In 1896, John Addison Fordyce first described angiokeratomas of Fordyce on the scrotum of a 60-year-old man. Angiokeratomas are typically asymptomatic, 2- to 5-mm, blue-to-red papules with a scaly surface located on the scrotum, shaft of penis, labia majora, inner thigh, or lower abdomen. Histologically, they are composed of ectatic thin-walled vessels in the superficial dermis with overlying epidermal hyperplasia.[2, 3, 4, 5]
Precise data on their frequency and distribution are lacking, although estimations have been made. The principal morbidity comes from bleeding, anxiety, and overtreatment due to misdiagnosis by physicians. Usually, they do not require treatment. If treatment is needed, then locally destructive methods including laser, electrocoagulation, excision, cryotherapy, or laser therapy may be used.[2, 6]
Angiokeratoma is a broad term that describes various conditions of asymptomatic hyperkeratotic vascular disorders with a histologic combination of hyperkeratosis and superficial dermal vascular ectasia. More specifically, angiokeratomas can be categorized into localized and systemic forms.
The localized forms include (1) solitary papular angiokeratoma, which typically occurs on the legs; (2) localized angiokeratoma of the scrotum and vulva (Fordyce type); (3) the congenital form, angiokeratoma circumscriptum naviforme, which presents as multiple, hyperkeratotic, papular and plaquelike lesions, usually unilaterally on the lower leg, foot, thigh, buttock, and occasionally elsewhere; and (4) bilateral angiokeratomas that occur on the dorsa of the fingers and toes (Mibelli type).
The generalized systemic form, angiokeratoma corporis diffusum, is usually associated with a metabolic disorder, the most common being Fabry disease or fucosidosis. Even though Fabry disease is associated with the generalized presentation, a case report in 2010 recommends considering Fabry disease in all male patients with angiokeratomas, even if localized to the scrotum. Although the pathogenesis and clinical presentation vary, the histologic features are similar for all forms.[2, 9, 10]
The pathophysiology of angiokeratomas remains unknown, although increased venous pressure may contribute to their formation.
Many reports describe angiokeratomas occurring in the presence of a varicocele or other conditions of increased venous pressure (eg, hernias, epididymal tumors, urinary system tumors, trauma, and thrombophlebitis). Other causative factors include acute or chronic trauma and nevoid or vascular malformations. One series reports that up to two thirds of patients have associated conditions. One report describes treatment of the varicocele followed by resolution of the angiokeratomas, and another report describes varicocele treatment followed by no improvement in the angiokeratomas.
Many cases have been described in which no cause for increased venous pressure was found. In a study of 435 military recruits aged 18-19 years, 10% (n = 46) were found to have varicoceles; none had angiokeratomas. They also surveyed 30 soldiers aged 45-55 years with varicoceles but found no angiokeratomas. They propose that the coexistence of varicocele and angiokeratomas is coincidental. Similarly, a study of 1552 Japanese males found no history of any venous obstructive disorders.
In a study of vulval angiokeratomas, 54% of patients were noted to have a predisposing factor (eg, pregnancy, vulval varicosity, post partum, post hysterectomy), while the rest had none.
Penile and vulvar angiokeratomas have also been noted status post radiation treatment of genitourinary malignancy. A 2006 report describes a man with a recurrent penile angiokeratoma after surgery. Another author describes angiokeratoma of Fordyce simulating penile cancer. Angiokeratomas have been described on the clitoris in a 14-year-old girl, as well as in conjunction with chronic infection with human papillomavirus in a 25-year-old woman.
Angiokeratomas of Fordyce have also been reported in association with nevus lipomatosus, oral mucosal angiokeratomas,[9, 22] and papular xanthoma.
Interestingly, a case of a 16-year-old boy with congenital lymphangiectasia-lymphedema born to consanguineous parents was found to have angiokeratoma of the scrotum and the penis at an early age.
The precise incidence of angiokeratomas of Fordyce is unknown, but they are considered common, especially with increasing age.[2, 3, 4]
No fatalities have been reported from this condition. The most significant morbidity comes from bleeding. The papules can bleed spontaneously if traumatized or during intercourse. Many of the reports describe patient concern that the lesions represent a sexually transmitted disease.
Large series of angiokeratomas have been reported from America and Japan, which give a picture of disease predominantly in whites and in Japanese populations. Cases in blacks exist but are few in number.
Males have been reported far more often than females, although direct figures of comparison do not exist. Some suggest that female angiokeratoma cases are probably as common as male cases but are grossly underreported and underrepresented in the literature.
Cases have been reported, ranging from children born with lesions to lesions developing in patients in their sixth decade. The only publication on vulval lesions, identified by pathology reports of removed lesions, showed that 68% of lesions occurred in women aged 20-40 years. A study of 1552 Japanese males found that angiokeratomas occurred at all ages but were most prevalent among people older than 40 years. Prevalence was as follows :
Patients usually give a history of many years of a progressive appearance of asymptomatic papules on the scrotum. The patient may not be aware of the lesions, and bleeding (spontaneous, after intercourse or scratching) may be the first presentation causing the patient to seek medical help.[2, 6]
Many cases are reported in which help was sought to rule out a sexually transmitted disease or to rule out malignancy.[5, 18, 25]
Bleeding from vulval lesions may occur spontaneously, during pregnancy, or after intercourse.
Most authors report that lesions are asymptomatic; however, a few describe pain or itching.
Fordyce angiokeratomas appear as black, blue, or dark red, dome-shaped papules ranging from 1-6 mm in diameter, with a mean of 3 mm. The overlying surface may show slight scales (hyperkeratosis).
Reports suggest that in younger patients, the lesions tend to be smaller, more erythematous, and less hyperkeratotic. Older patients have larger, darker lesions (blue/black) with overlying scales.
The lesions number from 1 to multiple. In a study of 25 women with vulval lesions, 50% of the cases had solitary lesions.
Lesions have been reported on the labia majora, shaft of the penis, corona of the glans penis, inner thigh, and lower abdomen. The scrotum is the most common site.[31, 32]
See the images below.
Image courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.
Close-up of the eruption. Image courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.
The role of coexistent venous hypertension, varicocele, or status post radiotherapy remains uncertain and warrants further investigation.
Imaging studies are not warranted in the evaluation of angiokeratomas.
Dermoscopy can assist with the diagnosis. Angiokeratoma is characterized by large, well-demarcated, round-to-oval, and red-to-black areas, which are lacunar. In addition, a white surrounding veil corresponds to the acanthotic and hyperkeratotic epidermis.
If the diagnosis is in doubt, then a skin biopsy is recommended.
Numerous dilated, thin-walled vessels are positioned in the papillary dermis or superficial submucosa, with an intimate relationship to the overlying acanthotic epidermis with overlying parakeratosis. In addition to elongation of the rete ridges, the epithelium is usually hyperkeratotic. Thrombosis of the vascular spaces is common, and, frequently, recanalization of occluded vascular spaces occurs, creating the pathologic pattern known as papillary endothelial hyperplasia (Masson lesion).
The importance of these lesions was well summarized by Bean, "These varicules should be known so that we can allay the fears of old men, many of whom have worries enough already." If the lesions are an incidental finding or are asymptomatic, the patient can be reassured about the lesions’ benign nature. If concern exists regarding bleeding or cosmetic appearance, then several surgical treatment options are available.
his is not practical if more than a few lesions exist. However, excision can be performed with the patient under local anesthesia, with a good cosmetic result.[2, 3, 4, 28, 33, 34] Obtaining negative margins has been recommended by authors who have treated recurrent angiokeratomas of the scrotum.
Application of liquid nitrogen has been used with resolution of diffuse patterns, but with residual hypopigmentation and scarring.
Light electrocoagulation has been used with or without local anesthesia to produce effective resolution of diffuse lesions.[2, 3, 4, 28, 33, 34]
Successful resolution has been reported with single treatments using both the 578-nm copper laser and the argon laser, resulting in minimal scarring.
A 2004 study showed benefit using a 532-nm potassium-titanyl-phosphate (KTP) laser. Another study in 2006 evaluated the efficacy of pulsed-dye laser in 12 patients with scrotal angiokeratomas. The results demonstrated good-to-excellent response in all patients, with transient purpura and minimal procedural bleeding as the only adverse effects.
In 2009, a study has shown long pulse 1-64 Nd:YAG laser to be effective, with at least 65-100% improvement in 10 patients and only 1 who had had a long-term adverse effect of an atrophic scar.
A second study published in 2009 also using long-pulse 1064-nm Nd:YAG laser described 2 cases (one of the scrotum, one of the vulva) treated successfully with no recurrence in a 2-year and 6-month follow-up, respectively.
In addition, ablative lasers such as carbon dioxide and erbium-doped yttrium aluminium garnet lasers have been used to remove the hyperkeratotic epidermis before treatment with a vascular laser.[38, 39]
A 2010 article reported 3 cases treated successfully with repeated local injections of 0.5% ethanolamine oleate or 0.25% sodium tetradecyl sulfate. Both therapies had minimal and temporary adverse effects, including mild pain and epithelial sloughing with no scarring.
Consult a dermatologist if the diagnosis is in doubt; alternatively, a biopsy can be performed on the lesions and can be submitted to a dermatopathology laboratory for microscopic diagnosis.
Consult a urologist if suspicion of a varicocele is present.
Angiokeratomas of Fordyce are a benign neoplasms and are not amenable to drug therapy.[2, 3, 28, 33, 34]
If a surgical procedure is performed, follow-up care at 3 months post treatment is indicated to assess the cosmetic result and to look for recurrences.
As mentioned previously, bleeding is the only major complication that angiokeratoma patients experience.
Spontaneous resolution is not described. The angiokeratomas persist unless treated. Patients with multiple angiokeratomas are more likely to have recurrences after treatment than those with few or solitary angiokeratomas.