Sylvia Worthy

Small airway diseases

High-resolution CT scan is currently the best imaging technique for assessment of diseases of the bronchioles. This article describes the anatomic basis for the findings. This is followed by a presentation of the findings in bronchiolitis, as it is currently classified, into five main groups: (1) cellular bronchiolitis, (2) panbronchiolitis, (3) respiratory bronchiolitis, (4) constrictive bronchiolitis, and (5) bronchiolitis obliterans with intraluminal polyps.

The appearance on MRI of vertebrae in acute compression of the spinal cord due to metastases

We studied MR images of the spine in a consecutive series of 100 patients with acute compression of the spinal cord due to metastases. All patients had documented neurological deficit and histologically proven carcinoma. MRI was used to localise bony metastatic involvement and soft-tissue impingement of the cord. A systematic method of documenting metastatic involvement is described. A total of 43 patients had compression at multiple levels; 160 vertebral levels were studied. In 120 vertebrae (75%), anterior, lateral and posterior bony elements were involved. Soft-tissue impingement of the spinal cord often involved more than one quadrant of its circumference. In 69 vertebrae (43%) there was concomitant anterior and posterior compression. Isolated involvement of a vertebral body was observed in only six vertebrae (3.8%). We have shown that in most cases of acute compression of the spinal cord due to metastases there is coexisting involvement of both anterior and posterior structures.

Lack of association between KIR and HLA-C type and susceptibility to idiopathic bronchiectasis

INTRODUCTION Idiopathic bronchiectasis is a poorly defined disease characterised by persistent inflammation, infection and progressive lung damage. Natural killer (NK) cells provide a major defense against infection, through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIR), and human leukocyte antigens (HLA) class I molecules. Homozygosity for HLA-C has been shown in a single study to confer increased genetic susceptibility to idiopathic bronchiectasis. We aimed to assess whether the KIR and HLA repertoire, alone or in combination, may influence the risk of developing idiopathic bronchiectasis, in an independent replication study. METHODS In this prospective, observational, case-control association study, 79 idiopathic bronchiectasis patients diagnosed following extensive aetiological investigation were compared with 98 anonymous, healthy, age, sex and ethnically-matched controls attending blood donor sessions in the same geographical location. DNA extraction was performed according to standardised techniques. Determination of presence or absence of KIR genes was performed by a sequence specific oligonucleotide probe method. Allele frequencies for the proposed KIR, HLA-B and HLA-C risk alleles both individually and in combinations were compared. RESULTS We found no significant differences in allele frequency between the idiopathic bronchiectasis and control samples, whether considering HLA-C group homozygosity alone or in combination with the KIR type. DISCUSSION Our results do not show an association between HLA-C and KIR and therefore do not confirm previous positive findings. This may be explained by the lower frequency of HLA-C1 group homozygosity in the control population of the previous study (27.2%), compared to 42.3% in our study, which is consistent with the genetic profiling of control groups across the UK. The previous positive association study may therefore have been driven by an anomalous control group. Further larger prospective multicentre replication studies are needed to determine if an association exists.

Inherited pulmonary cylindromas: Extending the phenotype of CYLD mutation carriers

Germline mutations in the tumour suppressor gene CYLD are recognized to be associated with the development of multiple cutaneous cylindromas. We encountered such a patient who presented with breathlessness because of multiple pulmonary cylindromas.

Blood in a chest drain

A 21-year-old male with Ehlers-Danlos type IV (EDS IV) presented to the emergency department with sudden onset right-sided pleuritic chest pain. On examination, some of the typical features of EDS IV including large eyes and small chin were noted, although other features such as sunken cheeks, thin nose and lips, and lobeless ears were not noted [1]. His respiratory rate was 20 breaths·min−1, saturations were 93% on air increasing to 98% on 28% oxygen via a venturi mask. Pulse was 115 beats·min−1 in sinus rhythm and his blood pressure was 112 over 64 mmHg. There was decreased air entry in the right hemithorax, with decreased vocal resonance. The trachea was central and there was no surgical emphysema. ### Task 1 1. What is the best description of the chest radiograph (fig. 1)? Figure 1 Chest radiograph on admission. 1. A right-sided tension hydro-pneumothorax 2. A right-sided hydro-pneumothorax 3. A right-sided cavitatory pneumonia 4. A right-sided pneumo-peritoneum 2. What would the next therapeutic step be? 1. Simple observation and high flow oxygen 2. Aspiration of pneumothorax 3. Insertion of a small 12-French bore Seldinger chest drain 4. Insertion of a large-bore chest drain ### Answer 1 The chest radiograph shows a right-sided hydro-pneumothorax and the next therapeutic step would be insertion of a small 12-French bore Seldinger chest drain. Local anaesthetic was instilled into the second intercostal space and it was possible to aspirate air via the green needle. A 12 French intercostal drain was inserted using the Seldinger technique with no immediate complications and connected to an underwater seal bottle which …

Tracking tumor kinetics in patients with germline CYLD mutations

REFERENCES 1. Mitrovic S, Fautrel B. New markers for adult-onset Still’s disease. Joint Bone Spine. 2018;85(3):285-293. 2. Narvaez Garcia FJ, Pascual M, Lopez de Recalde M, et al. Adult-onset Still’s disease with atypical cutaneous manifestations. Medicine (Baltimore). 2017;96(11):e6318. 3. Gerfaud-Valentin M, Jamilloux Y, Iwaz J, et al. Adult-onset Still’s disease. Autoimmun Rev. 2014;13(7):708-722. 4. Bilgic H, Ytterberg SR, Amin S, et al. Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum. 2009;60(11):3436-3446. 5. Lee JY, Hsu CK, Liu MF, et al. Evanescent and persistent pruritic eruptions of adult-onset Still disease: a clinical and pathologic study of 36 patients. Semin Arthritis Rheum. 2012;42(3): 317-326.

Inherited pulmonary cylindromas

CYLD cutaneous syndrome (CCS) is a rare inherited skin disease. This disease affects about 1 in every 100,000 people in the U.K. and is more severe in females. It causes the development of multiple, sometimes hundreds, of skin tumours in each patient; these skin tumours, called cylindromas, can be painful and may grow rapidly. Depending on where they grow they can also cause problems; for example, blockage of the ear canal affecting hearing, and pubic tumours causing sexual dysfunction. We showed for the first time, evidence of cylindromas in the lung in a mother and daughter with CCS. Samples of both patients’ lung and skin tumours were taken, and studied with pathologists, and investigated with cutting‐edge genetic tests. These genetic tests allowed us to demonstrate that the gene signature of the lung cylindromas were similar to the gene signature of skin cylindromas. This suggests that sometimes, cylindroma cells may travel from the skin to the lung. It is important that doctors looking after CCS patients are aware of this possibility and understand the need to investigate if patients with this condition present with new symptoms of lung disease. It also guides doctors regarding follow‐up with repeat scans for these patients and treatments such as laser to trim back these lung tumours if they are going to block the large airways in the lung.

Tracking tumour kinetics in patients with germline CYLD mutations

BG01 Lessons learnt from the design and development of a multicentre rare genetic skin disease research study S. Tso, J. Simpson, M. Martinez-Queipo, E. Glass and J. McGrath St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, London, U.K. and St John’s Institute of Dermatology, King’s College London, London, U.K. We recently established a multicentre research project aimed at finding the genotype–phenotype correlations for a group of rare genetic skin disease called autosomal recessive congenital ichthyosis. Twelve research sites are involved to date. This is the second dermatology-themed portfolio study to have utilized the 2013 National Institute for Health Research U.K.’s Rare Genetic Disease Research Consortium Agreement (Musketeer’s Memorandum). We would like to share our experiences in the design and development of our project, which would be educational to trainees and helpful to investigators who are interested in taking up rare disease research. A rare disease is defined by the European Union as one that affects less than five in 10 000 of the general population. We have encountered two key challenges in the design and development of our project: (i) patient identification and participation and (ii) site coordination. There is no national patient register for the group of rare genetic skin disease we are investigating, which has a prevalence of up to one in 128 000 of the population. It is challenging to motivate potential participants to travel long distances to see the project team at the chief investigator’s (CI) research site. We addressed these challenges via (i) the establishment of a national working group of clinicians with a special interest in genodermatoses to raise awareness about the study and to gauge potential patient numbers from different sites (this has informed our strategy on where and when to expand the research study); (ii) involvement of a patient support group in the project design and development process and keeping the support group up to date about our work; (iii) utilization of the Musketeer’s Memorandum, enabling us to expand rapidly the number of research sites in a short period of time; (iv) making provisions in the study protocol to permit remote recruitment of potential participants by methods such as post or telephone, and to permit inclusion of deceased patients into our study with next-of-kin consent; and (v) supporting local principle investigators (PIs) using available Clinical Research Network assets and to deploy the CI team to support local PIs remotely or in person, depending on the level of support required. It is crucial that the CI’s team takes the time to listen, learn and understand how each individual site operates so that tailored support can be provided to each PI.

A not so simple effusion.

We describe the case of a patient with an empyema, how it forms and what the evidence behind the treatment options are with specific reference to intrapleural thrombolytic therapy.

Black lungs and tuberculosis

A never-smoking 82-year-old woman with a past medical history of type-2 diabetes presented to the outpatient clinic with a 3–4 months history of purulent bronchitis, haemoptysis, weight loss and fevers. She had lived in a small village in India and Pakistan all her life and had been visiting the UK intermittently until setting up permanent residency a few months ago. She denied any history of tuberculosis or any previous recent contacts. Clinically, she had no lymphadenopathy and had bilateral crackles in the upper zones on auscultation. Her oxygen saturations were 98% on air. Figure 1 Chest radiograph ### Task 1 Interpret the chest radiograph (fig. 1) Answer 1. The chest radiograph shows generalised nodularity with left upper lobe collapse and right middle lobe collapse. Crowding of the left upper ribs suggests long-standing volume loss. A diagnosis of tuberculosis was entertained and sputum sent for analysis. A helical CT scan was also performed. Figure 2 Computerised tomography images ### Task 2 Please interpret her CT scans (fig. 2) Answer 2. There is right middle lobe collapse with fluid-filled distal bronchi and patent origin of bronchus. There is marked volume loss and scarring in left upper lobe with fluid-filled bronchi and distorted left upper lobe bronchus, but also a larger low attenuation area on the left peri-hilar region. There are also numerous mainly peri-bronchovascular nodules in both lungs. There is also reduced lung attenuation in …