PULMONARY hemangiomatosis is a rare, fatal disorder characterized by diffuse microvascular proliferation within the lung. The disease most often affects children and young adults and usually progresses rapidly, causing death from pulmonary hypertension or bleeding. Most cases have been diagnosed at autopsy. Corticosteroids and cyclophosphamide have been used for this condition, but no successful therapy has been described. We describe a patient with pulmonary hemangiomatosis who presented with digital clubbing and bilateral interstitial pulmonary disease. After a decline in the patient's exercise tolerance, therapy with interferon alfa-2a was initiated and has been continued for 14 months at the time of . . .

Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a.

Hemangiomas of infancy are unique, benign, pediatric tumors of endothelial cells characterized by an initial phase of rapid proliferation, followed by slow involution, often leading to complete regression. Although most of these tumors are small and innocuous, some may be may be life- or function-threatening, or have associated structural congenital anomalies. Uncertainties regarding their diagnosis or management often prompt referral to a dermatologist. The pathogenesis of hemangiomas of infancy is not well understood, but recent findings suggest a unique vascular phenotype with dysregulated vascular homeostasis. This article reviews new information regarding the pathogenesis of these tumors and highlights the more worrisome presentations, including syndromic hemangiomas, that are likely to be problematic. In addition, management strategies and treatment options are discussed. (J Am Acad Dermatol 2003;48:477-93.) Learning objective: At the completion of this learning activity, participants should be able to describe the clinical features of hemangiomas of infancy and potential complications as well as to understand the strengths and limitations of various treatment options.

Hemangiomas of infancy

Two cases of hereditary hemorrhagic telangiectasia (HHT) with neurological involvement are presented. One patient had multiple vascular malformations including telangiectasias of the brain, medulla, and spinal cord and a berry aneurysm of the internal carotid artery; she also had a large cerebellar abscess, presumably reflecting the presence of a pulmonary arteriovenous fistula. The second patient had an idiopathic subarachnoid hemorrhage. In more than 200 reported patients with HHT involving the nervous system, 61% had lesions seondary to a pulmonary arteriovenous fistula (cerebral hypoxemia, paradoxical and septic emboli, and brain abscess). The findings emphasize the need for early surgical correction of such fistulas. In 36% of the patients with neurological involvement and HHT, vascular malformations of the brain and spinal cord were documented, and in 3%, portal-systemic encephalopathy was noted. Multiple lesions were frequent. HHT should be considered a generalized vascular dysplasia (universal or systemic angiomatosis), and not simply a benign mucocutaneous disease.

Neurological manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): report of 2 cases and review of the literature

Vascular malformations of the central nervous system (C.N.S.) are classified by size, location, and morphologic type, distinguishing a) capillary telangiectasias, b) cavernous malformations, c) venous angiomas, d) arteriovenous malformations (AVMs) including varix of the great vein of Galen, and other vascular malformations (e.g. Sturge-Weber syndrome). The morphology and predominant location pattern of the different types of vascular malformations in the brain and spinal cord, and their embryology are reviewed. In the brain and its coverings, all types mainly AVMs and venous angiomas do occur, representing 5–9% of all intracranial space-occupying lesions and 20–40% of the sources of surgically treated intracranial hemorrhages. 50–80% of the angiomas are located in the cerebral hemispheres, 10–18% in central brain areas (basal ganglia, internal capsule, choroid plexus), and 10–30% in the posterior fossa. The major types of cerebral vascular malformations are described with reference to their anatomical features, location, chief arterial and venous supply, and prominent complications. Spinal vascular malformations, accounting for 3 to 12% of spinal space-occupying lesions, include vertebral, extradural, dural, subpial and intramedullary angiomas which occur as isolated or complex vascular anomalies and may involve various covering layers at the same level. The preferential occurrence of angiomas on the dorsal surface of the cord and in the caudal regions is related to the embryologic development of spinal vasculature. Frequent association of spinal angiomas (20–25%) with other vascular anomalies and dysplasias emphasizes their hamartomatous nature and developmental origin. Spinal angiomas include a) capillary telangiectasias with extra- or intradural and, rarely, intramedullary location, b) cavernomas, mainly arising in vertebral bodies, c) venous angiomas, mainly located in vertebral bodies and in the extradural space, and c) AVMs constituting the commonest type, that may affect both the pial and radicular vessels and can penetrate into the cord. They present as simple AV fistulas, cirsoid angiomas with localized vascular plexuses and large complex convolutions (“juvenile” type). The complications of spinal angiomas include subarachnoid hemorrhage, rare epidural hematoma, hematomyelia, compression lesions of the cord and roots, and ischemic changes causing chronic progressive radiculomyelopathy, previously referred to as Foix-Alajouanine syndrome. Chronic damage to the cord and spinal roots results from pressure effects, thrombosis of the abnormal vessels, disorders of venous drainage, and „steal“ phenomena related to the vascular anomalies.

Vascular malformations of the central nervous system: a morphological overview.

Naevi and Other Developmental Defects

Two infants with diffuse neonatal hemangiomatosis are presented. One infant developed thrombocytopenia and bleeding while the other infant with more widely diffuse lesions succumbed to extensive central nervous system involvement. Steroid therapy caused no obvious alteration in either of the patient9s course. The vascular lesion in this disease is possibly congenital absence of vessel wall pericytes. Six previous cases of diffuse neonatal hemangiomatosis are briefly reviewed in relation to the sites of the lesions, cause of death and malignant potential.

Diffuse neonatal hemangiomatosis

The typical clinical features of uremic medullary cystic disease—anemia, polyuria, polydypsia, and uremia—were observed in three young siblings (the typical setting of familial juvenile nephronophthisis). Renal juxtemedullary cysts were found at autopsy in one sibling, confirming the concept that these two diseases are truly rehated. The mother of the siblings studied in this paper demonstrated an inability to concentrate urine.

Fred Alexander

Papers

Diffuse neonatal hemangiomatosis

Familial uremic medullary cystic disease