Small, vascular, red and violet lesions - Clinical Advisor

Small, vascular, red and violet lesions

Slideshow

  • Case #1

    August 2015 Dermatology Look-Alikes

    Case #1

  • Case #2

    August 2015 Dermatology Look-Alikes

    Case #2

Case #1

A woman, aged 45 years, presents for a routine skin check and complains of bright red spots on her chest and abdomen. She reports that these spots have increased in number over the years. The patient developed the first lesion when she was aged approximately 30 years. She states some lesions have also increased in size and are bothersome to her. She recalls her mother and sister having the same lesions. She has not tried any therapy but admits to sometimes accidentally scratching them.

Case #2

A 72-year-old white male presents with blue-red papules on his scrotum that have been present for the last six years. The lesions are only on the scrotum. He reports no pain, bleeding, or pruritus associated with the lesions. He is sexually active in a monogamous relationship. The patient has developed a few new similar lesions over the past year. He has never had a biopsy and has never tried any treatments. He would like to make sure the lesions are not “cancer.”


This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Reddish ulceration on a neonate’s face and Large patch of coalescing gray-brown macules. Then take the post-test here.


Case #1Cherry angiomas, which are also known as cherry hemangiomas, Campbell de Morgan spots, and senile angiomas, are a benign, cutaneous vascular proliferation that manifests as smooth, dome-shaped, circular or oval papules or macules that range in size from a...

Submit your diagnosis to see full explanation.

Case #1

Cherry angiomas, which are also known as cherry hemangiomas, Campbell de Morgan spots, and senile angiomas, are a benign, cutaneous vascular proliferation that manifests as smooth, dome-shaped, circular or oval papules or macules that range in size from a pinpoint to one-quarter of an inch in diameter. Most often, cherry angiomas arise on the trunk and upper extremities as one or more spots, but they are occasionally found at other anatomic locations. They typically range in color from cherry red to purple, but deep blue to black pigmentation may occur. 


Cherry angiomas are a common cutaneous vascular proliferation. They affect individuals of all races and ethnic backgrounds uniformly, but they are most apparent on pale-skinned individuals. The incidence of cherry angiomas increases with age. Usually, the lesions spontaneously develop in middle-aged and older individuals, and after presentation, the lesions may grow and increase in number. It is estimated that approximately 78% of adults aged more than 70 years have cherry angiomas.1 Angiomas that cluster together form a polypoid angioma.


The etiology of cherry angiomas is not well-understood. It has been suggested that the aging process is involved in the pathogenesis of cherry angiomas since they tend to present at middle or older age. In addition to age, cherry angiomas have been linked to exposure to chemicals including bromides and mustard gas.2,3 Sudden onset of cherry angioma may be a sign of an underlying hematologic disease.4 Certain hormonal factors may also contribute to the development of cherry angiomas, as lesional outbreaks have been linked to pregnancy and an increase in prolactin.5,6

One investigation has proposed that down-regulation of a specific micro-ribonucleic acid (miRNA) in cherry angiomas may contribute to abnormal angiogenesis via mitogen-activated protein kinase 1 (MEK1) and cyclin E1.7 The study revealed that in cherry angiomas, levels of miRNA 424 (mir-424) are lower relative to normal skin and other vascular anomalies, and protein expression of MEK1 and cyclin E1, the predicted targets of mir-424, was increased in the lesions. Furthermore, when endothelial cells were transfected with a mir-424 inhibitor, protein expression of MEK1 and cyclin E1 increased, and cell proliferation was induced. Thus, the mir-424-MEK1-cyclinE1 pathway may regulate cell proliferation in cherry angiomas.7 It is possible that new treatments for cherry angiomas may be developed using miRNA. 


Histopathologic examination of cherry angiomas reveals features consistent with true capillary hemangiomas. Histologically, cherry angiomas contain a proliferation of markedly dilated, often congested blood vessels with variably thickened walls, which decrease in caliber with increasing depth.8,9 The overlying epidermis may appear normal or slightly thinned.9 Well-developed lesions may be polyploid and have an epidermal collarette.9 Cherry angiomas are further distinguished from normal skin by their distinctly higher density of mast cells.10

The clinical differential diagnosis of cherry angioma includes nodular melanoma, angiokeratoma, pyogenic granuloma, insect bites, blue rubber bleb nevus syndrome, and petechiae. Diagnosis of cherry angioma is typically accomplished by visual inspection. Cherry angiomas can normally be distinguished from other pigmented lesions by their characteristic cherry-red color and smooth, dome-shaped surface, their tendency to appear during the third or fourth decade of life on the trunk and/or upper extremities, and their asymptomatic nature. If the lesion is dark-red, blue, or black in color, the lesion may be a cherry angioma that contains partially or completely thrombosed blood vessels. 


In clinically suspicious lesions, dermoscopy can be a useful tool. Dermoscopic criteria that favor diagnosis of cherry angiomas are multiple, well-demarcated, round-to-oval lacunae that range in color from red to blue-black, and the absence of pigmented networks, globules, or branched streaks.11 If there is clinical uncertainty, the diagnosis of cherry angioma can be confirmed with a biopsy. 


Cherry angiomas are clinically asymptomatic and typically require no treatment, but they are subject to profuse bleeding upon physical trauma. The main concern with cherry angiomas is that their appearance can be distressing for patients, especially when the lesions are located on a noticeable site. Cherry angiomas are traditionally removed by shave excision, cryosurgery, and electrocauterization. More recently, laser therapies, including pulsed dye laser (PDL), intense pulsed light (IPL), and neodymium: yttrium-aluminum-garnet (Nd:YAG) laser have become popular treatment methods. Most cherry angiomas will not disappear without treatment.


PDL is the preferred laser therapy for cherry angiomas.12 PDLs emit a 585-nm wavelength to the angioma with a relatively short pulse duration of 450 microseconds, which limits the laser’s penetration depth to 1.5 mm. IPL devices deliver a non-coherent light beam with a wavelength from 500 nm to 1200 nm at variable pulse durations, which allows them to target vessels at deeper points and cavernous vascular lesions.12,13 Most Nd:YAG lasers deliver a wavelength of 1064 nm.12

The majority of cherry angiomas respond to a single laser treatment, but larger angiomas may need multiple treatments. Complications are uncommon for laser therapy, but red or bruised discoloration of the treated area and slight swelling may occur. In rare cases, textural changes, blistering, or scarring may appear.14

Because laser parameters vary with area, type of lesion, skin color, and depth of lesion, the clinician should assess the patient’s specific needs to determine which treatment is appropriate.12 Sun exposure should be limited before and after treatment; patients with excessive sun exposure before laser treatment may not respond as well to therapy, and patients with excessive sun exposure after laser therapy are more likely to display hyperpigmentation of the treated region.14

The patient in this case was reassured of the diagnosis. She was offered elective electrodesiccation for cosmetic treatment of the lesions, but she declined.


Case #2

Angiokeratoma, a vascular anomaly that manifests as small, pinpoint to pea-sized papules.15 The papules range from 2 mm to 10 mm and are initially soft and red, but with time, they can become firm, turn blue-black in color, develop a rough and scaly surface, and resemble a melanocytic lesion or wart.16 Angiokeratomas can occur on all parts of the body, but the most common sites of appearance are the lower extremities. 


There are five types of angiokeratoma, which differ by their age of onset, cause, location, and clinical manifestation: (1) Mibelli type; (2) Fordyce type; (3) angiokeratoma corporis diffusum; (4) angiokeratoma circumscriptum naeviforme; and (5) solitary or multiple papular angiokeratoma.16

Angiokeratoma of the Mibelli type manifests during childhood to adolescence as hyperkeratotic vascular lesions over the bony prominences of the extremities, especially on the dorsa of the fingers and toes.17 The Fordyce type is characterized by papules that normally present on the scrotum or vulva but may extend to the penis, upper thigh, and lower abdomen. Angiokeratoma of the Fordyce type typically manifests during the second to third decade of life.17 Angiokeratoma corporis diffusum, also known as Fabry disease, is an X-linked inherited disorder that is caused by a deficiency of the enzyme alpha-galactosidase A. Lack of this enzyme causes abnormal deposition of glycosphingolipids within lysosomes of different cell types, especially endothelial cells, ultimately leading to cardiovascular and renal complications.18 Symptoms of Fabry disease typically begin in adolescence and increase in severity with age.17 Papules commonly present during childhood on the hands, knees, elbows, and flanks, but they can spread to involve the genitals, lumbosacral area, gluteal cleft, trunk, lips, umbilicus, periungual areas, and palms.18 Angiokeratoma circumscriptum is characterized by unilateral nevoid vascular lesions arranged in streaks and bands, which present at birth and often are located on the lower extremities.17 Lastly, the solitary and multiple papular types of angiokeratoma are usually seen on the lower extremities of young adults.17

Histological examination reveals that angiokeratomas share similar histopathologic features: (1) marked dilation of superficial papillary vessels that form cavernous spaces; (2) overlying epidermal acanthosis, variably prominent hyperkeratosis, and elongation of the rete ridges that may surround vascular channels; (3) intimate vascular and epidermal association; and (4) a lack of dilated vessels in the underlying dermis or lobules of capillaries.16,17

To distinguish between the different types of angiokeratomas, the clinician should assess the clinical features and location of the lesions as well as personal and family history. Skin biopsy, dermoscopy, and electron microscopy can aid diagnosis.18,19

Isolated angiokeratomas are common benign cutaneous lesions, but diffuse angiokeratomas should alert the clinician of a possible diagnosis of Fabry disease. Early manifestations of Fabry disease include gastrointestinal disturbances, episodes of pain in the hands and feet, hypohidrosis, fever, and tinnitus.18 If the clinical features suggest Fabry disease, the diagnosis can be confirmed by an enzyme assay to measure alpha-galactosidase activity in males and by molecular genetic analysis of the GLA (galactosidase, alpha) gene in females.18 Due to the progressive nature of Fabry disease, early diagnosis and treatment of the disease is important to prevent irreversible organ damage.19

Aside from Fabry disease, which is caused by a genetic mutation, the cause of angiokeratomas is not understood. 


Diseases that mimic angiokeratoma include melanoma, cherry angiomas, pyogenic granuloma, seborrheic keratosis, and genital warts. Dermoscopy can be a useful diagnostic tool, as the dermoscopic pattern of angiokeratomas is characterized by well-defined red or dark lacunae with a whitish veil.19 Biopsy is indicated if the diagnosis is in doubt. 


Solitary angiokeratomas may resemble nodular melanoma, but diagnosis of malignant melanoma is favored if the lesion has undergone rapid growth or bled. Unlike melanocytic lesions, angiokeratomas do not show pigmented networks, globules, or branched streaks on dermoscopy.11

Angiokeratomas and cherry angiomas both manifest as small, vascular, and benign spots. Both can be red-violet in color and can occur as multiple lesions anywhere on the body, but angiokeratomas are usually found on the scrotum or extremities. Age of presentation is important to distinguish between cherry angiomas and angiokeratomas. Cherry angiomas are frequent in the elderly, whereas angiokeratomas commonly present in adolescents and young adults. Unlike the hyperkeratotic lesions of angiokeratoma, the overlying epidermis of cherry angiomas is not hyperkeratotic and rarely rough or warty in appearance. Lacunae in angiokeratomas tend to be morphologically less well-defined than in cherry angiomas.11

Solitary angiokeratoma can be differentiated from pyogenic granuloma by the presence in pyogenic granuloma lesions of inflammatory cells, an ulcerated surface, and lobules of capillary-like vessels embedded in myxoid and fibroblastic stroma.17

Dermoscopic features that favor a diagnosis of seborrheic keratosis rather than angiokeratoma include milia-like cysts, comedo-like openings, fissures and ridges, fingerprint-like structures, a moth-eaten border, hairpin blood vessels, and network-like structures.11

Genital warts tend to be more firm in texture and more irregular in distribution than angiokeratoma. In addition, angiokeratoma is non-infectious, unlike genital warts, which are spread by sexual contact. 


Angiokeratomas are typically clinically asymptomatic, but they occasionally bleed or cause pain and itching. For cosmesis, there are several options for treatment. For the Mibelli type of angiokeratoma, treatment options include liquid nitrogen, electrodessication, laser ablation, or local excision.20 The Fordyce type of angiokeratoma can be removed with liquid nitrogen cryotherapy, diathermy, or laser ablation.20 Small lesions of angiokeratoma circumscriptum can be treated with curettage and cautery; large lesions can be excised or removed by laser therapy.20 Solitary papular angiokeratomas can be locally excised.20 To treat the dermatologic features of Fabry disease, laser therapy and liquid nitrogen treatments should be considered.21

The patient in this case was reassured of the diagnosis, and he declined elective destruction of the lesions. Follow-up was not needed.

Kate Travis, BA, is a medical student and Rana Mays, MD, is a dermatology resident at Baylor College of Medicine in Houston. 


References


  1. Plunkett A, Merlin K, Gill D, et al. The frequency of common nonmalignant skin conditions in adults in central Victoria, Australia. Int J Dermatol. 1999;38(12):901-908. 

  2. Aghaei S, Moradi A. Eruptive cherry angiomas secondary to exposure to sulfur mustard gas. The Internet Journal of Dermatology. 2010;8(2). Available at ispub.com/IJD/8/2/9937 

  3. Cohen AD, Cagnano E, Vardy DA. Cherry angiomas associated with exposure to bromides. Dermatology. 2001;202(1);52-53.

  4. Fajgenbaum DC, Rosenbach M, van Rhee F, et al. Eruptive cherry hemangiomatosis associated with multicentric Castleman disease: A case report and diagnostic clue. JAMA Dermatol. 2013;149(2):204-208. Available at archderm.jamanetwork.com/article.aspx?articleid=1654890 

  5. Askari N, Vaez-Mahdavi MR, Moaiedmohseni S, et al. Association of chemokines and prolactin with cherry angioma in a sulfur mustard exposed population—Sardasht-Iran cohort study. Int Immunopharmacol. 2013;17(3):991-995. 

  6. Requena L, Sangueza OP. Cutaneous vascular proliferation. Part II. Hyperplasias and benign neoplasms. J Am Acad Dermatol. 1997;37(6):887-922. 

  7. Nakashima T, Jinnin M, Etoh T, et al. Down-regulation of mir-424 
contributes to the abnormal angiogenesis via MEK1 and cyclin E1 in senile hemangioma: Its implications to therapy. PLoS One. 2010;5(12):e14334. Available at journals.plos.org/plosone/article?id=10.1371/journal.pone.0014334 

  8. Aghassi D, Anderson RR, González S. Time-sequence histologic imaging of laser-treated cherry angiomas with in vivo confocal microscopy. J Am Acad Dermatol. 2000;43(1 Pt 1):37-41. 

  9. Hornick JL. Practical Soft Tissue Pathology: A Diagnostic Approach. 1st ed. Philadelphia, Pa.: Saunders-Elsevier; 2013:341-342. 

  10. Hagiwara K, Khaskhely NM, Uezato H, Nonaka S. Mast cell “densities” in vascular proliferations: A preliminary study of pyogenic granuloma, portwine stain, cavernous hemangioma, cherry angioma, Kaposi’s sarcoma, and malignant hemangioendothelioma. J Dermatol. 1999;26(9):577-586. 

  11. Malvehy J, Braun RP, Puig S, et al. Handbook of Dermoscopy. London: Taylor & Francis Group; 2006:7-17.
  12. Srinivas CR, Kumaresan M. Lasers for vascular lesions: Standard guidelines of care. Indian J Dermatol Venereol Leprol. 2011;77(3):349-368. Available at ijdvl.com/text.asp?2011/77/3/349/79728 

  13. Goldberg DJ. Current trends in intense pulsed light. J Clin Aesthet Dermatol. 2012;5(6):45-53. Available at ncbi.nlm.nih.gov/pmc/articles/PMC3390232 

  14. Wall TL. Current concepts: Laser treatment of adult vascular lesions. Semin Plast Surg. 2007;21(3):147-158. Available at ncbi.nlm.nih.gov/pmc/articles/PMC2884838 

  15. Trindade F, Torrelo A, Kutzner H, et al. An immunohistochemical study of angiokeratomas of children. Am J Dermatopathol. 2014;36(10):796-799. 

  16. Hornick JL. Practical Soft Tissue Pathology: A Diagnostic Approach. 1st ed. Philadelphia, Pa.: Saunders-Elsevier; 2013:330-331. 

  17. Imperial R, Helwig EB. Angiokeratoma: A clinicopathological study. Arch Dermatol. 1967;95(2):166-175. 

  18. Zampetti A, Orteu CH, Antuzzi D, et al. Angiokeratoma: Decision-making aid for the diagnosis of Fabry disease. Br J Dermatol. 2012;166(4):712-720. 

  19. Kim JH, Kim MR, Lee SH. Dermoscopy: A useful tool for the diagnosis of angiokeratoma. Ann Dermatol. 2012;24(4):468-471. Available at ncbi.nlm.nih.gov/pmc/articles/PMC3505781 

  20. Sacchidanand S, Savitha AS, Shilpa K, eds. Snapshots in Dermatology. 1st ed. New Delhi: Jaypee Brothers Medical Publishers Ltd; 2013:40-43. 

  21. Eng CM, Germain DP, Banikazemi M. Fabry disease: Guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006;8(9):539-548. Available at nature.com/gim/journal/v8/n9/full/gim200691a.html 


All electronic documents accessed on August 4 2015.


Next hm-slideshow in Clinical Quiz