Thinking Outside the Checkbox
The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient’s case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant.
© 2018 Society of Hospital Medicine
Despite the absence of uveitis and the negative pathergy test, his oral aphthosis, papulopustular rash, and large-vessel vasculitis make Behçet disease the likely diagnosis. Behçet disease is most strongly associated with HLA B51, although other HLA haplotypes (including HLA A26 and HLA B52) are frequent in Behçet disease as well. As aortitis and pulmonary vasculitis can be associated with substantial morbidity and mortality, an urgent consultation with a rheumatologist regarding the initiation of immunosuppression is warranted.
Based on the mucocutaneous lesions, radiologic findings consistent with large-vessel vasculitis, and positive HLA A26 and HLA B52, he was diagnosed with Behçet disease. After 1 week of treatment with prednisolone 60 mg daily, his cough resolved and the oral aphthous ulcers and papulopustular rash improved. One month later, a chest CT showed significant reduction of the wall thickening of the aorta, its branches, and of the left pulmonary artery. The nodular lesion in the left lower lobe was unchanged, but the ground-glass opacities in the left upper lobe had disappeared.
When prednisolone was tapered down to 17.5 mg, his dry cough and low-grade fevers recurred, along with a slight elevation of inflammatory markers, and a ground-glass opacity appeared on the periphery of the left upper lobe. A sputum culture and fungal antigens were negative. His cough improved with the resumption of the previous dose of prednisolone. He remained symptom-free after 2 years of treatment with azathioprine 150 mg daily and prednisolone 2 mg daily and is now only treated with azathioprine.
DISCUSSION
Behçet disease is a multisystem vasculitis involving blood vessels of all sizes in the arterial and venous circulation that presents with oral and genital ulcers, ocular abnormalities (uveitis, retinitis), skin lesions (erythema nodosum, nonfollicular papulopustular lesions, or “pseudofolliculitis”), pathergy, and vascular lesions (thrombophlebitis, thrombosis, and aneurysm).
This patient presented with a chronic cough from pulmonary involvement by Behçet disease. The most common presenting symptom in a study of 47 patients with Behçet disease with pulmonary arteriopathy was hemoptysis followed by a nonbloody cough.2 Among these patients with pulmonary artery aneurysm, thrombosis, or both, 40 (85%) had nodules caused by infarction or inflammation and 21 (45%) had ground-glass opacities attributed to intraparenchymal hemorrhage. There are several case reports of chronic cough attributed to large-vessel vasculitis.3-5 Although the pathology of vasculitis-related cough is not fully understood, the inflammation of large vessels (aorta and pulmonary arteries) adjacent to the tracheobronchial tree may irritate regional cough receptors.3
Disease classification criteria are common in rheumatologic diseases; these criteria are developed to categorize patients for research studies and are not intended to diagnose individual patients.6 The classification criteria favor increased specificity at the expense of sensitivity to avoid misclassifying patients as having a disease, which would compromise the results of research studies. For instance, a study assessing a treatment for Behçet disease must exclude patients with inflammatory bowel disease, as these distinct patient populations may demonstrate discrepant responses to the investigative therapy. The specificity and homogeneity favored by classification criteria make those criteria inappropriate to rely on exclusively for the diagnosis of individual patients.7 The symptoms of many autoimmune diseases develop sequentially over time. Waiting for a patient with active, multisystem vasculitis to fulfill all of the Behçet disease classification criteria can lead to the harmful withholding of disease-modifying treatment.
The diagnosis of Behçet disease is made on clinical grounds; there is no gold standard test or histopathologic finding, and classification criteria remain imperfect. Although classification criteria help clinicians understand cardinal disease features, they cannot substitute for the more complex clinical reasoning required to establish a working diagnosis. The clinician must understand the pretest probability of disease, consider the presence or absence of characteristic features, exclude competing diagnoses, and decipher the risk-to-benefit ratio of therapeutic options and the urgency of treatment when assigning a diagnostic label. This patient’s pneumonitis, mucocutaneous changes, aortopathy, and compatible HLA typing (coupled with the exclusion of infectious diseases) were sufficient to diagnose Behçet disease. This case reminds us that classification criteria serve as a starting point, not as an end point, and that clinicians must ultimately make diagnoses and initiate treatment by thinking outside the checkbox.
