Angiokeratoma of tongue in the pediatric age group: a rare presentation.

BACKGROUND: Angiokeratoma is a rare cutaneous presentation with unknown etiology. CASE PRESENTATION: A case of a 10-year male, who was presented to the ENT OPD with a swelling over the posterior aspect of the tongue. The chief complaints included growth on the right side of the posterior third of the tongue which was extending up to the base of the tongue on the same side. CONCLUSION: Excisional biopsy was taken and sent for histopathology which was suggestive of inflamed angiokeratoma. Post-excision there is no recurrence till date.

[Multisystem lesions in orphan diseases: rheumatological aspects of Fabry's disease. Case report].

Fabry-Andersen disease is a genetically determined, progressive disease related to lysosomal storage diseases, linked to the X chromosome, characterized by impaired glycosphingolipid metabolism, due to the deficiency or absence of the enzyme α-galactosidase A. Fabry disease is a multisystem disease and is characterized by damage to vital organs - kidneys, heart, brain, with the occurrence of complications that cause an unfavorable prognosis. Autoinflammation mechanisms with signs of chronic inflammation are involved in the pathogenesis of the disease. One of the features of Fabry disease are clinical manifestations in the form of arthralgia, fever, skin lesions, which are similar to rheumatological diseases. The article presents a clinical observation of the classical type of Fabry disease with multiple organ manifestation, which required differential diagnosis with rheumatological diseases. Rheumatologists are specialists who are involved in the early diagnosis of Fabry disease, so they should have a high awareness of this sphingolipidosis.

Angiokeratoma corporis diffusum with severe acroparesthesia, an endothelial abnormality, and inconspicuous genetic findings.

Angiokeratoma corporis diffusum (ACD) was long thought to be a specific dermal sign of Fabry disease (FD, X-linked alpha-galactosidase A [GLA] deficiency). However, other lysosomal storage diseases (LSDs) have also been identified as triggers of ACD. Generalized vasculopathy is an important pathogenetic factor in FD and may also lead to the acroparesthesia (AP) often predominant in FD. We report on an 85-year-old woman with ACD present since her youth and associated with severe AP. Ultrastructure of the dermal lesion showed no lysosomal involvement, but the absence of the basement membrane of the endothelial cells of the capillary vessels was noteworthy. Repeated analyses of the GLA gene revealed no evidence of FD. Whole-exome sequencing was negative for FD and other LSDs, and allowed us to also study FD-related intronic regions of the GLA gene. This is the first report of a patient with FD-like ACD with an endothelial abnormality, otherwise unexplained vasculopathy and severe AP, which are not due to FD or another LSD. Based on family history, another genetic, yet unidentified, defect may cause the disease in this patient. In unexplained ACD, extended genetic analysis is required to exclude particular pathogenic variants of the GLA gene and other genes.

Verrucous venous malformation with thrombocytopenia in a neonate.

Verrucous venous malformations (VVM) are rare, congenital, slow-flow vascular anomalies that have been historically difficult to characterize due to clinical mimics and unclear histological evaluation. A life-threatening complication of VVMs is localized intravascular coagulation. Herein, we describe a male neonate who presented with a congenital VVM on the left lower extremity with associated severe thrombocytopenia. We discuss the multifaceted diagnostic approach used to identify this VVM, while highlighting the use of WT-1 as a negative predictive marker; we additionally outline novel treatment options and management beyond cutaneous involvement.

Eccrine angiokeratomatous hamartoma combined with solitary angiokeratoma or verrucous venous malformation: Report of two cases and comprehensive review of the literature.

First reported in 2006, eccrine angiokeratomatous hamartoma is a very rare vascular malformation of the skin, with only few described cases. It has a peculiar histopathology with features deriving from the combination of two different vascular malformations of the skin: solitary angiokeratoma and eccrine angiomatous hamartoma. In the past, other authors described similar hamartomatous lesions with features deriving from verrucous venous malformation and eccrine angiomatous hamartoma. We believe that these lesions are clearly overlapping from clinical, histopathological, and immunohistochemical points of view and the term "eccrine angiokeratomatous hamartoma" should be used to indicate the whole spectrum of these lesions as suggested by Kanitakis et al. Herein we present two cases of this rare vascular hamartoma, with clinical, histopathological and immunohistochemical characterization. In addition, for the first time we report a complete and detailed review of the literature to clarify the clinical, epidemiological, and histopathological features of this unique entity.

Topical sirolimus for treatment of a solitary angiokeratoma.

Angiokeratomas are benign vascular neoplasms that arise as solitary or multiple lesions, most commonly treated with excision, electrodessication, cryotherapy, or laser therapies. This case presents a young female whose solitary angiokeratoma was treated with topical 1% sirolimus cream, improving the appearance, symptoms, and size of the lesion. Topical sirolimus cream may be a noninvasive treatment option for angiokeratomas with fewer risks than standard therapy that may be feasible and preferable for some patients.

Enoxaparin induced eruptive angiokeratoma, an extremely rare side effect.

Enoxaparin is one of the most commonly used anticoagulants in the management of thromboembolic events. Herein we report a unique case of enoxaparin induced eruptive angiokeratomas in a patient with a history of ischemic cardiomyopathy who presented with acute decompensated heart failure and a new-onset generalized skin rash that bleeds on trauma, suggestive of angiokeratomas. Dermoscopic examination, as well as skin biopsy, were done upon clinical suspicion of eruptive angiokeratomas, to confirm the diagnosis. Dermoscopy showed dark lacunae surrounded by erythema, while skin biopsy revealed dilated congested capillaries lined by flat endothelial cells in the papillary dermis, both confirming the diagnosis of angiokeratoma. Enoxaparin induced eruptive angiokeratomas was suspected when the skin eruption showed spontaneous dramatic resolution upon withdrawal of enoxaparin followed by its substitution with warfarin, during the course of the patient's treatment. Enoxaparin induced eruptive angiokeratoma is an extremely rare side effect. Physicians should have a high index of clinical suspicion, and promptly discontinue the drug, as this is the only proven treatment for this condition.

Use of topical rapamycin in acral pseudolymphomatous angiokeratoma of children (APACHE): A report of two cases and review of the literature.

Acral pseudolymphomatous angiokeratoma of children (APACHE) is a rare, benign disease characterized clinically by multiple, asymptomatic, erythematous papules in the acral regions. We report APACHE in a 12-year-old girl with erythematous-violaceous papules on the lateral dorsum of her foot and toes, and a 3-year-old girl with erythematous papules on the plantar aspect of her foot. Topical rapamycin ointment improved the lesions and both patients tolerated the medication well. Topical rapamycin appears to be a potentially efficacious, well-tolerated, non-invasive therapy in APACHE, although further studies are needed.

[Diffuse hyperkeratotic papules of the lower abdomen and genital region in a 38-year old male patient]. / Diffuse hyperkeratotische Papeln am unteren Abdomen und im Genitalbereich bei einem 38­jährigen Patienten.

A patient with diffuse angiokeratomas of the lower abdomen and genital region was diagnosed with Fabry disease on the basis of genetic testing. Fabry disease is an X-linked lysosomal storage disease that can affect several organ systems including the heart or kidneys, resulting in reduced median survival. Pathogenetically, Fabry disease leads to a deficiency of the lysosomal enzyme α­galactosidase A (α-GAL A). Treatment options include lifelong enzyme replacement therapy or chaperone therapy.

A novel association between angiokeratoma corporis diffusum and acid sphingomyelinase deficiency.

Angiokeratoma corporis diffusum refers to symmetrical clusters of minute red papules in a "bathing trunk" distribution and is considered the cutaneous hallmark of Fabry disease. Acid sphingomyelinase deficiency is an autosomal recessive sphingolipidosis, which presents with massive hepatosplenomegaly, pulmonary infiltrates, and skeletal abnormalities. We present the unusual case of a 12-year-old girl with acid sphingomyelinase deficiency who developed characteristic lesions of angiokeratoma corporis diffusum.

Solitary plaque on the leg of a child: A report of two cases and a brief review of acral pseudolymphomatous angiokeratoma of children and unilesional mycosis fungoides.

Acral pseudolymphomatous angiokeratoma of children (APACHE) and unilesional mycosis fungoides (MF) are two rare dermatoses in the pediatric population which may have overlapping clinical and histopathologic features, making differentiation between these two diagnoses difficult. We present two similar cases of a solitary plaque on the thigh of a child, one representing APACHE and the other representing unilesional MF with granulomatous features, and we provide a brief overview of the clinical and histopathologic features of APACHE and unilesional MF.

Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions.

Fucosidosis is a rare lysosomal storage disease which has been classified into two subtypes, depending on the severity of clinical signs and symptoms. Fucosidosis patients' skin abnormalities include angiokeratoma corporis diffusum, widespread telangiectasia, thick skin, hyperhidrosis and hypohidrosis, acrocyanosis and distal transverse nail bands. It has been described that >50% of fucosidosis patients have angiokeratoma. At molecular level, fucosidosis is caused by lysosomal alpha-L-fucosidase (FUCA1) gene mutations. Obtaining samples for functional studies has been challenging due to the inherent difficulty in finding affected individuals. The effect of FUCA1 dysfunction on gene expression is unknown. The aim of this study was to analyse, in keratinocytes, the transcriptomic effect of FUCA1 knock-down for a better understanding of skin lesions' pathogenesis affecting fucosidosis patients. FUCA1 knock-down (siRNA) was performed in human HaCaT immortalised keratinocytes. Affymetrix arrays and qPCR were used for analysing gene expression. Bioinformatics was used for functional clustering of modified genes. In total, 387 genes showed differential expression between FUCA1 silenced and non-silenced cells (222 up-regulated and 165 down-regulated). Up-regulated genes belonged to two major groups: keratinocyte differentiation/epidermal development (n = 17) and immune response (n = 61). Several transcription factors were up-regulated in FUCA1-siRNA transfected cells. This effect might partly have been produced by abnormal transcription factor expression, that is FOXN1. We thus propose that fucosidosis-related skin lesions (eg angiokeratoma) and those of other diseases (eg psoriasis) might be caused by dysfunctions in common aetiological overlapping molecular cascades.

Utility and tolerability of the long-pulsed 1064-nm neodymium:yttrium-aluminum-garnet (LP Nd:YAG) laser for treatment of symptomatic or disfiguring vascular malformations in children and adolescents.

BACKGROUND: Vascular malformations manifest with pain, bleeding, disability, and disfigurement in a subset of children. There are scant data available on the utility and tolerability of laser surgery for symptomatic or disfiguring non-port-wine stain vascular malformations in children. OBJECTIVE: The objective of this study was to determine the utility and tolerability of the 1064-nm long-pulsed neodymium:yttrium-aluminum-garnet (LP Nd:YAG) laser for treatment of symptomatic or disfiguring vascular malformations in children. METHODS: We conducted a retrospective review of 29 pediatric patients with non-port-wine stain vascular malformations who were treated with the LP Nd:YAG laser at our institution. We report patient characteristics, treatment parameters, outcomes, and complications. RESULTS: Blinded assessment of clinical efficacy revealed good to excellent results in 66.7% of patients treated and poor to fair results in 25%. The overall rate of complications was 27%, with minor skin breakdown and blistering being the most common. LIMITATIONS: Our conclusions are limited by small sample size, pretreatment and posttreatment photographs in only a subset of patients, and lack of long-term follow-up. CONCLUSION: The LP Nd:YAG laser is a well-tolerated and effective treatment modality for a variety of non-port-wine stain vascular malformations in children.

Laser treatment of cutaneous angiokeratomas: A systematic review.

Angiokeratomas can present therapeutic challenges, especially in cases of extensive lesions, where traditional surgical methods carry high risks of scarring and hemorrhage. Argon, pulsed dye (PDL), neodymium-doped yttrium aluminum garnet (Nd:YAG), copper vapor, potassium titanyl phosphate, carbon dioxide, and erbium-doped yttrium aluminum garnet (Er:YAG) lasers have emerged as alternative options. To review the use and efficacy of lasers in treating angiokeratomas. A PubMed search identified randomized clinical trials, cohort studies, case series, and case reports involving laser treatment of cutaneous angiokeratomas. Twenty-five studies were included. Quality ratings were assigned using the Oxford Centre for Evidence-Based Medicine scheme. Several laser modalities are effective in treating multiple variants of angiokeratomas. Vascular lasers like PDL, Nd:YAG, and argon are the most studied and of these, PDL offers the safest side effect profile. Nd:YAG may be more effective for hyperkeratotic angiokeratomas. Combination treatment with multiple laser modalities has also demonstrated some success. Lasers are a promising treatment option for angiokeratomas, but current use is limited by the lack of treatment guidelines. There are limited high quality studies comparing laser treatments to each other and to non-laser options. Additional studies are needed to establish guidelines and to optimize laser parameters.

Genital angiokeratomas of Fordyce 595-nm variable-pulse pulsed dye laser treatment.

BACKGROUND: Angiokeratoma of Fordyce (AF) represents dark red or blue-black papules with a scaly surface located on scrotum, labia majora, and penis. Though usually asymptomatic, bleeding after mechanical trauma and sexual intercourse may occur. AF should be differentiated from malignant melanoma, angiosarcoma, and other pigmented lesions. The treatment, usually asked from patients as the result of anxiety and social embarrassment, should be performed in a non-aggressive manner. OBJECTIVES: To determine the safety and effectiveness of 595-nm variable-pulse pulsed dye laser (VPPDL) with a Dynamic Cooling Device (DCD) in the treatment of AF. METHODS: Twenty-four patients (22 men and two women) aged 40.88 ± 12.48 years with AF were included in the retrospective study. Lesions located on scrotum, labia majora, and penis were treated with 595-nm VPPDL in the intervals of one to three months. Variable spot, fluence, and pulse-width parameters were used with and/or without DCD skin cooling. RESULTS: AF were successfully removed in all patients in one to seven (mean ± SD = 3.38 ± 2.16) treatment sessions with no permanent side effects or complications such as dyspigmentations or scarring. Recidives were observed in four patients after 0.5-1 year intervals. CONCLUSIONS: 595-nm VPPDL with DCD represents an efficient and safe method for the removal of multiple lesions of AF in genital localization.

[Fabry disease]. / Maladie de Fabry.

Fabry disease, also known as Anderson-Fabry disease or angiokeratoma corporis diffusum universale, is an X-linked recessive form of sphingolipidosis caused by total or partial deficiency of the lysosomal hydrolase, alpha-galactosidase A. From the youngest age, it results in a gradual ubiquitous build-up of glycosphingolipids that are not degraded by the missing enzyme. Cutaneous, neurological, nephrologic, cardiac, gastrointestinal, ophthalmological, respiratory, cochleovestibular and haematological involvement are responsible for increased mortality and significant impairment of quality of life in subjects affected by the disease. Angiokeratomas are the most common cutaneous sign of this disease, although they are not specific to it and must be distinguished from angiokeratomas either occurring in isolation or associated with systemic diseases. Other cutaneous signs encountered in this disease include hyperhidrosis, oral lesions, lower limb oedemas, etc. The diagnosis is mainly clinical and should be considered in the presence of a personal and/or familial history; it is confirmed by assay of enzyme activity within leucocytes or by molecular studies. Management is multidisciplinary and involves symptomatic treatment as well as specific treatment, resulting in improved survival and enhanced quality of life for patients presenting the disease. Enzyme replacement therapy with alpha-galactosidase A forms the cornerstone of specific treatment and may be associated with other types of treatments such as galactose and molecular chaperones. Gene therapy is now also used extensively. At present, these marked therapeutic advances, which closely involve dermatologists, could help transform the prognosis for patients presenting Fabry disease.

Eruptive angiokeratomas and porokeratosis in the setting of sclerodermatous graft-vs.-host disease.

Porokeratosis and angiokeratomas are both seen in the setting of chronic graft-vs.-host disease (GVHD), but rarely occur together. We present a case of a patient with lichen planus-like (LPL) and sclerodermatous chronic GVHD manifesting after allogeneic bone marrow transplant with concomitant eruptive angiokeratomas and porokeratosis.

Angiokeratoma of Fordyce response to long pulsed Nd:YAG laser treatment.

Angiokeratoma of Fordyce can be easily diagnosed by their typical erythra and cured by varied therapeutic methods including surgery, electrocoagulation, cryotherapy, or various laser systems. Which are the optimal therapeutic methods? There are no consentaneous opinions in the reported articles. We present our characteristic treatment with the application of long pulsed neodymium-dopedyttrium-aluminum-garne (lpNd:YAG) laser in the treatment of angiokeratoma of Fordyce. A 1064 nm lpNd:YAG laser (spot size: 5 mm/7 mm, energy:90-130 J/cm(2) , and pulse duration: 10-20 ms.) was used to treat the patient's lesions. The desirable clinical endpoint of the treatment was lesions shrunk and turned pallor immediately after the irradiation. The treatment interval was at least 8 weeks. Of the 11 patients, 9 of them were cured and 2 of them were improved. The mean treatment sessions were 2.2 times. None of them had a scar formation and any other side effects. All of them were satisfied with the treatment results. We conclude that angiokeratoma of Fordyce responded well to lpNd:YAG laser treatment. It provided a simple, rapid, and no bleeding treatment in treating Angiokeratoma of Fordyce.