CME INDIA Case Presentation by Dr Nishith kumar, Pulmonologist, Ranchi.

CME INDIA Case Study:

23 yr. male with c/o Chronic Cough, Breathlessness & episodic streaking of blood in sputum

Do you know a disease with radiological – Finger in glove, toothpaste, tram-track or fleeting opacities?

23 yr. / Male with c/o Chronic Cough, Breathlessness & episodic streaking of blood in sputum since few years. H/O ATT intake in past. Multiple Sputum AFB & MTB CBNAAT- Negative.

This CXR was done on 24/11/20

E-22% N-47%

HRCT Thorax done (elsewhere) one year back for similar complaints.

What could be the DIAGNOSIS?

CME INDIA Discussion:

Dr Ranjeet Kumar, Ramgarh: Serum ACE level?

Dr Nishith Kumar: Not done

Dr S K Goenka, Begusarai: Appears Loculated eosinophilic pleural effusion. May be asbestosis, the cause behind it. Not sure, though.

Dr Nishith Kumar: No sir

Dr Noni G Singha, Dibrugarh: Hyper eosinophilic Pulmonary infarction

Dr H K Jha, Ranchi: Serum IgE?

Dr Nishith Kumar: 😃

Dr Ranjeet Kumar, Ramgarh: Eosinophilic granulomatosis with polyangiitis?

Dr Nishith Kumar: Clinical features & HRCT Thorax is hallmark of a disease entity that’s why didn’t do ANCA screening.

Dr Soma Shekhar, Mumbai: Eosinophilic granuloma

Dr Venkatesh Naik, Gulberga– Pulmonary Aspergilloma

Dr Sourav Maiti, Kolkata: Pulmonary Aspergillosis

Dr Kapil Sud, Delhi: Eoginophilic granuloma

Dr Akash Singh, Vadodara: Aspergilloma

Dr S K Sharwan, kalimpong: Aspergilloma

Dr Gaurabh Gupta, Delhi says: ABPA

Dr Nishith Kumar, Pulmonologist, Ranchi: FOR ABPA👏🏼👏🏼👏🏼👏🏼👏🏼👏🏼🙏🏽🙏🏽Do aspergillosis usually present with such opacity? – Asks Dr Ranjeet.

Basically, BA Like symptom. Fleeting opacities over time is characteristic feature of ABPA. These opacities usually appear and disappear in different areas of the lung over a period of time as transient pulmonary infiltrates. ABPA do present with such fleeting opacities sir or sometimes with HAM (high attenuation mucus). It’s worthwhile to note that ABPA is an allergic reaction rather than infection.

Patient was duly started on oral corticosteroid along with inhaled medications. Prednisolone 0.5 mg/kg/day for 1 month & then patient was advised to Follow up after 1 month.

Dated 08/01/2021

Did you use antifungal?

Dr Nishith Kumar: Usually Antifungal are not used as 1st line agent. They act as steroid sparing agents. Basically, they reduce airway Aspergillus burden. But yeah, as I was suspecting HAM, I prescribed Itraconazole 100mg BD along with oral corticosteroid.

Photomicrograph of Aspergillus fumigatus under lactophenol cotton blue mount

CME INDIA Learning Points

• Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus, manifesting with poorly controlled asthma, recurrent pulmonary infiltrates and bronchiectasis.
• The importance of recognizing ABPA relates to the improvement of patient symptoms, and delay in development or prevention of bronchiectasis, one manifestation of permanent lung damage in ABPA.
• In a genetically predisposed individual, inhaled conidia of A. fumigatus germinate into hyphae with release of antigens that activate the innate and adaptive immune responses (Th2 CD4+ T cell responses) of the lung.
• Primary therapy consists of oral corticosteroids to control exacerbations, itraconazole as a steroid-sparing agent and optimized asthma therapy
• Patients generally present with poorly controlled asthma, wheezing, haemoptysis and productive cough. Other symptoms include low grade fever, weight loss, malaise and fatigue. Expectoration of brownish black mucus plugs is seen in only 31–69% of patients. Patients can also be asymptomatic (albeit with asthma medications) and are diagnosed on routine investigations
• Total serum IgE levels. The serum total IgE level is a useful test in both diagnosis and follow-up of ABPA. A normal serum IgE (in the absence of systemic glucocorticoid therapy) generally excludes active ABPA as the cause of patient’s current symptoms. There is no consensus on the cut-off value of IgE level that should be used for diagnosis of ABPA, and the cut-off value remains speculative.
• Serum IgE antibodies specific to A. fumigatus :An elevated level of IgE antibodies specific to A. fumigatus is considered a characteristic finding of ABPA . The cut-off value of specific IgE against A. fumigatus in diagnosis of ABPA is not clear.
• Serum precipitins or specific IgG against A. fumigatus. Serum precipitins (IgG) against A. fumigatus are present in 69–90% of patients with ABPA but also in 10% of asthmatics with or without SAFS.
• Peripheral eosinophilia. A peripheral blood eosinophil count > 1000 cells/lL has been considered a major criterion for diagnosis of ABPA. However, a recent study found that only 40% of patients with ABPA presented with an eosinophil count > 1000 cells/lL at diagnosis .
• Culture of A. fumigatus in sputum is supportive but not diagnostic of ABPA because the fungus can also be grown in other pulmonary diseases due to ubiquitous nature of the fungi.
• Radiological manifestations of ABPA:
  • Chest X-ray has 50% sensitivity for the diagnosis of ABPA. It can show parenchymal infiltrate and bronchiectasis changes mostly in the upper lobes; however, all lobes may exhibit involvement.
  • HRCT Chest is the investigation of choice to detect bronchiectasis distribution and other abnormalities that are undetectable on a chest X-ray, such as centrilobular nodules and tree-in-bud appearance.
  • Patients of ABPA with no abnormalities on HRCT chest are labeled as serologic ABPA (ABPA-S).
  • Patients with central bronchiectasis on HRCT are labeled as ABPA Central Bronchiectasis (ABPA-CB).
• The diagnosis of ABPA is currently made on a combination of clinical, radiological and immunological findings using the Patterson criteria.
• The management of ABPA consists of anti-inflammatory therapy (systemic glucocorticoids) to suppress the immune activity, and use of antifungal agents to attenuate the fungal load in the airways.
• Oral corticosteroids are currently the treatment of choice for ABPA although there are no well-designed trials of steroids in ABPA. Glucocorticoids are anti-inflammatory and suppress immune hyperreactivity of both asthma and ABPA. There is no data to guide the dose and duration of glucocorticoids, and different regimens of glucocorticoids have been used
• Inhaled corticosteroids (ICS) Inhaled corticosteroids achieve high concentrations in the tracheobronchial tree with minimal systemic side-effects. Numerous small case studies have reported the use of ICS in ABPA
• Many patients also develop adverse effects related to chronic steroid therapy. The use of specific antifungal agents in ABPA can decrease the immune response by reducing the antigenic stimulus consequent to a decreased fungal burden, and can thus obviate/reduce the need for glucocorticoids. Ketoconazole has been used in ABPA, but has been replaced by the less toxic and more active agent, itraconazole.
• Newer antifungal drug: Voriconazole (300 to 600 mg/day) or posaconazole (800 mg/day) shows clinical improvement with a reduction in the requirement of oral glucocorticoids, improvement in asthma control, and decline in IgE levels. Cost is a major current limitation; however, the high rate of efficacy shows that treatment with these agents as second-line therapy is justified in specific patients.
• Omalizumab: An anti-IgE recombinant humanized monoclonal antibody which prevents binding of IgE to Fc-epsilon RI receptor on mast cells and basophils.It is mainly used to treat uncontrolled asthma on Step 4 GINA treatment guideline.

CME INDIA Tail Piece

Newly proposed diagnostic criteria for allergic bronchopulmonary aspergillosis.

Predisposing conditions Bronchial asthma, cystic fibrosis.

Criteria proposed by ISHAM working group:

Obligatory criteria (both should be present)

• Type I Aspergillus skin test positive (immediate cutaneous hypersensitivity to Aspergillus antigen) or elevated IgE levels against Aspergillus fumigatus
• Elevated total IgE levels (> 1000 IU/mL)

* Other criteria (at least two of three)

• Presence of precipitating or IgG antibodies against A. fumigatus in serum
• Radiographic pulmonary opacities consistent with ABPA† Total eosinophil count > 500 cells/lL in steroid na€ıve patients (may be historical)

 *If the patient meets all other criteria, an IgE value < 1000 IU/mL may be acceptable. † The chest radiographic features consistent with ABPA may be transient (i.e. consolidation, nodules, tram-track opacities, toothpaste/finger-in-glove opacities, fleeting opacities) or permanent (i.e. parallel line and ring shadows, bronchiectasis and pleuropulmonary fibrosis).

Rosenberg-Patterson criteria: It has eight major and three minor criteria

Clinical Pearls

• While investigating a patient with asthma for ABPA, it is recommended to perform an Aspergillus skin test and/or A. fumigatus specific IgE levels, with the latter being more sensitive .
• If either is positive, the total serum IgE levels should be measured.
• If the value is > 1000 IU/mL, other tests for ABPA including a CT of the chest, IgG specific to A. fumigatus or serum precipitins to A. fumigatus and total eosinophil count should then be performed to fully characterize the disease.

Shadows may present radiologically:

• ” opacity: suggestive of mucoid impaction in dilated bronchi.
• “Tramline shadows”: suggestive of parallel linear shadows extending from the hilum in bronchial distribution and reflecting longitudinal views of inflamed, edematous bronchi
• “Toothpaste shadows”: representing mucoid impaction of the bronchi
• “Ring shadows”: reflecting dilated bronchi with inflamed bronchial walls

Differential Diagnosis

• Corticosteroid-dependent asthma without ABPA
• Severe asthma with fungal sensitivity (SAFS)
• Cystic fibrosis (CF)
• Bronchiectasis
• Chronic necrotizing aspergillosis
• Chronic eosinophilic pneumonia
• Chronic obstructive pulmonary disease (COPD)
• Churg–Strauss syndrome
• Bronchocentric granulomatosis
• Acute eosinophilic pneumonia (including drug-induced pneumonitis)
• Pulmonary tuberculosis
• Parasitic infections
• Hypersensitivity pneumonitis

Source: R. Agarwal, A. Chakrabarti, A. Shah, D. Gupta, J. F. Meis, R. Guleria, R. Moss, D. W. Denning and For the ABPA complicating asthma ISHAM working group, Clinical & Experimental Allergy, 2013 (43) 850–873

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