Unilateral Dermatomal Cavernous Hemangiomatosis Responding to Dabigatran

Dear Editor, Acquired vascular anomalies are rare in adults but can lead to significant cosmetic and functional impairment. They are categorized as either vascular tumors or vascular malformations. Cavernous hemangiomas are a type of vascular malformation characterized by widely dilated vascular channels. Here, we present a case of acquired cavernous hemangiomas with a segmental distribution in a middle-aged female, successfully managed with dabigatran. A 42-year-old woman presented with a decade-long history of painful reddish lesions on the left upper trunk and back, extending to the left shoulder and proximal arm. The pain was aggravated by emotional stress and cold exposure, was radiating in nature and caused significant functional impairment of the left upper limb. Examination revealed multiple, tender, smooth, dome-shaped, reddish-purple papules (0.2-0.5 cm), surmounted on scattered pink to purple blanchable patches distributed primarily on the left side of the upper chest, shoulder, upper back, and left arm Figure 1. There was no associated pallor, epistaxis, hyperhidrosis, limb length or girth discrepancy, limb deformities, or any blood in stools. Systemic examination was within normal limits. The clinical differential diagnoses considered were angioleiomyomas, unilateral dermatomal cavernous hemangiomatosis (UDCH), glomangioma, glomuvenous malformation, and blue rubber bleb nevus syndrome (BRBNS).Figure 1: Multiple smooth reddish-purple papules (0.2-0.5 cm), on a background of mottled blanchable erythema on the left upper chest and armHemogram, liver and renal chemistries, coagulogram, and D-dimer were within normal limits. Ultrasound of the abdomen showed no adnexal or uterine masses. Magnetic resonance imaging revealed a moderate to slow-flow vascular malformation in the intraosseous and subfascial compartments of the left upper limb. Skin biopsy revealed numerous dilated vascular channels of varying caliber lined by bland endothelial cells in the dermis and subcutaneous tissue, with a mild perivascular inflammatory infiltrate suggestive of cavernous hemangioma Figure 2. Special stains for smooth muscle were negative. A final diagnosis of UDCH was offered.Figure 2: Histopathology revealed numerous dilated vascular channels of varying caliber lined by bland endothelial cells in the dermis with mild perivascular inflammatory infiltrate suggestive of cavernous hemangioma (Hematoxylin and eosin, 200×)In view of extensive disease associated with pain, and a recent report demonstrating a favorable outcome with the use of dabigatran in a patient with a vascular anomaly,1 the patient was started on dabigatran 150 mg twice daily along with nifedipine 10 mg once daily (discontinued after 2 months due to pedal edema). A baseline coagulation profile and renal function test were performed before initiation of dabigatran, which were within normal limits. The patient had a significant reduction in pain within 3 months of therapy. The repeat coagulation profile after 3 months of therapy showed mildly raised prothrombin time 22 seconds (0-21) and international normalized ratio 1.4 (1.0-1.3). Post 1-year treatment, there was complete resolution of pain and good improvement in erythema and the size of papular lesions Figure 3. The patient remains under follow-up on a once-daily dose of dabigatran 150 mg. We plan to continue dabigatran until a plateau of therapeutic response is seen.Figure 3: After 1 year of dabigatran treatment, there is a considerable reduction in background erythema, with a regression in the size and number of papules, which was associated with improvement in painCavernous hemangiomas present as soft, red or purple, compressible nodules or plaques, most commonly on the head and neck region. Cavernous hemangioma can affect any organ, with genetic factors (mutations in CCM1, CCM2, and CCM3 in cerebral cavernous malformations), radiation exposure, and hormonal factors being linked to its pathogenesis. Abnormal angiogenesis driven by vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) plays a role in its development and proliferation.2 UDCH is a rare congenital or acquired benign vascular anomaly characterized by unilateral segmental multiple hemangiomas in the lower dermis and subcutaneous tissue in the absence of any systemic disease or enchondromas.3,4 The term was initially coined by Wilkin, who reported a girl with multiple hemangiomas without any systemic disease, conferring a favorable prognosis.3 The term unilateral segmental cavernous hemangioma was used by Prasad et al.4 in their case for this condition. We believe this term is more suitable as lesions do not occupy the entire dermatome or a group of dermatomes. Histopathology shows dilated lobular vascular channels lined by a single layer of endothelium, with fibrous tissue in the deep dermis and subcutaneous tissue. There is a lack of literature regarding standardized and efficacious treatments for this disorder, with excision, sclerotherapy, and ablative procedures tried for localized disease. These options, including pulse dye laser, were not feasible in our case due to the extent of involvement. Drugs used for vascular anomalies, like sirolimus, do not have documented efficacy in cavernous hemangioma. Dabigatran has recently been found effective in a case of generalized essential telangiectasia (GET), where an incidental marked improvement was found in vascular lesions when it was administered for atrial fibrillation.1 Thrombin is a proangiogenic factor as it increases cell proliferation and upregulates angiogenic proteins. Thrombin potentiates the VEGF-induced angiogenesis by upregulating expression of VEGF receptors (kinase insert domain-containing receptor (KDR) and Fms-like Tyrosine Kinase-1 (Flt-1), increasing VEGF transcription and secretion via extracellular signal-regulated kinase 1/2 (ERK1/2) and activator protein 1 (AP-1/c-FOS) signaling pathways, increasing expression of VEGF in endothelial cells, and inducing hypoxia inducible factor 1-α (HIF-1α). Thrombin also stimulates the expression of other proangiogenic factors, including angiopietin-2 and platelet-derived growth factor (PDGF).5 Angiogenic factors, especially VEGF, have been demonstrated to play a role in the pathogenesis of both GET and cavernous hemangioma.3 Dabigatran, by directly inhibiting thrombin, would thereby lead to the inhibition of VEGF, PDGF, and angiopoietin-2-mediated angiogenesis, thus postulating its efficacy in the treatment of both these vascular anomalies. Dabigatran has shown a favorable long-term profile in conditions like atrial fibrillation, with no significant monitoring required.6,7 The response to dabigatran noted in our patient suggests the role of the thrombin pathway in vascular morphogenesis and proliferation. It explores the need for further research and the use of dabigatran in such patients, given the limited treatment options available. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest More than one authors are members of the editorial board of the journal. The manuscript was subject to journal’s standard procedure and peer review was held independently of the editor(s) or their research group(s). Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.