A 47-year-old female, known case of T2DM, with a past history of Pulmonary embolism. presented to the hospital with breathing difficulty MMRC Grade III-IV for one day.

No history of fever, cough, chest pain, palpitation, abdominal pain or vomiting. ON examination, she was conscious, oriented, tachypneic and tachycardic. No other significant examination findings. Her capillary blood glucose at presentation was 511 mg/dl and ABG showed severe High anion gap metabolic acidosis, her Urine ketone was positive and was diagnosed as diabetic ketoacidosis and was treated for the same. In the search for trigger for diabetic ketoacidosis and the patient complained of cough, we did a CT Chest- which revealed a Multifocal well defined thin-walled cysts of variable size with no Zonal predilection seen in both lungs with intervening normal lung parenchyma with the possible differential suggested as Brit hogg due syndrome and pan lobular emphysema. Her Pulmonary function test showed moderated restrictive pattern with low FEV1 and low FVC.

Pulmonologist opinion obtained for the same a was suggested to do mutation study and explained about the risk of pneumothorax in future and needs yearly Pulmonary function test.

Patients glycemic levels were closely monitored acidosis resolved, and was discharged.

Discussion

Cystic lung disease (CLD) comprises a group of conditions characterized by thin-walled parenchymal lucency (<2mm). The development of CLD often involves check-valve obstructions, observed in diseases such as fibrosis (FB), metastatic neoplasms, pneumatocele, lymphangioleiomyomatosis (LAM), and pulmonary Langerhans cell histiocytosis (PLCH). These obstructions can lead to distal over-inflation, contributing to the formation of cysts. Interestingly, cysts in LAM and PLCH exhibit a reduction in size during expiratory computed tomography (CT) scans, suggesting a degree of communication between these cystic lesions. Ischemia is another process implicated in lung cyst formation, as the obstruction of small capillaries supplying the terminal bronchioles can lead to airway necrosis and ischemic dilatation. Additionally, molecular mechanisms involving matrix metalloproteinase (MMP) and podoplanin (D2-40) have been suggested as contributors to lung tissue remodeling. Representative diseases that develop through these mechanisms include LAM, PLCH, and light chain deposit disease (LCDD).

1. Lymphangioleiomyomatosis (LAM): This multisystemic, progressive disorder primarily affects females of childbearing age, with a median onset age of 35. LAM can develop sporadically (S-LAM) or genetically in patients with tuberous sclerosis complex (TSC-LAM). TSC is an autosomal dominant trait characterized by benign hamartomatous lesions in various organs. LAM occurs in a substantial percentage of individuals with TSC, but the cystic changes specific to TSC-associated LAM are often asymptomatic in males. Both S-LAM and genetic LAM are associated with mutations in tumor suppressor genes, including TSC1 and TSC2. Mutations in these genes result in the abnormal activation of the mammalian target of the rapamycin (mTOR) signaling pathway, which regulates various cellular processes. Clinical presentations of LAM can range from asymptomatic to symptoms like dyspnea, cough, hemoptysis, recurrent pneumothoraces, chylous effusions, and respiratory failure. This variability in symptoms sometimes leads to misdiagnosis as conditions like asthma or chronic obstructive pulmonary disease (COPD). On high-resolution CT (HRCT), LAM cysts are typically round and small (usually 2 to 5 mm but occasionally as large as 30 mm), with no zonal predominance. Small centrilobular nodules are seen in TSC-LAM patients, corresponding to micronodular pneumocyte hyperplasia. A characteristic HRCT feature is the presence of more than 10 thin-walled, round cysts with preserved or increased lung volume. Additionally, lymphatic obstruction can lead to septal thickening or chylous effusion. Pathologically, LAM involves abnormal smooth muscle-like cells that proliferate, leading to cystic changes in the lungs and the development of angiomyolipomas in the kidney or liver. Although the origin of LAM cells is unknown, the pelvis, especially the uterus, is presumed to be the source due to the prevalence of axial lymphatic abnormalities in the pelvis. Moreover, LAM cells in the lung express estrogen and progesterone receptors. These cells may metastasize and recur in transplanted lungs, and like cancer cells, they rely on glycolysis for energy production, leading to the classification of LAM as a type of “perivascular epithelioid cell tumor” (PEComa).

2. Pulmonary Langerhans Cell Histiocytosis (PLCH): PLCH is another rare disease, predominantly identified in young adults, typically under 40 years of age. It is also observed in cigarette smokers, with no specific gender predilection. Clinical presentations of PLCH can range from being asymptomatic to causing symptoms such as shortness of breath, coughing, weight loss, fever, skin rash, and diabetes insipidus. High-resolution CT scans are valuable for diagnosing PLCH.

3. Lymphocytic Interstitial Pneumonia/Follicular Bronchiolitis (LIP/FB): LIP is an extremely rare disorder that involves the diffuse infiltration of the lung parenchyma by reactive lymphoid tissues. In contrast, FB is characterized by lymphoid follicular hyperplasia centered on the airway, vessels, and interlobular septa. Both conditions predominantly affect females between the ages of 40 and 70 years and often lead to respiratory symptoms like cough and progressive dyspnea.

4. Birt-Hogg-Dubé Syndrome (BHDS): BHDS is an autosomal dominant genodermatosis that usually manifests in the third decade of life. It is characterized by multiple fibrofolliculomas, trichodiscomas, and acrochordons. Patients with BHDS have an increased susceptibility to develop renal cell carcinoma, lung cysts, and spontaneous pneumothorax. A germline mutation of FLCN, which encodes the tumor suppressor folliculin, is responsible for BHDS and is located on chromosome 17p11.2. Treatment for BHDS skin lesions includes methods such as electrocautery, curettage, and laser ablation. Since folliculin has been implicated in the mTOR pathway, medications like rapamycin, an mTOR inhibitor, have theoretical applications in the treatment of Birt-Hogg-Dubé lesions.

Dr Vignesh A S
DNB General medicine Resident
Kauvery Hospital, Chennai

Dr. S. Sivaram Kannan
Clinical Lead & Chief Consultant Physician
Kauvery Hospital, Chennai