Adi Dagan, Pediatric Pulmonology The Edmond and Lili Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, affiliated to the Sackler Medical school, Tel-Aviv University, Israel.
Case report: 23 yrs old, medical student Recurrent hemopneumothorax Hx: Asymptomatic until age 19. No prior asthma or inhalation use. No prior pneumonia or lung disease. Non smoker. At 19 1 st hospitalization due to massive hemoptysis, non-traumatic.
1 st hospitalization One week prior, felt sharp pleuritic chest pain without fever or productive cough. Resolved for one week until this morning with sharp cough, bright red blood : 1/2 small cup: one episode. Otherwise feels well, no respiratory complaints.
DD - Hemoptysis Chest trauma Infectious Tuberculosis Rheumatologic Wegener s Bronchiectasis - Cystic fibrosis Pulmonary infarct Lung / pleural tumor Blood clotting defect Endometriosis - Catamenial Connective tissue disorder Iatrogenic post surgery / venous line Miscellaneous - Celiac
Investigation: Exam - Spo2 99% RA, pulse 80. No skin lesions of telangiectasia. Lungsdecreased breath sound on right base otherwise clear. Heart- no murmur. Extunremarkable. Blood- Hb 12.9 (410 abs eos), creat 0.9, INR 1.03, d-dimer 285, ANA, anti- DNA, anti-ro anti-la, c-anca neg, c3 c4 N
Chest X-Ray
HRCT
Imaging: CXR- large infiltrate in right lower lobe CT Chest (PE protocol) - large consolidation apical RLL surrounded by ground glass infiltrate. Multiple cystic lesions in LLL near pleura. Bronchoscopy no endobronchial lesion, neg. cultures (bacteria, fungal, mycobacteria)
Lung biopsy CT guided Subpleural blebs associated with fibrosis and reactive mesothelial hyperplasia, eosinophilic pleuritis, chronic alveolar hemorrhage, foci of pulmonary ossification No evidence of endometriosis, Langerhans cell histiocytosis or lymphangiomyomatosis on immunostains with CD1A, S-100 protein, HMB45, CD10 and SMA.
After discharge: Recurrent events - mild hemoptysis stained sputum, spontaneous resolution Few months post hospitalization: spontaneous lt. pneumothorax chest drain Working diagnosis Thoracic endometriosis w/ catamanial pneumothorax OCT treatment no improvement Recurrent PTX episodes bilaterally VATS pleurodesis mechanical abrasion, chemical - talcage, partial rt. pleurectomy / blebectomy
DD Pneumothorax: Primary spontaneous Asthma / COPD Alpha 1-antitrypsin deficiency A1AT - N Cystic fibrosis sweat test - N Pulmonary infection sequelae necrotizing pneumonia, septic emboli, tuberculosis Lymphangiomyomatosis LAM (+/- TS) PLCH pulmonary langerhans cell histiocytosis Birt-Hogg-Dube syndrome Connective tissue disease Marfan, EDS
Family history: Father 57 yrs, healthy, light smoker Mother 55 yrs, s/p rec. aneurysms splenic artery, renal arteries, s/p splenectomy (2005), s/p stent implantations, s/p breast ca, irradiation tx, s/p benign pituitary tumor resection, no known lung disease Brother 26 yrs old, severe scoliosis s/p operation
Patient history: Normal spontaneous pregnancy, PROM, vaginal delivery, term, 2700 gr Normal motor development, mild speech delay Umbilical hernia s/p repair, 1 yr old Recurrent otitis VT insertion, chronic perforation, ENT follow up Mild scoliosis physiotherapy tx Easy bruising recurrent hematomas Thinning hair and alopecia from age 20 Recurrent pillar cysts on scalp
Physical examination: Dysmorphism large deep-set eyes, pointed chin, thin lips, nose, mouth No clubbing, no tachypnea or dyspnea Skin dry, sensitive, translucent, lt. foot hematoma Hair thin, parietal cyst palpated no 2 nd infection Nose septal deviation Heart normal sounds no murmur Lungs poor air entry on rt, no wheeze or crackles Abdomen no organomegaly Limbs hyper-flexibility of small joints
Physical examination:
A diagnostic test was performed
Molecular blood test on the COL3A1 gene - heterozygous mutation exon 16. COL3A1 gene - chromosome 2q31 encodes the components of type III collagen, called pro-α1(iii) chains Type III collagen - skin, lungs, intestinal walls, and walls of blood vessels. Mutations in this gene cause the Ehlers Danlos syndrome type IV vascular type.
Review Ehlers-Danlos syndrome type IV Dominique P Germain Orphanet Journal of Rare Diseases (2007) Case report Spontaneous hemo-pneumothorax in a patient with Ehlers Danlos syndrome Rayees Ahmad Dar, Sabiya Hamid Wani, Majid Mushtaque, Reyaz Ahmad Kasana Gen Thorac Cardiovasc Surg (2012)
Ehlers Danlos syndrome (cutis hyperelastica)- Connective tissue disorders 6 types Abnormalities of collagen synthesis Skin and blood vessels - fragile, elastic, easily bruising, hypermobile joints with increased extensibility Frequency - 1 in 10,000 Genetics - autosomal dominant inheritance
Vascular-type EDS (type IV) Rare - 5-10% of EDS Diagnosis - Clinical criteria Skin biopsy - reduced type III collagen production by fibroblasts Genetics - molecular analysis of mutated COL3A1 gene VEDS - the worst prognosis of EDS
Diagnostic Criteria: Major : Thin, translucent skin Easy bruising Characteristic facial appearance (thin lips and philtrum, small chin, thin nose, large eyes) Arterial rupture Intestinal rupture Uterine rupture during pregnancy Family history, sudden death in close relative
Diagnostic Criteria: Minor : Acrogeria (aged appearance to extremities) A-V carotid-cavernous sinus fistula Hypermobility of small joints Tendon / muscle rupture Varicose veins Pneumothorax / pneumohemothorax Joint subluxations / dislocations Congenital dislocation of hips Talipes equinovarus (clubfoot) Gingival recession
Complications: Vascular complications (65%) - all anatomical areas usually large and medium arteries, such as abdominal Dissections of vertebral arteries and carotids (carotid-cavernous fistulae) - typical Recurrent colonic perforations (30.1%) Pregnancy increases risk of uterine or vascular rupture and sudden death Complications - 25% before 20 years of age and 80% by the age of 40 Median age of death - 50 years
Respiratory manifestations: Type I and III collagen - major collagens in lungs Type III collagen amount in lungs with VEDS - lower Vulnerable to lacerate hematoma - organization Not common complications (<5%): include recurrent hemoptysis, bulla and bleb formation, and spontaneous pneumothoraces
Management: No specific treatment Genetic consultation - know associated risks Symptomatic treatment / prophylactic measures Arterial, digestive or uterine complications require immediate hospitalization in ICU Invasive imaging techniques - contraindicated Conservative approach - recommended Surgery may be required urgently for potentially fatal complications