November 2024 Medical Image of the Month: A Case of Short Telomeres

Figure 1. PA (A) and lateral (B) CXR demonstrating small lung volumes with peripheral reticulonodular opacities. The findings are highly suggestive of pulmonary fibrosis. To view Figure 1 in a separate, enlarged window click here.

Figure 2. Axial CT images from the upper (A), mid (B), and lower lungs (C). Images demonstrate a rather nonspecific pattern of fibrosis consisting of patchy areas of reticulation, ground glass, and septal line thickening. The findings are peripheral-predominant, but there was no predilection for the lung bases vs. apices. No subpleural honeycombing was seen. To view Figure 2 in a separate, enlarged window click here.

Figure 3. Results from telomere length testing of lymphocytes (A) and granulocytes (B). The results of both tests put the patient below the 10th percentile with the granulocyte telomere length being below the 1st percentile. To view Figure 3 in a separate, enlarged window click here.

A 50-year-old woman was referred to our institution for further evaluation of her ILD. Her history of present illness began during the COVID-19 pandemic, when she noticed that she had trouble climbing stairs while wearing a mask. She also had a slowly progressive cough which, at first, she attributed to seasonal allergies. Eventually her symptoms prompted pulmonary function testing at an outside institution, which showed moderately severe restriction with a DLco 40% of predicted. Chest x-ray (Figure 1) and chest CT (Figure 2) demonstrated findings of pulmonary fibrosis. The patient worked as an accountant and was a life-long nonsmoker. No concerning exposure history and no history of any medications associated with pulmonary fibrosis. Her family history is remarkable for a brother diagnosed with IPF at age 49, currently status post lung transplant. Her sister and father were both diagnosed with alpha-1-antitrypsin (both died in their 50’s). The patient also reports premature graying of her hair, at age 17. The combination of family history, gray hair, and pulmonary fibrosis prompted further testing for short telomeres, which was positive (Figure 3). The patient was diagnosed with interstitial lung disease secondary to short telomere syndrome.

Telomeres are short repeating nucleotides that the end of chromosomes that protect them from gradual degradation during aging (1). Short telomere syndromes (STSs) are accelerated-aging syndromes often caused by heritable gene mutations that result in decreased telomere length. Organ systems with increased cell turnover, such as skin, lungs, bone marrow, and GI tract, are most commonly affected (2). The relationship between telomere length and interstitial lung disease is complicated. The first association between genetically determined telomere abnormalities and lung fibrosis was observed for the telomeropathy dyskeratosis congenital (DC), an entity characterized by skin abnormalities, bone marrow failure, and pulmonary fibrosis, which was observed in 19% of patients (3). Mutations in other telomere related genes have subsequently been identified in familial and sporadic idiopathic interestitial pneumonias (4-6). Short telomeres have been identified in about 25 percent of sporadic cases of IPF (7) and should be suspected in patients with familial pulmonary fibrosis and/or early onset IPF in patients with signs of premature aging, such as developing gray hair at a young age.

Clinton E. Jokerst MD, Matthew T. Stib MD, Carlos A. Rojas MD, Michael B. Gotway MD

Department of Radiology

Mayo Clinic Arizona

Phoenix, AZ USA

References

1. Martínez P, Blasco MA. Telomere-driven diseases and telomere-targeting therapies. J Cell Biol. 2017 Apr 3;216(4):875-887. [CrossRef] [PubMed]
2. Mangaonkar AA, Patnaik MM. Short Telomere Syndromes in Clinical Practice: Bridging Bench and Bedside. Mayo Clin Proc. 2018 Jul;93(7):904-916. [CrossRef] [PubMed]
3. Knight S, Vulliamy T, Copplestone A, Gluckman E, Mason P, Dokal I. Dyskeratosis Congenita (DC) Registry: identification of new features of DC. Br J Haematol. 1998 Dec;103(4):990-6. [CrossRef] [PubMed]
4. Cronkhite JT, Xing C, Raghu G, Chin KM, Torres F, Rosenblatt RL, Garcia CK. Telomere shortening in familial and sporadic pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Oct 1;178(7):729-37. [CrossRef] [PubMed]
5. Diaz de Leon A, Cronkhite JT, Katzenstein AL, et al. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PLoS One. 2010 May 19;5(5):e10680. [CrossRef] [PubMed]
6. Newton CA, Batra K, Torrealba J, et al. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. Eur Respir J. 2016 Dec;48(6):1710-1720. [CrossRef] [PubMed]
7. Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007 Mar 29;356(13):1317-26. [CrossRef] [PubMed]

Cite as: Jokerst CE, Stib MT, Rojas CA, Gotway MB. November 2024 Medical Image of the Month: A Case of Short Telomeres. Southwest J Pulm Crit Care Sleep. 2024;29(5):45-47. doi: https://doi.org/10.13175/swjpccs049-24 PDF

November 2024 Imaging Case of the Month: A Recurring Issue

Michael B. Gotway MD

Department of Radiology

Mayo Clinic, Arizona

Phoenix, Arizona USA

Clinical History: A 65-year-old woman with a history of orthotopic liver transplantation 2 years earlier for non-alcoholic steatohepatitis presented to the Emergency Room for chronic fatigue, malaise, nausea and vomiting, and generalized weakness. She denies shortness of breath, hemoptysis, or productive cough. Her post liver transplant course was complicated by wound infection, biliary stricture requiring ERCP with stent placement, and Clostridium difficile colitis. Prior to her liver transplant the patient had chronic renal insufficiency which has been slowly progressing (creatinine of 2.8 mg/dL, estimated GFR of 17.6 mL) and she was currently undergoing renal transplant evaluation. The patient also has a past medical history of coronary artery disease requiring bypass grafting surgery, hypothyroidism requiring hormone replacement, and type II diabetes not requiring specific therapy. Her past surgical history included cholecystectomy and hysterectomy.

The patient is a lifelong non-smoker, she reports an allergy to penicillin and amoxicillin (hives), and she does not drink alcohol, and denies illicit drug use. Her medications include tacrolimus, mycophenolic acid, allopurinol, calcium, vitamin D, levothyroxine, pantoprazole, sertraline, fluconazole, sulfamethoxazole and trimethoprim, and prednisone.

On physical examination the patient was febrile (39.2º C). Her blood pressure was initially 97/53 mmHg; however, during her stay in the Emergency Department went as low as 71/41 mmHg. Her heart rate remained in the low to mid 90s, her respiratory rate was 12-14 breaths per minute, and her oxygen saturations were 99% on room air. The patient had uniformly decreased breath sounds bilaterally but the lungs were otherwise clear. Her cardiac examination was normal aside from trace bilateral pedal edema. Her abdominal examination was normal. She was neurologically intact.

A complete blood count showed a normal white blood cell count at 6.2 x 10⁹/L (normal, 3.4 – 9.6 x 10⁹/L), with a normal absolute neutrophil count of 3.65 x 10⁹/L (normal, 1.4 – 6.6 x 10⁹/L); the percent distribution of lymphocytes, monocytes, and eosinophils was normal. Her hemoglobin and hematocrit values were 10 gm/dL (normal, 13.2 – 16.6 gm/dL) and 33.7% (normal, 34.9 – 44.5%). The platelet count was normal at 134 x 10⁹/L (normal, 149 – 375 x 10⁹/L). The patient’s serum chemistries and liver function studies were normal, including an albumin level at 4.3 gm/dL (normal, 3.5 – 5 gm/dL), with normal alanine aminotransferase at 42 U/L (normal, 7-45 U/L) and aspartate aminotransferase of 40 U/L (normal, 8-43 U/L); alkaline phosphatase levels, bilirubin, and coagulation studies were normal. SARS-CoV-2 PCR testing was negative.

Frontal chest radiography (Figure 1) was performed.

Figure 1. Frontal (A) and lateral (B) chest radiography obtained in the Emergency Room. To view Figure 1 in a separate enlarged window, click here.

Which of the following statements regarding this chest radiograph is accurate? (Click on the correct answer to be directed to the second of twelve pages)

1. Frontal chest radiography shows unremarkable findings
2. Frontal chest radiography shows a moderate-to-large right pleural effusion
3. Frontal chest radiography shows mediastinal lymphadenopathy
4. Frontal chest radiography shows pneumothorax
5. Frontal chest radiography shows numerous small nodules

Cite as: Gotway MB. November 2024 Imaging Case of the Month: A Recurring Issue. Southwest J Pulm Crit Care Sleep. 2024;29(6):36-44. doi: https://doi.org/10.13175/swjpccs047-24 PDF