Journal of the Louisiana State Medical Society
ANSWER: plexiform arterial lesion (Grade IV) indicative of pulmonary hypertension
Sickle cell disease (SCD) is an autosomal recessive in- herited genetic disorder caused by a single point mutation in the gene for the B-globin chain of hemoglobin that results in chronic, severe hemolytic anemia. 5 It is one of the most common heritable hematologic diseases, with more than 200 million worldwide mutation carriers and nearly 1 in 600 African-Americans homozygous for the SCDmutation. 5 While themedian age of survival in SCDhas risen to roughly 45 years of age, lungmanifestations remain the leading cause of bothmorbidity andmortality, despite the fact they remain underdiagnosed by physicians. 6 Pulmonary complications in SCD vary widely and include acute chest syndrome, restrictive lung disease, thromboembolism, and PH. SCD as a cause of PH has gained only recent acceptance despite being initially described in 1936 by Yater and Hansman. 7 As a cause of PH, SCD is now recognized within the new clinical classification scheme, falling clearly into Group 5: PH with unclear multifactorial mechanisms, subgroup 5.1: those due to hematologic disorders such as chronic hemolytic anemia. 1 It is associatedwith impaired exertional tolerance, progressive heart failure, and a higher relative mortality largely due to right heart failure, thromboembolism, or cardiac arrhythmia. 6,8,9 Right heart catheterization remains the gold standard test for the diagnosis of PH, defined as a 1.1 Idiopathic, 1.2 Heritable [1.2.1 BMPR2, 1.2.2 ALK-1, ENG, SMAD9, CAV1, KCNK3, 1.2.3 Unknown Gene] 1.3 Drug- and Toxin-Induced, 1.4 Associated with [1.4.1 Connective tissue disease, 1.4.2 HIV, 1.4.3 Portal hypertension, 1.4.4 Congenital heart disease, 1.4.5 Schistosomiasis] 1’ Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis 1” Persistent PH of newborn (PPHN) 2.1 LV Systolic dysfunction, 2.2 LV Diastolic dysfunction, 2.3 Valvular disease, 2.4 Congenital/Acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies 3.1 COPD, 3.2 ILD, 3.3 Mixed restrictive/obstructive pattern disease, 3.4 Sleep disordered breathing, 3.5 Alveolar hypoventilation disorders, 3.6 Chronic exposure to high altitude, 3.7 Developmental lung disease
Pulmonary hypertension (PH) is a complex clinical diagnosis that has a variety of causes and encompasses multiple subtypes that, over the course of time, have been sub-classified, defined, and then reclassified again. Previ- ously subdivided into two main categories, the revised consensus schema now details five clinical groupings of disorders that cause PH. 1 An overview of these five clinical groupings can be seen in Table 1. The microscopic features ascribed to PH can broadly be called plexogenic arteriopathy (PA). 2 However, details regarding the spectrum of distinct histopathologic features have also been subject to a variety of grading systems that have undergone subsequent revi- sions and subdivisions. The more widely accepted schema for describing the histopathologic lesions of PAwas detailed by Katzenstein et al. 3 and yields six graded lesions (Grade I –VI), with each successive grade meant to reflect increasing severity of the clinical disease. A modified grading system for histologic lesions can be seen in Table 2. The Grade V lesion, otherwise known as the plexiform lesion, remains the pathologic hallmark of clinical PH, and a variety of hypotheses have been offered to explain its pathogenesis. 4
Table 1: Current Clinical Classification Scheme for Pulmonary Hypertension (PH) [adapted from Simmoneau et al.] 1 Clinical Group Number Major Category Subcategories Group 1
Pulmonary Arterial Hypertension (PAH)
Group 2
PH Due to Left Heart Disease
Group 3
PH Due to Lung Disease
Group 4
Chronic Thromboembolic PH (CTEPH) PH Due to Unclear Multifactorial Mechanisms
Group 5
5.1 Hematologic disorders: chronic hemolytic anemia, MPO disorders, splenectomy; 5.2 Systemic disorders: sarcoidosis, histiocytosis, lymphangioleiomyomatosis; 5.3 GSD, gaucher, thyroid disorders; 5.4 Other: tumoral obstruction, fibrosing mediastinitis, CRF, segmental PH
BMPR2 = bone morphogenic protein receptor type II, ALK-1; ENG = endoglin, SMAD9; CAV1 = caveolin-1; HIV = human immunodeficiency virus; LV = left ventricle; COPD = chronic obstructive pulmonary disease; ILD = interstitial lung disease; MPO = myeloproliferative; GSD = glycogen storage disease; CRF = chronic renal failure.
232 J La State Med Soc VOL 166 September/October 2014
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