Dermatology

Angiokeratomas Mibelli and Fordyce

Angiokeratomas of Fordyce and Mibelli, ICD-9 709.1 (vascular disorders of skin)

Are You Confident of the Diagnosis?

Angiokeratoma is the term used to define benign acquired telangiectasias that are associated with overlying hyperkeratosis. Congenital lesions with similar clinical appearance and histology have been termed "hyperkeratotic vascular stains." Five clinical subtypes of angiokeratomas have been described: solitary angiokeratoma, angiokeratoma of Fordyce, angiokeratoma of Mibelli, angiokeratoma circumscriptum, and angiokeratoma corporis diffusum. Angiokeratomas are generally asymptomatic but can bleed with trauma and subsequently develop a hemorrhagic crust.

Characteristic findings on physical examination

A solitary angiokeratoma presents as a small, verrucous, blue to black papule, most commonly affecting the lower limbs.

Angiokeratoma of Fordyce consists of several, 1-6 mm, dark red to purple to blue-black vascular papules commonly arising on the vulva or scrotum, and occasionally on the penis (Figure 1).

Figure 1.

Multiple 1-4mm red to purple vascular papules on the scrotum.

Angiokeratoma of Mibelli is characterized by multiple dark blue-red or grey, hyperkeratotic to verrucoid, vascular papules. Classically, angiokeratoma of Mibelli occurs on the dorsa and web spaces of fingers and toes, but it has also been reported to occur on the knees, elbows and lateral quadrants of the breasts.

Angiokeratoma circumscriptum presents as unilateral, hyperkeratotic, grouped vascular papules. This may actually represent a vascular malformation of capillary or lymphatic origin, rather than true angiokeratoma.

The least common variant, angiokeratoma corporis diffusum, is composed of small, 1-mm, dark red papules located on the lower abdomen, buttocks, genatalia and thighs in a "bathing trunk" distribution presented in childhood through adulthood. Angiokeratoma corporis diffusum is often a cutaneous manifestation of hereditary enzymatic disorders of metabolism, including Fabry's disease (X-linked recessive alpha-galactosidase deficiency) and other lysosomal storage diseases.

The prognostic significance among the four subtypes varies greatly, from benign lesions without systemic implications to potentially fatal metabolic diseases. The remainder of this chapter will focus primarily on the following two subtypes: angiokeratoma of Fordyce and angiokeratoma of Mibelli.

Expected results of diagnostic studies

Histopathologic appearance is similar among the four subtypes of angiokeratomas. Within the superficial dermal papillae, there are ectatic, thin-walled blood vessels with lining of unremarkable endothelial cells with adjacent acanthosis, papillomatosis, and hyperkeratosis of the epidermis. Thrombosis may be identified within the vessels. The degree of hyperkeratosis is variable. It is often present in solitary angiokeratomas and is particularly marked in angiokeratoma of Mibelli, but may be absent in angiokeratoma of Fordyce and angiokeratoma corporis diffusum.

Diagnosis confirmation

When multiple thromboses develop in an angiokeratoma, it may clinically simulate a nodular melanoma. Dermoscopy is an important tool in differentiating between melanocytic (melanoma) and nonmelanocytic lesions (angiokeratoma).

Upon dermoscopic evaluation of an angiokeratoma, several large, sharply demarcated, round to oval areas of red, reddish-blue, blue-black or black discoloration along with yellow-white keratotic areas are observed. A reddish halo may be seen around the lesion, indicating recent trauma. Characteristics of a melanoma include asymmetric color distribution, irregular pigment network, peripheral aggregated globules and radial streamings, with or without a milky white veil.

Because of the hyperkeratosis, angiokeratomas may also grossly appear similar to verrucae.

Who is at Risk for Developing this Disease?

Angiokeratoma of Fordyce is a condition that most commonly affects elderly individuals, although similar lesions can occur in pregnant females or with the use of oral contraceptive pills.

Angiokeratoma of Mibelli is a condition that appears in childhood or adolescence (ages 10-15), and disproportionately affects females. An autosomal dominant familial form has been described.

What is the Cause of the Disease?

Etiology

Angiokeratomas are acquired vascular lesions that result from abnormal, permanent dilation of preexisting vessels in the dermis (including venules, capillaries, and arterioles) associated with an overlying hyperkeratotic epidermis. It is postulated that they may be due to a decrease in the supportive elastic tissues in the vessel walls.

Pathophysiology

Angiokeratoma of Fordyce have been reported to occur in association with inguinal hernias, varicoceles, thrombophlebitis, or trauma, and are speculated to occur secondary to localized venous hypertension, which also could explain the similar presentation seen in pregnant females. An association with radiotherapy has been reported for vulvar lesions. In addition, there are rare case reports of angiokeratoma of Fordyce developing after surgical treatment of genital neoplasms (cervical cancer s/p radical hysterectomy, penile cancer s/p penectomy and lymphadenectomy).

Cold temperatures are associated with the development of angiokeratoma of Mibelli. In fact, patients may have a history of acrocyanosis or chilblains (pernio), although this association has been debated.

Systemic Implications and Complications

Both angiokeratoma of Fordyce and Mibelli have no tendency toward spontaneous regression, and they are not premalignant. They tend to gradually increase in size and number.

Angiokeratoma of Mibelli has been associated with acrocyanosis and chilblains. Rarely, these lesions have progessed to cause ulceration and necrosis of the fingertips.

Treatment Options

Treatment options are summarized in Table I.

Table I.

Treatment options for angiokeratomas
Laser Therapy Surgical Procedures Local ablation
Nd:YAG Excision Cryotherapy
PDL Sclerotherapy Electrocautery
CO2
Copper vapor
Argon
KTP
PDL

Optimal Therapeutic Approach for Angiokeratomas Mibelli and Fordyce

Since angiokeratoma of Mibelli and Fordyce are benign lesions, they do not require treatment. However, patients may request treatment to improve cosmesis or to provide symptomatic relief of bleeding lesions. Treatment can be challenging when multiple lesions are present. Options for treatment include surgical excision, cryotherapy, electrocautery, sclerotherapy and laser therapy.

Treatment of angiokeratomas with excision is limited because the majority patients have multiple lesions, so it is impractical to excise them. However, if a single or few lesions are present, surgical excision may be a good option. Recurrences after local surgical excision with negative margins have been reported.

Locally destructive techniques, including electrocoagulation and cryotherapy, may also be used in patients with a limited number of lesions. Risks with these treatment modalities include hypopigmentation or hyperpigmentation, and scarring.

In patients with diffuse disease, laser therapy may be considered. A number of different lasers have been used, with variable success. The following lasers have been used in the treatment of angiokeratomas:

  1. Carbon dioxide laser: A patient with angiokeratoma of Mibelli who had previously been treated with 2 carbon dioxide laser treatments, which resulted in flattening of the lesions. However, they subsequently continued to progress, and atrophy was noted after treatment.

  2. Nd:YAG laser (1064 nm): A patient with diffuse angiokeratoma of Mibelli, previously treated with carbon dioxide laser, who was subsequently treated with 6 treatments of Nd:YAG laser under general anesthesia. The patient had good improvement, but atrophy and hyperpigmentation were noted. Nd:YAG in two patients with angiokeratoma of Fordyce (one scrotal and one vulvar) without the need for local anesthesia, with successful results after two treatments. Another 10 patients with angiokeratoma of Fordyce were treated with Nd:YAG laser, yielding moderate to complete response after two to six treatments. One patient developed an atrophic scar.

  3. Copper vapor laser (578 nm)

  4. Argon laser (578 nm)

  5. KTP Potassium-titanyl-phosphate laser (532 nm)

  6. Pulsed-dye laser (PDL) (585 nm): PDL use has been reported in 12 male patients with angiokeratoma of Fordyce. Between two and six sessions were performed. Good to excellent results were noted. Side effects included purpura, minimal swelling, bleeding and pain.

Ablative lasers, including carbon dioxide laser and Nd: YAG laser, may be the superior choice if marked hyperkeratosis is present, followed by a vascular laser if necessary. The data regarding treatment are based primarily on case reports in the literature. Further investigation is needed to determine which laser modality is the superior choice.

Sclerotherapy has also been reported in the treatment of angiokeratoma of Fordyce, utilizing 0.5% ethanolamine oleate and 0.25% sodium tetradecyl sulfate (STS), which resulted in flattened, smaller lesions. Side effects included mild temporary pain and epidermal sloughing.

Patient Management

Patients should be reassured regarding the benignity of these lesions. If treatment is desired, side effects of the proposed treatment modality should be discussed prior to the procedure.

Unusual Clinical Scenarios to Consider in Patient Management

Because thrombosed angiokeratomas can appear blue to black in appearance, they can clinically appear similar to malignant melanoma, resulting in preliminary misdiagnosis. As discussed, dermoscopy can be helpful in differentiating between the two diagnoses.

Angiokeratoma of Fordyce has been reported to occur after penectomy for penile cancer, emphasizing the importance of pathologic diagnosis to distinguish benign versus malignant neoplasms.

What is the Evidence?

Civas, E, Koc, E, Aksoy, B, Aksoy, HM. "Report of two angiokeratoma of Fordyce cases treated with 1064 nm long-pulsed Nd:YAG laser". Photodermatol Photoimmunol Photomed. vol. 25. 2009. pp. 166-8.

(Two cases of angiokeratoma of Fordyce (one scrotal and one vulvar) were treated with two treatments of Nd:YAG laser yielding successful results with minimal side effects.)

Lapidoth, M, Ad-el, D, David, M, Azaria, R. "Treatment of angiokeratoma of Fordyce with pulsed dye laser". Dermatol Surg. vol. 32. 2006. pp. 1147-1150.

(The authors studied the use of PDL in 12 patients with angiokeratoma of Fordyce as a nonablative laser treatment modality. Seven patients had an excellent response (75-100% clearance), and five patients had a good response (50-75% clearance).)

Malalasekara, AP, Goddard, JC, Terry, TR. "Angiokeratoma of Fordyce simulating recurrent penile cancer". Urology. vol. rwo69. 2007. pp. 576.e13-576.e14.

(This case report details the significance of histopathologic diagnosis of a patient with angiokeratoma of Fordyce presenting at the site of a penectomy for penile cancer.)

Ozdemir, M, Baysal, I, Engin, B, Ozdemir, S. "Treatment of Angiokeratoma of Fordyce with long-pulse Neodymium-Doper Yttrium Aluminum Garnet Laser". Dermatol Surg. vol. 35. 2009. pp. 92-7.

(Ten patients were treated with two to six sessions. Of the nine patients that completed the study, complete improvement was noted in one patient, significant improvement was noted in six patients and moderate improvement was noted in two patients.)

Pianezza, ML, Singh, D, van der Kwast, T, Jarvi, K. "Rare case of recurrent angiokeratoma of Fordyce on penile shaft". Urology. vol. 68. 2006. pp. 891.e1-891.e3.

(These authors report a case of angiokeratoma of Fordyce with two recurrences after surgical excision with negative margins.)

Requena, L, Sangueza, OP. "Cutaneous vascular anomalies. Part I. Hamartomas, malformations, and dilation of preexisting vessels". J Am Acad Dermatol. vol. 37. 1997. pp. 523-52.

(This is a comprehensive clinicopathologic review of vascular anomalies, hamartomas, malformations and dilations of preexisting vessels.)

Sahin, MT, Turel-Ermertcan, A, Ozturkan, S, Turkdogan, P. "Thrombosed solitary angiokeratoma simulating malignant melanoma: the importance of dermoscopy in differential diagnosis". J Eur Acad Dermatol Venereol. vol. 20. 2006. pp. 102-104.

(Sahin et al report a case of a solitary angiokeratoma of Mibelli that clinically resembled a nodular malignant melanoma. Dermoscopy and histology confirmed the diagnosis of angiokeratoma.)

Seo, SH, Chin, HW, Sung, HW. "Angiokeratoma of Fordyce treated with 0.5% ethanolamine oleate or 0.25% sodium tetradecyl sulfate". Dermatol Surg. vol. 36. 2010. pp. 1634-1637.

(The authors reported the use of sclerotherapy in the treatment of three patients with angiokeratomas of Fordyce. In each of the patients, there was significant improvement after one to two sessions of sclerotherapy. Responses were better to 5% ethanolamine oleate; however, 5% ethanolamine oleate was associated with more pain and sloughing.)

Sommer, S, Merchant, WJ, Sheehan-Dare, R. "Severly acral variant of angiokeratoma of Mibelli: Response to long-pulse Nd:YAG (1064 nm) laser treatment". J Am Acad Dermatol. vol. 45. 2001. pp. 764-6.

(This case report describes a 6-year-old female with widespread, congenital, keratotic vascular papules, determined to be consistent with angiokeratoma of Mibelli, that were treated with Nd:YAG laser.)
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