News on infantile haemangioma. Part 1: clinical course and pathomechanism.

Currently, there is no doubt that the first choice of treatment for alarming infantile haemangiomas (IHs) is oral beta-blockers. However, research in this field remains active, as the pathogenesis of IH is still not completely elucidated. Furthermore, there are different approaches to the management of IHs with beta-blockers. In Part 1 of this review we will discuss the state-of-the-art evidence for IH with regard to (i) the definition, epidemiology, course, risk factors and sequelae, and (ii) the pathogenesis, focusing on genetic studies. This review will update the reader on the latest developments in the pathogenesis of IH. Furthermore, we hope this review will give more insight into risk factors and sequelae of IH, thereby contributing to better decisions in the clinical management of patients with IH. The therapy and evaluation of IHs will be discussed in Part 2 of this review.

Von Hippel-Lindau Syndrome Phenotype With Prominent Vitreoretinal Neovascularization Treated With Early PPV: A Case Series and Literature Review.

BACKGROUND AND OBJECTIVE: To describe a case series of three patients in one family with Von Hippel-Lindau (VHL) disease who presented with vitreoretinal neovascularization and resulting tractional retinal detachments (TRDs). This vitreoretinal phenotype of VHL may benefit from early surgical intervention. PATIENTS AND METHODS: Descriptive case series of three patients in one family with VHL disease. A review of the literature regarding surgical intervention for VHL was performed. RESULTS: All three patients developed prominent intravitreal neovascularization with fibrovascular growth within the vitreous secondary to a retinal capillary hemangioma. Two subjects with intravitreal neovascularization were treated with laser and cryotherapy but eventually developed a TRD. The final vision in these two patients was light perception and 20/300. The eye that was preemptively treated with vitrectomy to remove the vitreous sustaining the neovascularization had visual acuity of 20/50 after surgery. CONCLUSION: Intravitreal neovascularization with fibrovascular proliferation may be an indication for vitrectomy prior to the development of retinal detachment. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:109-115.].

INTRAVITREAL INJECTION OF PROPRANOLOL FOR THE TREATMENT OF RETINAL CAPILLARY HEMANGIOMA IN A CASE OF VON HIPPEL-LINDAU.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intravitreal propranolol for the management of retinal capillary hemangioma in a patient with Von Hippel-Lindau. METHODS: Two intravitreal injections of 50 µg/0.05 mL propranolol were administered 6 weeks apart in the left eye of a 26-year-old patient with bilateral multiple retinal capillary hemangiomas. Safety and response to therapy were evaluated using electroretinogram, fluorescein angiography, and measurement of visual acuity. Laser photocoagulation was performed in the right eye. RESULTS: One month after the second intravitreal injection of propranolol, fluorescein leakage decreased from the tumors located on the optic nerve head and in the inferonasal retinal periphery. Reduction of the retinal capillary hemangioma vascularity and enhancement of its fibrosis associated with the attenuation of the feeder vessel were also observed. Ophthalmic examination showed no adverse effect except for a mild transient vitreous haziness after each injection. Electroretinogram performed 4 weeks after the first injection revealed no retinal toxicity. CONCLUSION: Intravitreal propranolol showed a therapeutic effect on retinal capillary hemangioma with no short-term adverse effects except a mild transient inflammatory response in a patient with Von Hippel-Lindau.

Salvage therapy of reactive capillary hemangiomas: Apatinib alleviates the unique adverse events induced by camrelizumab in non-small cell lung cancer.

BACKGROUND: Camrelizumab is a promising anti-programmed cell death-1 agent for non-small cell lung cancer (NSCLC) and induces reactive capillary hemangiomas (RCHs). Routine clinical management of this unique and prevalent toxicity has been summarized in previous studies. The objective of this study was to provide evidence of apatinib as a salvage therapy for RCHs. MATERIALS AND METHODS: In this single-center, observational study, patients with NSCLC who were over 18 years of age and treated with camrelizumab were enrolled. The incidence of RCHs, onset and duration time, severity, evolution, and clinical practices, especially with apatinib, for their management and impact on quality of life, were recorded during a 6-month follow-up. RESULTS: A total of 28 patients were included. The incidence of RCHs was 28.6% (8/28). The median onset and duration time were 6 weeks and 8 weeks, respectively. Six (21.4%) patients had mild and moderate RCHs and four (9.3%) patients achieved a rapid regression of RCHs with the application of apatinib. The impact of the RCHs on quality of life was limited and assessed with Dermatology Life Quality Index scores. No treatment-associated termination was observed. CONCLUSION: The combination of camrelizumab and apatinib in the treatment of NSCLC reduced the incidence of RCHs. Apatinib appeared to be a salvage therapy of RCHs, which leads to rapid regression of RCHs with no impairment on the quality of life.

Infantile hemangiomas: our current understanding and treatment options.

Infantile hemangioma (IH) is the most common vascular tumor of infancy, affecting up to 10% of all infants. Our understanding of IH and its management has greatly evolved. The etiology of IH is unclear but hypoxia is thought to play a key role. Furthermore, GLUT1, IGF2, and HIF-1-? are thought to be important mediators. Current management options include active observation, medical treatment, and surgical intervention. The goals of treatment are preventing cosmetic disfiguration, psychosocial distress, and life-threatening complications. Infantile hemangioma should be managed with an individual, patient-centered approach. Generally, uncomplicated IH can be observed up to 18 months. However, IH should be treated in the setting of bleeding, ulceration, functional compromise, or eventual failure to regress.

Difficulties in the management of retinal capillary haemangiomas associated with von Hippel Lindau disease. / Dificultades en el manejo de los hemangiomas capilares retinianos asociados a enfermedad de von Hippel-Lindau.

CLINICAL CASE: A 29-year-old female with bilateral retinal capillary haemangiomas (RCH). A genetic analysis was carried out due to the suspicion of von Hippel-Lindau (VHL) disease, with negative results on 2occasions. There was progression of the RCH in the left eye, leading to a macular epiretinal membrane. The patient was treated with laser, intravitreal ranibizumab, and vitrectomy. Finally, a third genetic test detected a de novo mutation in the VHL gene, and led to the genetic diagnosis. DISCUSSION: VHL syndrome causes a complex ocular disease with a difficult diagnosis that requires early treatment of the RCH in order to modify its visual prognosis.

Vascular Ehlers-Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci: A case report.

RATIONALE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. PATIENT CONCERNS: We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. DIAGNOSES: Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. INTERVENTIONS: The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. OUTCOMES: Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. LESSONS: To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical suspicion of a possible connective tissue disorder when we encounter cases with atypical presentation and/or unique chest radiologic findings especially in young patients.

Histochemical Evaluation of the Vessel Wall Destruction and Selectivity After Treatment with Intense Pulsed Light in Capillary Malformations.

BACKGROUND: Among the different approaches for improving the effectiveness in the treatment of Capillary Malformations type Port Wine Stain (CM type PWS) are the intense pulsed light sources. There are few clinical studies prove useful in the treatment of CM. Furthermore, no studies have been published yet demonstrating the histological effects of IPL in CM. OBJECTIVES: To assess the histological effects of pulsed light in capillary malformations type port wine stain. We wanted to compare epidermal, dermal and vessel wall damage after treatment with different combinations of IPL parameters. MATERIAL AND METHODS: Fifty-five post-treatment biopsies were performed in 15 consenting patients with CM and stained with nitroblue-tetrazolium chloride (NBTC). Patients had not been treated previously. RESULTS: Fifteen patients with CM, with a median age of 39 years-old were enrolled in this study. In this series, the patients with the most severe epidermal damage were those with a darker phototype. Pink CM were especially resistant to treatment, even using high fluences, short pulse durations and stacking pulses. Longer intra- and interpulse delays were effective in purple CM, achieving adequate vessel destruction. CONCLUSIONS: IPL devices provide a vast amount of treatment possibilities and further studies are necessary to optimize therapeutic approaches to CM. In this study we have observed the histological effects of different pulses on the MC type PWS.

SPONTANEOUS RESOLUTION OF MACULAR EPIRETINAL MEMBRANES AFTER FLUORESCEIN POTENTIATED ARGON LASER TREATMENT OF VON HIPPEL-LINDAU ASSOCIATED RETINAL HEMANGIOMAS: CASE REPORT AND REVIEW OF LITERATURE.

PURPOSE: To illustrate spontaneous resolution of macular epiretinal membranes and inactivation of retinal hemangioma exudation after fluorescein potentiated argon laser treatment of bilateral capillary hemangiomas in a patient with a de novo heterozygous deletion in Exon 2 of the von Hippel-Lindau gene. METHODS: Interventional case report. RESULTS: A 23-year-old man with subjective complaints of blurry vision, photophobia, and glare. On presentation, visual acuity was 20/20 in the right eye and 20/25 in the left eye with metamorphopsia. On the basis of bilateral retinal hemangiomas on clinical examination and characterization with multimodal imaging, a diagnosis of von Hippel-Lindau disease was made. Genetic testing identified a de novo, disease-causing heterozygous deletion in Exon 2 of the von Hippel-Lindau gene. The patient underwent 4 sessions of fluorescein potentiated 532 nm argon green laser treatment directed at retinal hemangiomas. No adverse sequelae of laser treatment were noted. Seven months after the initial presentation, the patient's vision was 20/20 in both eyes with interval resolution of metamorphopsia. There was spontaneous resolution of a macular epiretinal membrane with normalization of the macular retinal microstructure. The retinal hemangiomas in both eyes appeared inactive, and no new lesions were noted. CONCLUSION: Fluorescein potentiated argon laser successfully treated bilateral retinal hemangiomas in our patient with von Hippel-Lindau disease. Additional studies to characterize the full clinical potential of fluorescein potentiated argon laser therapy may be warranted.

[Infantile segmental hemangioma without facial involvement: A cutaneous marker of vascular malformations such as in PHACE syndrome?]. / Hémangiome infantile segmentaire extra-facial : un marqueur cutané de malformations vasculaires comme au cours du syndrome PHACE ?

BACKGROUND: Herein we report a case of a possible PHACE syndrome without hemangioma of the head but with a large segmental hemangioma of the trunk. PATIENTS AND METHODS: A 17-year-old female patient with a medical history of transposition of the great arteries with ventricular septal defect diagnosed at 3 days of life and of coarctation of the aorta diagnosed at 14 years was seen in the dermatology department for a long-standing large rectangular, segmental, atrophic and telangiectasic lesion on her back. The lesion appeared to be a sequel of infantile segmental hemangioma of the trunk, and this was confirmed by history-taking. DISCUSSION: This case raises the question of a link between infantile segmental hemangioma and underlying cardiovascular disorders. Infantile segmental hemangioma could be a marker of an underlying vascular development defect. The presence of infantile segmental hemangioma, regardless of site, should prompt vascular explorations.

Educational paper: Pathogenesis of infantile haemangioma, an update 2014 (part I).

UNLABELLED: Infantile haemangioma (IH) is the most frequent childhood tumour. Although it is benign and self-limiting, severe complications can arise due to localisation and fast tumour growth. Management and therapy of IH has changed greatly after 2008 with propranolol. However, the pathogenesis remains elusive. This update provides an overview of all possible mechanisms currently considered. We discuss the possibility that several mechanisms act together, although local hypoxia seems to be important. Clinically, in about half of the cases, an IH is preceded by an anaemic macula (local ischaemia) or a so-called precursor lesion. Laboratory findings indicate stabilisation and an increased transcription activity of hypoxia-inducible factor 1 alpha (HIF1α), leading to up-regulation of its downstream target genes (such as vascular endothelial growth factor (VEGF)), which normally occurs in cases of hypoxia. CONCLUSION: Three main hypotheses have been proposed, namely (1) the theory of tissue hypoxia, (2) the theory of embolization of placental endothelial cells and (3) the theory of increased angiogenic and vasculogenic activity.

Co-development of pyogenic granuloma and capillary hemangioma on the alveolar ridge associated with a dental implant: a case report.

INTRODUCTION: The development of various benign oral mucosal lesions associated with dental implants, such as pyogenic granuloma or peripheral giant cell granuloma, has been rarely reported. However, the occurrence of vascular diseases, such as hemangioma, related to dental implants has not been explored in the literature. In this study, we report a case of co-development of pyogenic granuloma and capillary hemangioma on the alveolar ridge associated with a dental implant in a patient undergoing antithrombotic therapy. To the best of our knowledge, this is first case of hemangioma formation associated with a dental implant. CASE PRESENTATION: A 68-year-old Korean man was referred for intermittent bleeding and a dome-shaped overgrowing mass on his upper alveolar ridge. He underwent dental implantation 5 years ago, and was started on warfarin for cerebral infarction a year ago. He had experienced gum bleeding and gingival mass formation 6 months after warfarinization; then, his implant fixture was removed. However, his gingival mass has been gradually increasing. The gingival mass was surgically excised, and revealed the coexistence of pyogenic granuloma and capillary hemangioma in histological analysis of the specimen. The lesion has showed no recurrence for more than a year. CONCLUSIONS: Regarding immunostaining features, the endothelial cell markers, CD34 and CD31, and the mesenchymal cell marker, vimentin, were strongly detected, but cell proliferation marker, Ki-67, was negatively expressed in the endothelial cells of the hemangioma portion. However, in the pyogenic granuloma portion, CD34 was almost negatively detected, whereas vimentin and Ki-67 were highly detected in the fibroblast-like tumor cells. According to these heterogeneous characteristics of the lesion, the patient was diagnosed with coexistence of pyogenic granuloma and capillary hemangioma associated with the dental implant on the attached gingiva. We recommend that patients with dental implants who have chronic peri-implantitis under antithrombotic therapy should be closely followed to ensure early detection of oral mucosal abnormalities.

[Two cases of treatment for juxtapapillary hemangioma associated with von Hippel-Lindau disease].

BACKGROUND: We compared therapeutic outcomes in two cases of juxtapapillary capillary hemangiomas associated with von Hippel-Lindau disease. CASES: Case 1 was a 47-year-old man whose left eye was blind due to proliferative vitreoretinopathy. Visual acuity of the right eye was 1.2. No exudative change was found, but the juxtapapillary retinal hemangioma was enlarged. Three injections of intravitreal bevacizmab were not effective and laser photocoagulation was performed. Humphry microperimetry revealed a decreased sensitivity corresponding to the papillo-macular bundle damage. Vision was restored with regression of the retinal hemangioma. Case 2 was a 36-year-old woman with bilateral visual acuity of 1.2. The right eye had an inferior juxtapapillary retinal hemangioma at the optic disc surrounded by exudative retinal detachment. Laser photocoagulation, intravitreal injection of bevacizmab, transpapillary thermotherapy, photodynamic therapy, and vitrectomy were performed, but vision decreased to 0.02. CONCLUSIONS: Photocoagulation in the early stage of juxtapapillary hemangioma before development of exudative detachment may preserve visual acuity.

[De novo growth of a capillary hemangioma of the conjunctiva]. / Crecimiento de novo de un hemangioma capilar conjuntival.

CLINICAL CASE: A 22-year-old woman patient, diagnosed with an inclusion cyst of the conjunctiva in the nasal sector of the left eye, who after 2 shot/needle injections in the lesion came to our clinic with a dense subconjunctival hemorrhage in four quadrants and with severe pain. After excision biopsy, a capillary hemangioma of the conjunctiva was diagnosed. DISCUSSION: Conjunctival capillary hemangioma is mainly a benign lesion, asymptomatic and mostly congenital in origin, its progression or de novo growth is rare in adulthood.

Capillary haemangioma in a 13-year-old boy.

This case presents a 13-year-old boy who developed an unusual skin lesion on his chest that occurred after 2-3 weeks following a traumatic injury. The lesion was raised and bled easily. It was surgically removed via shave excision and treated with electrocautery. The patient healed with no recurrence and minimal scarring. Pathology determined the skin lesion to be a capillary haemangioma.