Vanishing lung Vanishing presentation

Lea Bentur, MD

Pediatric Pulmonary Institute

Ruth Rappaport Children's Hospital

Oct 2012

• 40 days old girl

• Normal pregnancy (38wks) & delivery (2,900Kg)

• Muslims, no-consanguinity, 2 healthy brothers

• Congenital papular-vesicular- pustular rash

• Infectious were ruled out

• Skin biopsy was performed(Dr Nael Elias)

At the age of 40 daysRappaport

• Significant rash

• Hepatosplenomegaly, lymphadenopathy

• Pancytopenia

• Skin biopsy– Langerhans cell histiocytosis (LCH)

• Bone marrow aspiration –N

• Skeletal survey- N

• Cardiac Echo –small PDA, PFO

• Treatment-corticosteroids+ vinblastine+6-MP

2 days later..

• Acute respiratory failure

• Intubation & ventilation, high pressure

• Surfactant administration-limited improvement

• HFOV, NO , inhalations , steroids, Mg, antibiotics

CXR- admission

2 days 7 days 8 days

Recurrent pneumothorax

CT-vanishing lungs

Holub was a Czech poet -immunologist, and his experience treating and observing illnesses is the basis for this amazing book.

Vanishing lung diseases-rapid bulla formation Infants

• Pneumatoceles (post infectious:PostStaphylococcus)

(Post measles pneumonia)

(Post H1N1)

• Neonatal bilateral emphysema (Cong. Marfan’s)

• Infantile LCH

Adults

• Lymphangioleiomyomatosis (mostly female)

• Isolated pulmonary LCH (smokers)

• Cannabis smoking (adults)

• R/O Bilateral pneumothoraces

Vanishing lung can you help ?

• Rapidly vanishing lung disease by LCH

• Respiratory failure

• Recurrent pneumothoraces

Cysts resections?

Endobronchial fibrin glue?

Pleurodesis?

Wait for restoration of lung parenchyma?

Future Lung transplant?

Langerhans cell histiocytosis (LCH)Letterer Siwe, Hand-Schüler-Christian ,Eosinophilic granuloma

• Rare ;1-10 of 1,000,000 children <18 years

• Extremely heterogeneous clinical spectrum

• Single organ/Multisystem (MS-LCH)

• Primary pulmonary is rare in children

• Early age at diagnosis+ MS-LCH (liver, spleen, hematopoietic system)- poor prognosis

• Lung involvement was not independent prognostic factor ( 25 yrs, Europe,102 children)

(J Pediatr 2012;161:129-33)

LCH Pediatr Blood Cancer 2004;42:398–411

• Pathophysiology -poorly understood.

• Histiocyts -dendritic cells of BM marrow origin serve as antigen presenting cells

• Previously considered benign, reactive,

immunologically mediated process

• Recently, mutations in mitogen activated protein kinase (MAPK) pathway, BRAF-V600E in cancer-redefinition as neoplasm (Pediatr Blood Cancer 2016;00:1–9)

• LCH may infiltrate any tissue

• The infiltration is accompanied by chronic inflammation and the formation of granulomas.

Langerhans cells (straight arrows), characterized by a moderate amount of eosinophilic cytoplasm, elongated kidney-shaped nuclei, and a nuclear groove (curved arrows).

EM-Birbeck bodies the zipperlike central core and bulbous structure at one end resembling a tennis racket

Staining with antibodies to CD1a, a glycoprotein antigen at the cellular surface(brown-stained areas).

S100 protein -a useful but not specific indicator of histiocytic disorders

Course

• Spontaneous regression of solitary lesions may occur.

• Multifocal disease –a chronic low-level course

or rapidly persistent organ dysfunction.

• Fatal outcomes often in children younger than 2 years) with multisystem involvement.

Treatment (orphan dis)

• Treatment approaches remain empirical, and the response to treatment is unpredictable

• Aggressive therapy in MS-LCH consisting of multi-agent immunosuppressive/chemotherapy

• Two years protocol

• BMT in refractory disease

• A high recurrence rate

Pulmonary involvement

• In 23%–50% with MS- LCH

• <10% of children with a solitary site

• Symptoms + confirmed LCH

• Typical radiology + confirmed LCH

• PFT’s are usually not feasible

• BAL with > 5% CD1a-positive cells

• Histopathological verification is not required

J Pediatr 1996;129:913–915Semin Respir Crit Care Med. 2007 ;28:514-24

Typical radiology

• Reticulonodular pattern, multiple nodules

• Bizarrely shaped cystic lesions

• Mainly upper & middle lobes

• Spontaneous pneumothorax

• LCH lung volumes usually normal or increased

• CT- informative

• Positive PET

Pulmonary involvement-Acute

• Rapid proliferation of LC almost exclusively in the bronchial and bronchiolar epithelium.

• Formation of destructive granulomas adjacent to the small airways.

• Cavitation of these granulomatous nodules lead air trapping, airway obstruction and formation of bizarrely shaped cystic lesions with varied wall thicknesses and sizes

RadioGraphics 2004;24:821–841.

• The chronic stage is characterized by fibrosis (scars and surrounding cystic spaces of variable diameter) and traction emphysema.

• Restrictive and obstructive impairment

• Pulmonary hypertension from extensive parenchymal destruction.

Pulmonary involvement-Chronic

Vanishing lung can you help ?

Cysts resections?

Endobronchial fibrin glue?

Pleurodesis?

Wait for restoration of lung parenchyma? case

Future Lung transplant? 6 months 2.8 years

Med Pediatr Oncol. 2000;35:438-42 J Pediatr. 2016Jan

succumbed at 21mon

months 56Since then-• Corticosteroids+ vinblastine+6-MP (2 years)

• Almost always ventilated, vapotherm, oxygen

• Tracheostomy +Gastrostomy +Fundoplication

• Pneumothoraces requiring resuscitation (resolved)

• Multiple bronchoscopies

• PHT- mild to moderate (viagra until June 2016)

• On–off PICU :episodes of sepsis/respiratory failure

• Hemoptysis –Embolization (twice) of Rt bronchial arteries

• No evidence of active LCH

• No rash, no pancytopenia

• Normal liver biopsy

• No skeletal involvement

• No diabetes insipidus

• But chronic obstructive respiratory failure

• Since 01/2015 home ventilation

Age 1 year

15 months

18 months

05/2015

2015-2016

• 24 –h Home ventilation since 01/2015 (Dr Elias)

• 10/2015-Bleeding from tracheostomy

• Significant developmental delay-Neurodegenerative Syndrome?

(PLOS ONE July 15, 2015)

06/2016

Vanishing lung can you help ?

• Cysts resections? Mistake? (non reported)

• Endobronchial fibrin glue? Mistake? (non reported)

Enlarging pneumatocele in a neonate by fibrin sealant injection via pigtail catheter Pediatr Pulmonol. 2016 Feb;51(2):E5-7.

• Pleurodesis? Mistake? (one case in LCH-failed)

• Wait for restoration of lung parenchyma?