of TBA were above the limit of quantification in 78% of CIPF, 45% of BP, 62% of CB, 44% of EBP, 68% of LD, and 13% of IWH dogs. In healthy dogs, bile acids were detected less commonly in Beagles (0/6) than in healthy WHWTs (10/13). Concentrations of TBA were significantly higher in CIPF (median 0.013 µM, range not quantifiable [n.q.]-0.14 µM, P < .001), healthy WHWTs (0.0052 µM, n.q.-1.2 µM, P = .003), LD (0.010 µM, n.q.-2.3 µM, P = .015), and CB (0.0078 µM, n.q.-0.073 µM, P = .018) groups compared to Beagles (0 µM, n.q.). CONCLUSION AND CLINICAL IMPORTANCE: These results suggest that MA occurs in various respiratory diseases of dogs and also in healthy WHWTs.

Indeterminate dendritic cell neoplasm accompanied by eosinophilic pneumonia successfully treated by systemic steroid therapy: Report of the first case with muscular and parotid involvement and review of published work.

A 34-year-old Japanese man presented with an indolent nodule on the right flank. Computed tomography of the chest and abdomen demonstrated a large nodule measuring 55 mm × 50 mm in the abdominal oblique muscle layer of the right flank, and several small nodules were seen in the muscle layer throughout the body and subcutaneous tissue of the lower abdomen. 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography revealed nodular lesions in the bilateral parotid glands, bilateral cervical lymph nodes and lower lobe of the right lung. Intermittently, ground-glass shadows developed in the bilateral lungs. Histologically, sheet-like nodules in the abdominal oblique muscle layer and parotid gland were composed of large polygonal cells with convoluted nuclei and ample eosinophilic cytoplasm. Several lymphocytes and considerable eosinophils were intermingled. Lung biopsy demonstrated an inflammatory infiltrate of lymphocytes and considerable eosinophils in the alveoli. Immunohistochemically, polygonal cells were positive for S100 protein and CD1a, but negative for langerin and BRAFV600E . Some cells were positive for CD68. Electron microscopy demonstrated histiocytic cells with phagosomes and interdigitating processes. However, no Birbeck granules were observed. Eosinophilia was seen in the peripheral blood. Multifocal nodules and ground-glass shadows gradually diminished following systemic administration of oral prednisolone. We describe a case of indeterminate dendritic cell neoplasm with multifocal involvement of the muscle, subcutis, lymph node and parotid gland accompanied by chronic eosinophilic pneumonia that was successfully treated by systemic steroid therapy. Neither muscular nor parotid indeterminate dendritic cell neoplasms accompanied by eosinophilic pneumonia have been previously reported.

[Vasculitides and eosinophilic pulmonary diseases]. / Vaskulitiden und eosinophile Lungenerkrankungen.

Eosinophilic granulocytes form peripheral effector cells controlled by Th2 lymphocytes, which cause local cell, tissue, and functional disorders of infiltrated organs via the release of cytotoxic basic proteins and oxygen radicals. Diseases associated with eosinophilia include systemic and organ-related forms. The lungs are involved in eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome), acute and chronic eosinophilic pneumonia, as well as in an organ manifestation in hypereosinophilic syndrome and certain parasitic diseases. In particular, the lungs are frequently affected in vasculitis of small vessels, including EGPA, granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). Among these, EGPA is the most frequent pulmonary eosinophil vasculitis representative. In addition, there are various overlap syndromes in which characteristic features of EGPA can be detected in the context of other anti-neutrophil cytoplasmic antibody (ANCA-)associated vasculitides. Occasionally, non-ANCA-associated pulmonary vasculitides occur with eosinophilia (e.g., Schönlein-Henoch purpura, Kawasaki disease, drug-induced hypersensitivity, and paraneoplastic syndrome). Herein, the pulmonary vasculitides accompanying eosinophilia are presented with respect to both the lung manifestations and pulmonary eosinophilia.

Conjunctival Eosinophilic Masses With Chronic Eosinophilic Pneumonia.

PURPOSE: To report a case of ocular findings associated with chronic eosinophilic pneumonia (CEP). CASE: A 63-year-old man was referred to the National Institution of Hospital Organization Tokyo Medical Center with bilateral eyelid swelling due to giant papillomatous changes, each measuring approximately 10 mm in diameter with severe hyperemia on the tarsal conjunctiva. He was followed for CEP for 8 years and systemically treated with 6 mg oral prednisolone for an average of 5 years. Because the lesions did not respond to topical 0.1% tacrolimus and 0.025% levocabastine treatment and because an increase in intraocular pressure was found to occur as a side effect of 0.01% betamethasone instillation for several months, we performed surgical resection of the bilateral conjunctival lesions. Histopathological findings revealed extreme eosinophil, plasma cell, and lymphocytic infiltration and interstitial fibrosis. These conjunctival specimen findings were similar to those seen in the alveolar lesions in CEP. Topical antiinflammatory therapy using 0.1% tacrolimus eye drops was administered after surgery, which relieved the patient's lid swelling and itching. However, the lesions concurrently changed to be consistent with exacerbation and remission of systemic CEP. CONCLUSIONS: Based on the clinical course and histopathology, the conjunctival proliferative masses in our case were assumed to be associated with CEP.

BILATERAL CENTRAL RETINAL VEIN OCCLUSIONS IN A YOUNG PATIENT WITH A HISTORY OF EOSINOPHILIC PNEUMONIA AND THALAMIC STROKE.

PURPOSE: To describe a case of a central retinal vein occlusion in a young patient with a history of eosinophilic pneumonia. METHODS: A retrospective case report of a 45-year-old woman with acute painless vision loss for 9 days after multiple episodes of eosinophilic pneumonia and thalamic stroke. Fluorescein angiography, spectral domain optical coherence tomography, and clinical examination were performed. She was then treated with intravitreal bevacizumab and pan-retinal photocoagulations. RESULTS: Retinal examination revealed tortuosity and dilatation of all branches of the central retinal vein and flame-shaped hemorrhages in all four quadrants of the right eye associated with cystoid macular edema, optic disc edema, and cotton wool spots. The left eye had mild venous dilatation and tortuosity with a few dot retinal hemorrhages in the far temporal periphery. The cystoid macular edema resolved after one intravitreal injection of bevacizumab and remained resolved at the most recent follow-up. Fluorescein angiography at the most recent follow-up revealed vasculitis in the far periphery of the nontreated eye. CONCLUSION: Central retinal vein occlusion in young patients is a rare condition often presenting as a manifestation of an underlying inflammatory or hematological disorder. Combined anti-vascular endothelial growth factor treatment and pan-retinal photocoagulation may have resolved the associated cystoid macular edema in this case, although continued observation is necessary.

In vivo neutralization of α4 and ß7 integrins inhibits eosinophil trafficking and prevents lung injury during tropical pulmonary eosinophilia in mice.

Integrins regulate leukocyte trafficking during homeostasis and inflammatory conditions. However, the role of α4 and ß7 integrins in guiding eosinophil transmigration into the lungs during filarial manifestation of Tropical Pulmonary Eosinophilia (TPE) has not been explored. In this study, mice exhibiting TPE manifestations were administered with in vivo neutralizing antibodies against integrins α4 and ß7 or their combination and immuno-pathological parameters were evaluated. Results show an intact lung barrier, significantly lower lung inflammation and reduced eosinophil counts in the Bronchoalveolar lavage fluid and lungs of mice receiving anti-α4+ ß7 treatment. Reduced eosinophil peroxidase and ß-hexosaminidase activity, downregulation of inflammatory genes, lower production of inflammatory lipid intermediates like prostaglandins E2 and D2, leukotriene B4 and cysteinyl leukotrienes were also noted in anti-α4+ ß7 treated mice. Reduced accumulation of central memory, effector memory, regulatory T cells and lower production of IL-4, IL-5, and TGF-ß were other cardinal features of anti-α4+ ß7 treated mice lungs. Flow cytometry-sorted lung eosinophils from anti-α4+ ß7 treated mice showed higher apoptotic potential, downregulated anti-apoptotic gene Bcl-2, and exhibited reduced F-actin polymerization and calcium influx as compared to IgG controls. In summary, neutralization of α4+ ß7 integrins impairs the transmigration, activation and survival of eosinophils and reduces TPE induced pathology in mice lungs.

Invasive pulmonary mucormycosis: rare presentation with pulmonary eosinophilia.

BACKGROUND: Fungi can cause a variety of infectious diseases, including invasive mycosis and non-invasive mycosis, as well as allergic diseases. The different forms of mycosis usually have been described as mutually exclusive, independent entities, with few descriptions of overlapping cases. Here, we describe the first reported case of a patient with the complication of pulmonary eosinophilia in the course of invasive mucormycosis. CASE PRESENTATION: A 74-year-old Japanese man with asthma-COPD overlap underwent emergency surgery for a ruptured abdominal aortic aneurysm. The surgery was successful, but fever and worsening dyspnea appeared and continued from postoperative day (POD) 10. A complete blood count showed leukocytosis with neutrophilia and eosinophilia, and the chest X-ray showed consolidation of the left upper lung at POD 15. We suspected nosocomial pneumonia together with an exacerbation of the asthma-COPD overlap, and both antibiotics and bronchodilator therapy were initiated. However, the symptoms, eosinophilia and imaging findings deteriorated. We then performed a bronchoscopy, and bronchoalveolar lavage (BAL) fluid analysis revealed an increased percentage of eosinophils (82% of whole cells) as well as filamentous fungi. We first suspected that this was a case of allergic bronchopulmonary mycosis (ABPM) caused by Aspergillus infection and began corticosteroid therapy with an intravenous administration of voriconazole at POD 27. However, the fungal culture examination of the BAL fluid revealed mucormycetes, which were later identified as Cunninghamella bertholletiae by PCR and DNA sequencing. We then switched the antifungal agent to liposomal amphotericin B for the treatment of the pulmonary mucormycosis at POD 29. Despite replacing voriconazole with liposomal amphotericin B, the patient developed septic shock and died at POD 39. The autopsy revealed that filamentous fungi had invaded the lung, heart, thyroid glands, kidneys, and spleen, suggesting that disseminated mucormycosis had occurred. CONCLUSIONS: We describe the first reported case of pulmonary mucormycosis with pulmonary eosinophilia caused by Cunninghamella bertholletiae, which resulted in disseminated mucormycosis. Although it is a rather rare case, two important conclusions can be drawn: i) mycosis can simultaneously cause both invasive infection and a host allergic reaction, and ii) Cunninghamella bertholletiae rarely infects immunocompetent patients.

Tumor Lysis-like Syndrome in Eosinophilic Disease of the Lung: A Case Report and Review of the Literature.

Tumor lysis syndrome (TLS) is a metabolic disorder that is generally associated with a malignancy leading to hyperuricemia, hyperphosphatemia, and acute kidney injury. On the other hand, we sometimes encounter these phenomena in nonmalignant disease, which has been referred to as tumor lysis-like syndrome in some studies. We herein experienced a case in which tumor lysis-like syndrome occurred in the course of therapy for eosinophilic disease of the lung, a nonmalignant disease. Even in nonmalignant disease, massive cell lysis induced by therapy can cause phenomena such as TLS or tumor lysis-like syndrome.