*3.3. Clinical Characteristics*

Respiratory features of the disease included persistent cough, dyspnea, tachypnea, wheezing, occasional sputum production and rales. The peculiarity of pneumonia in these case series was the refractoriness of antibiotic treatments. Of note, in most cases, the additional administration of anti-inflammatory drugs probably might have resolved hypersensitivity pneumonia or idiopathic PH (IPH). The most commonly described systemic clinical manifestations were intermittent fever, progressive anorexia and FTT. Inflammatory markers were usually found to be high. Eosinophilia and severe iron deficiency anemia were frequently described at blood count examination. Gastrointestinal manifestations were reported in about half of the patients and included frequent vomiting or diarrhea. Rarely, lymph node hypertrophy with hepatomegaly, splenomegaly and hypertrophied tonsils or adenoids were labeled [7]. Noticeably, lymphonodular hyperplasia in biopsy was found in a child with HS-manifesting hematochezia [18].

Clinically, the disease can be complicated with cardiopulmonary involvement, such as alveolar hypoventilation, massive acute PH, pulmonary hypertension and *cor pulmonale*, or nephrological ones, such as crescentic glomerulonephritis [8,13]. These characteristics contributed drastically to morbidity and emerged in situations of overdue diagnosis and management. In particular, a delayed manifestation of the disease is episodic hemoptysis, which may represent a PH with repeated episodes of intra-alveolar bleeding, hemosiderin deposition in alveolar macrophages, followed by the development of pulmonary fibrosis and severe anemia [8]. PH may occur as a primary disease of the lung (also called IPH) or secondary to cardiac diseases, bleeding disorders, collagen-vascular diseases or systemic vasculitis. IPH, if not treated, leads to progressive pulmonary fibrosis and may be lethal [21].
