Bowen disease is a rare chronic atypical slowly progressive epithelial proliferation in-situ squamous cell carcinoma (SCC) of epidermis skin disorder characterized by multiple well-demarcated red-brown to violaceous papules in the genital area. The major etiological factors of BD include ultraviolet light exposure, immunosuppression, and Human Papilloma Virus (HPV) infections. Affected individuals develop a slow-growing, reddish scaly patch or plaque on the skin. Sun-exposed areas of the skin are most often affected. Bowen’s disease only affects the outermost layer of the skin (epidermis). Lesions are usually not painful or may not be associated with any symptoms (asymptomatic). In most cases, treatment is highly successful. Bowen disease is considered a pre-cancerous condition, although the risk of developing skin cancer is less than 10 percent. The disorder usually affects older adults. The exact cause of Bowen’s disease is unknown, although there are identified risk factors such as chronic sun exposure.
Bowen’s disease was first described in the medical literature by a physician named JT Bowen in 1912. Bowen disease is also known as squamous cell carcinoma in situ and is generally considered an early, noninvasive form of intraepidermal squamous cell carcinoma. Intraepidermal means that the disease occurs inside the epidermal layer of the skin.
Types
BD of genitalia
The SCC in-situ of the penis is eponymously termed Erythroplasia of Queyrat and Bowen’s disease. Though both are pathologically the same process, the term EQ is used for lesions over mucosal surfaces such as inner prepuce, glans, and urethra. The term BD is used when the skin of the shaft of the penis is affected. BD of penis presents as well-defined, single, dull-red scaly plaques often with crusting and pigmentary changes. BD has also been reported to arise from the inguinal and suprapubic areas. EQ is painless, very well-demarcated, bright-red, velvety, shiny, plaque-like appearance[rx,rx]
Perianal BD
The perianal BD is more common among women.[rx] Perianal BD has minor symptoms such as itching or burning sensation. Around one-third of the patients complain of a bleeding lesion or mass.[rx] In anogenital BD, various morphological forms such as nodular, pigmented, verrucous, ulcerated, leukoplakic, and polypoidal have been described in the literature. In the anogenital region, the mean size at the time of biopsy is around 1.3 cm2.[rx] The risk of invasive carcinoma is 2%–6% in this entity.[rx]
Periungual BD
Periungual BD is more common in men, usually observed in the first three digits of the left hand. It clinically manifests as flat, erythematous patches with slight scaling to crusted verrucous lesions.[rx] It can also manifest as hyperkeratotic, papillomatous, or warty proliferations, scaling or erosions of the nail fold, whitish cuticle, periungual swelling, paronychia, fissuring or ulceration of the lateral nail groove, in-grown nails, granulation-like tissue beneath, partial loss of the nail plate, onycholysis, and nail dystrophy. Pseudo-Hutchinson sign, longitudinal melanonychia, or erythromycin have been observed in nail BD.[rx,rx,rx] The pseudo-fibrokeratoma associated with melanocytic pigmentation serves as a diagnostic clue in nail BD.[rx] Polydactylous BD is a rare nail BD subtype.[rx] In the case of Fanconi’s anemia, multiple fingers with multicentricity have been reported.[rx] The HPV-associated periungual BD has put forward the genital digital spread as a probable mechanism of tumor induction.[rx]
Palmar BD
BD of palms is often associated with arsenicosis and presents with expanding diameter, fissuring, and frictional hypertrophy.[rx,rx] Ulceration can occur secondary to repeated friction.[rx]
Facial BD
BD of the face manifests as broad patches of faint erythema with minimal scaling or with a typical appearance of solar keratosis with bright red erythema and an adherent, yellow, keratotic scale.[rx] The involvement of the eccrine gland in BD is not common, usually confined to the temple region.[rx]
Mucosal BD
Grossly mucosal lesions have one of these three appearances: i) erythroplasia-like, ii) nodular or papillomatous, and iii) ulcerative. These morphological lesions correlate with three pathological stages proportionate to the age of the tumor, the severity of infiltration, and degeneration.[rx] It can also present as a velvety reddish plaque.[rx]
Nipple BD
Even though BD is intraepidermal, the uniqueness of nipple anatomy paves way for the tumor to spread via lactiferous ducts as it is in continuation with the nipple epidermal layer. The nipple BD can present either as a raised, pruritic, scaly plaque or as an eczematous lesion with crusting, bleeding, or ulceration.[rx]
Pigmented BD
Pigmented BD is a rare subtype constituting less than 2% of BD. It presents clinically as a well-defined, hyperpigmented, flat, or verrucous plaque with a velvety surface.[rx] It is more commonly seen in genital and interdigital areas but also reported in sites such as lips, digits, and umbilicus.[rx] The cause for pigmentation in this variant is due to increased melanocyte hyperplasia with hypertrophic dendritic processes, the presence of well-differentiated atypical keratinocytes, or due to specific cytokines and growth factors produced by tumor cells.[rx] The verrucous BD is a rare subtype, which often incites the suspicion of invasive malignancy.[rx]
Symptoms
Typically, Bowen’s disease appears as a slow-growing, persistent reddish-brown patch or plaque of dry, scaly skin. These lesions may be flat or slightly raised. The lesions are normally not associated with any symptoms, but, occasionally, can itch, ooze pus (if infected), bleed, or become crusted and/or tender. In some cases, the lesions may be warty (verrucous), split open (fissured), or, less often, darkly colored (pigmented). In most cases, there is only one lesion, but in approximately 10-20 percent of individuals, multiple lesions may develop usually in more than one area of the body.
Although Bowen’s disease occurs most often in sun-exposed areas of the skin, it can develop anywhere on the body, even in areas of the skin that are not usually exposed to the sun. The disorder most often develops on the lower legs. Less commonly, the head, neck, palms, soles, and genitals can be affected. The lesions can measure anywhere from a few millimeters to a few centimeters.
Individuals with Bowen disease are at risk of developing skin cancer. The risk is estimated to be less than 10 percent but can be higher in individuals with a compromised immune system. Early signs of cancerous transformation in Bowen disease include the development of a fleshy nodule or bump in a skin lesion. This nodule may be tender and bleed easily. Ulceration or hardening (induration) of a skin lesion also indicates malignant transformation.
The morphology of BD differs based on the age of the lesion, site of origin, and degree of keratinization.[rx] In places where keratinization is absent, lesions are erythematous and velvety. This erythema is masked by scaling in lesions occurring over keratinized epithelium.[rx] The clinical presentation is also altered when it occurs on intertriginous, moist, or hyperkeratotic surfaces.[rx] Lesions are usually solitary, whereas multiple lesions are seen in 10%–20% of the affected individuals. In the case of multicentric BD, immunosuppression and arsenicosis should be considered.[rx,rx]
The classical lesions of BD are asymptomatic, while larger lesions can be pruritic. Most commonly BD presents as a slow-growing, well-demarcated, erythematous, scaly patch or plaque [rx]. Classical BD is associated with some degree of redness, ranging from pink to bright salmon-red erythema. The overlying scale may be white or yellow in color and rupial in nature, which can be easily removed or adherent. The removal of scale does not produce any bleeding and reveals an erythematous wet surface.[rx] The scale may be very well pronounced mimicking psoriasis.[rx]
Bowen disease is classified as an early, noninvasive form of squamous cell carcinoma, a type of skin cancer that most often occurs on sun-damaged areas of the skin. Squamous cell carcinoma is the second most common form of skin cancer.
Causes
The exact cause of Bowen’s disease is unknown. Chronic sun exposure and aging are believed to be two major risk factors for developing the disorder. Individuals with fair skin and individuals who spend a lot of time outdoors in the sun are at a greater risk of developing Bowen disease. Individuals who take drugs to suppress the immune system (usually taken to treat an immune system disorder) are also at a greater risk than the general population of developing Bowen disease.
The etiology of BD is multifactorial. The risk factors include Caucasian race, fair skin, photo-sensitive individuals, and an increase in total occupational and recreational sun exposure.[rx] The cumulative exposure to ultraviolet light radiation produces DNA damage and immunosuppression facilitating the clonal expansion of underlying p53 mutation.[rx,rx]
Patients with allogeneic organ transplantation on immunosuppressive drugs such as systemic corticosteroids, azathioprine, and cyclosporine may activate different pathways resulting in the induction and promotion of skin malignancies.[rx] In immunosuppressed patients, Merkel cell polyomavirus has been associated.[rx]
The BD arising secondary to arsenic exposure is known to occur after several decades.[rx] Arsenic exposures produce oxidative stress and deplete antioxidants. It causes immune dysregulation, impaired DNA repair, genotoxicity, and disorganized signal transduction.[rx]
BD is also known to arise following ionizing radiation, thermal skin injury, inflammatory dermatoses such as chronic lupus erythematosus, lupus vulgaris, and following Psoralens and Ultraviolet-A radiation.[rx,rx,rx] BD has been reported in a person who was involved in arc welding.[rx] The incidence of aneuploidy and DNA instability is high in lesional skin of BD.[rx,rx] summarize the etiopathogenesis model of BD.
Individuals who have cutaneous human papillomavirus (HPV) infection are at risk of developing Bowen disease. Human papillomaviruses are a group of more than 150 related viruses, some of which can cause cancer. HPV 16, 18, 34, and 48 have caused Bowen’s disease at genital sites. HPV 16 is most commonly associated with the development of Bowen’s disease. HPV 16 is also the cause of some cases of cervical cancer. Less often, HPV types 2, 16, 34, and 35 are associated with Bowen’s disease in areas of the body other than the genitals. In BD, several subtypes of the Human Papilloma Virus such as HPV 16, 18, 31, 33, 35, 54, 58, 61, 62, and 73 have been detected.[rx] A strong association with HPV 16 had been reported with vulvar BD.[rx] HPV DNA is observed in 31% of the extragenital BD.[rx] HPV 16, 31/33, 56, and 71 have been detected by in-situ hybridization in nail BD.[rx]
Chronic exposure to arsenic appears to be a risk factor for the development of Bowen disease as well. Arsenic is a tasteless, colorless metal element. Arsenic has many uses in manufacturing and other commercial uses. According to the medical literature, chronic exposure to arsenic can cause Bowen disease, approximately 10 years or so after initial exposure. In the past, arsenic was known to have contaminated well water and was once used in various medicinal preparations. Arsenic exposure occurs far less often today than it did in the past.
Risk factors for intraepidermal SCC include:
- Sun exposure: intraepidermal SCC is most often found in sun-damaged individuals.
- Arsenic ingestion: intraepidermal SCC is common in populations exposed to arsenic.
- Ionizing radiation: intraepidermal SCC was common on the unprotected hands of radiologists early in the 20th century.
- Human papillomavirus (HPV) infection: this is implicated in intraepidermal SCC on fingers and fingernails.
- Immune suppression – due to disease (eg chronic lymphocytic leukemia) or medicines (eg azathioprine, cyclosporin).
- Up to 50% of patients with intraepidermal SCC have other keratinocyte skin cancers, mainly basal cell carcinoma.
Diagnosis
A diagnosis of Bowen’s disease is suspected based upon the identification of characteristic symptoms, detailed patient history, and a thorough clinical evaluation. The disorder is easily mistaken for other skin disorders such as eczema or psoriasis and can be overlooked because there may be no associated symptoms. Bowen’s disease may sometimes first be noticed during a routine skin examination.
Immunohistochemistry
In BD, the keratinocyte nuclei for proliferating cell nuclear antigen (PCNA) have a diffuse pattern of staining. The CK10 is widely expressed in all cases of BD. The p16 staining is helpful in differentiating different histological variants of BD. The p16 overexpression reflects the disrupted nature of the G1/S checkpoint leading to uncontrolled cell cycle progression.[rx,rx] Ki-67 expression shows a diffuse pattern of staining of atypical keratinocytes in BD differentiating it from actinic keratosis.[rx] The BD histopathological specimen shows positive immunostaining for lumican.[rx] Pagetoid BD expresses CK7, the specific marker of Paget’s disease. The CK14 expression may be a marker of tumor progression.[rx] BD of nipple clinicopathologically mimics Paget’s disease, but stains positive for cytokeratin 5/6 and negative for cytokeratin 7.[rx]
Dermoscopy
There are no standard dermoscopic criteria mentioned in the literature for the diagnosis of BD.[rx] Zalaudek et al.[rx] first described dermoscopic features such as glomerular vessels and scaly plaques in BD, glomerular vessels correlate with dilated papillary dermal vasculature histopathologically. The commonly observed features are scaly surface, small brown globules with patchy distribution, homogenous grey brownish, and reticular pigmentation.[rx]
Payapvipapong and Tanaka published a classification regarding three different types of BD. They include
- 1) Classic BD – Atypical vascular pattern, whitish scale, and a pinkish network;
- 2) Pigmented BD – pigmentation without structure, pigmented stripes, and crusts;
- 3) Partially pigmented BD – Combination of the above two.[rx]
The dermoscopic differential diagnoses are actinic keratosis, seborrheic keratosis, basal cell carcinoma, lichen planus-like keratosis, mammary Paget’s disease, and lentigo malignant melanoma.[rx]
Reflectance confocal microscopy
Reflectance confocal microscopy is an ancillary tool, which enables in the differentiation of pigmented BD from other pigmented lesions. The findings suggestive of pigmented BD are polygonal, refractile structures in upper layers, atypical honeycomb pattern, targetoid cells, different size and shaped atypical keratinocytes, and “button-hole signs” homogenous with tortuous blood vessels.[rx,rx]
The electron microscopic examination of BD demonstrates many dyskeratotic cells surrounded by perinuclear aggregation and condensation of tonofilaments.[rx] Phasor fluorescence lifetime imaging microscopy (FLIM) is a newer, simple tool that provides rapid confirmation of BD.[rx]
Clinical Testing and Work-Up
Diagnosis of Bowen’s disease may be confirmed by a biopsy of the affected tissue. With a biopsy, a sample of affected tissue is removed and studied under a microscope. A biopsy can help to differentiate Bowen’s disease from other skin disorders with a similar appearance. The sample taken must be deep enough to rule out invasive squamous cell carcinoma.
Treatment
The treatment depends on various factors like the site, size, immune status, patient’s age, esthetic outcome, etc. The available therapeutic modalities include topical chemotherapy, surgical modalities, light-based modalities, and destructive therapies. It requires a combined effort of dermatologists, surgeons, and plastic surgeons to plan and execute the management in various presentations of BD.
A wide variety of treatment options exist for individuals with Bowen disease including topical chemotherapy, cryotherapy, curettage, photodynamic therapy, and surgery. Most therapies have an excellent response rate and the prognosis of Bowen disease in most cases is excellent. The response to a particular therapy may vary – what works for one person may be less effective in another. A treatment plan for Bowen’s disease will be tailored to a patient based on what is best for his or her case.
Topical chemotherapy involves the application of creams applied directly to the lesion. Two common topical medications used to treat Bowen disease are 5-fluorouracil and imiquimod 5%. These treatments may be used alone or in conjunction with other therapies. 5-fluorouracil works by destroying abnormal skin cells. Generally, affected individuals apply the cream once or twice daily for at least two weeks if not much longer.
Imiquimod 5% is generally used for lesions on the lower legs, larger lesions, and the erythroplasia of the Queyrat variant of Bowen disease. The nonconventional therapies such as a combination of oral cyclooxygenase enzyme inhibitor and topical imiquimod, topical tazarotene, topical diclofenac, topical paricalcitol, phenol peel, topical and intralesional bleomycin, oral acitretin, oral isoretinoin with subcutaneous interferon-alpha and ultrasonic surgical aspiration have been useful.[rx,rx]
Topical chemotherapy
Imiquimod
This immune response modifier has antitumor activity by stimulating the local production of cytokines.[rx] Imiquimod is a good treatment option for BD lesions of difficult-to-treat areas like the lower leg, shaft, glans penis, and large facial lesions. The clinical efficacy varies between 57% and 86% after 6 weeks in various trials. Imiquimod has been reported to be used in conjunction with 5-fluorouracil and sulindac in immunosuppressed individuals.[rx] Sotiriou et al.[rx] treated a large BD measuring 100 cm2 with a single session of MAL-PDT along with daily topical imiquimod for 6 weeks. The associated inflammatory reaction, erythema, and pigmentation are the commonly reported adverse effects. It has limited efficacy in hyperkeratotic BD.[rx,rx] In a study, 38% (6/16) of the patients discontinued the imiquimod used earlier due to its side effects.[rx]
Fluorouracil
This topical cytotoxic agent is used in the treatment of BD on the skin, and shaft of the penis as a once or twice daily application for 3–4 weeks, to be repeated if needed.[rx,rx] Clinical evidence showed a complete clinical response in 48% to 83% of individuals with daily use for 3–4 weeks.[rx] The efficacy of 5-FU can be increased by application under occlusion, pretreatment with laser, iontophoresis, and with the use of dinitrochlorobenzene as a vehicle.[rx] The pain, erythema, burning sensation, and ulceration at the applied site are the common adverse effects associated with its use.[rx]
Light-based procedures
Photodynamic therapy
Photodynamic therapy (PDT) for BD involves topical application of Methyl Amino-levulinate (MAL) under occlusion for three hours followed by illumination using red light from a narrowband light-emitting diode source. It is repeated once after 7 days and again 3 months later if needed. The use of fluorescence helps in lesion delineation and recurrence detection with 100% sensitivity and 85% specificity.[rx] It is of immense benefit in large lesions (>3 cm2), leg BD, and in difficult-to-treat sites. Topical PDT is noninvasive, tissue sparing, highly efficacious, and a good esthetic therapeutic modality.[rx,rx] There are case reports of successful treatment of BD with PDT in the setting of radiodermatitis and epidermolysis bullosa.[rx]
Radiotherapy
The various radiotherapy techniques used in the treatment of BD are external beam radiotherapy, radioactive skin patch, and Grenz rays.[rx] In BD, both high and low-dose regimens of radiotherapy are equally efficacious in the treatment.[rx] The advantages of this technique include utilization in difficult-to-treat areas such as the scalp, penile, and perianal BD. The disadvantages include high cost, patient inconvenience, and poor wound healing in the legs.[rx,rx,rx]
Lasers
LASERS are considered for genital and nail lesions.[rx] In a large retrospective study, 44 BD patients were treated with CO2 laser achieving clearance in 86% of patients after one treatment.[rx] Because CO2 laser spares the deeper follicular epithelium, chances of recurrence and treatment failure are high. To overcome this, a diode laser can be used as a final pass following the three passes of the CO2 laser.[rx]
Surgical modalities
Excision
Simple wide excision of the lesion and primary closure is an acceptable method of treating BD of small size, single lesion, and perianal BD. It is helpful by histopathologically ruling out the invasive disease.[rx, RX,rx] The BD is excised with a minimum of 4 mm margin in well-defined tumors of <2 cm in diameter and at least 6 mm margin for larger lesions or less-differentiated tumors or lesions in high-risk locations (e.g., scalp, eyelids, ears, nose, and lips).[rx] Excision with a narrow lateral margin may lead to subclinical lateral spread, which is associated with a higher chance of recurrence.[rx] The recurrence rate varies from 2.8% to 19.4% in various studies. The limitations are prolonged wound healing in certain regions and functional and cosmetic outcomes.[rx,rx,rx]
Moh’s micrographic surgery
Moh’s micrographic surgery is very effective in difficult-to-treat areas like periorificial, periungual regions and genital lesions where tissue sparing is the main objective.[rx] It is also useful in incompletely excised and recurrent BD. In a retrospective analysis of 270 cases of BD in the head and neck region treated with Moh’s micrographic surgery, 128 cases were previously treated with modalities such as cryotherapy, curettage and cautery, excision, and radiotherapy.[rx] The recurrence after Moh’s surgery is around 6.3%.[rx]
Destructive modalities
The involvement of pilosebaceous units by atypical epithelium can lead to failure of treatment when superficial destructive modalities are used.[rx]
Curettage with cautery
It is a simple, cheap, safe, and one of the most effective treatment modalities suitable in single, small BD.[rx,rx] It is preferred in patients who have large hyperkeratotic lesions, are intolerant to cryotherapy, and cannot apply topical agents for a prolonged period.[rx] However, the results depend on the equipment used and the skill of the operator. The cure rate ranges from 81% for curettage and up to 93% to 98% in case of curettage and cautery.[rx,rx]
Cryotherapy
Cryotherapy is a simple, inexpensive, outpatient modality of treatment of BD. It is used as a treatment modality in the case of single, small BD located at well healing sites.[rx] The efficacy of cryotherapy differs depending on the technique and regimens used. It is avoided in poorly vascularized areas and legs where wound healing is prolonged. The failure rate is around 5%–10%.[rx,rx,rx,rx] Gaitanis et al.[rx] successfully treated four cases of BD in renal transplant recipients with cryotherapy and topical imiquimod for 2 weeks with no recurrence.
Superficial skin surgery
Superficial skin surgery refers to shave, curettage and electrosurgery, and is an excellent choice for solitary or few hyperkeratotic lesions. The lesion is sliced off or scraped out; then the base is cauterized. Dressings are applied to the open wound to encourage moist wound healing over the next few weeks.
Fluorouracil cream
5-fluorouracil cream contains a cytotoxic agent and can be applied to multiple lesions. The cream may be used for intraepidermal SCC for four weeks and repeated if necessary. It causes a vigorous skin reaction that may ulcerate.
Imiquimod cream
Imiquimod cream is an immune response modifier used off-license to treat intraepidermal SCC. It is applied 3–5 times weekly for 4–16 weeks and causes an inflammatory reaction.
Summary of various treatment modalities of Bowen’s disease
| Drug | Application | Preferred | Limitations and adverse effects | Outcome |
|---|---|---|---|---|
| Imiquimod 5% cream | Once-daily application for 16 weeks | Large lesions, face, lower leg, the shaft of penis, glans penis | Limited response in hyperkeratotic lesions, erythema, inflammation, crusting, pigmentation | 57%-86% clearance |
| 5-Fluorouracil cream | Once- or twice-daily application for 3-4 weeks, repeated if required | Large lesions, poor healing sites | Cannot be used in immunocompromised patients, pain, erythema, burning sensation, ulceration | 48%-83% clearance |
| Cryotherapy | Freeze of 30 s at least once or 20 s at least twice for one to three sittings | Good healing sites Multiple lesions | Cannot be used in poor wound healing sites, Hypopigmented scarring | 68%-100% clearance 5%-10% failure rate |
| Curettage with cautery | Simple, single-time, safe method | Small/single lesion, facial lesions | Cannot be performed for larger lesions, Success depends on the skills of the operator | 93%-98% cure rate 2%-20% recurrence |
| Excision | Simple, wide excision of the lesion | Small/single lesion with poor healing | Prolonged wound healing, poor functional and cosmetic outcomes | 2.8% to 19.4% recurrence |
| Moh’s micrographic surgery | Individual layers of tissue are removed and examined under a microscope | Tissue sparing sites such as periorificial, genital, and periungual regions | Expensive needs a skilled operator | Recurrence is around 6.3% |
| Photodynamic therapy | Day 0, 7, and repeated after 1 month | For larger lesions and difficult-to-treat areas | Pain | 88%-100% clearance 3 months after one cycle of MAL-PDT |
| Radiotherapy | Both high- and low-dose regimens are equally efficacious | Difficult-to-treat sites such as digits and penis | High-cost, patient inconvenience, poor healing, erythema, edema | Failure to heal in 33% of individuals |
| LASERS | CO2 LASER | Difficult-to-treat sits such as digits and penis | Spares deeper follicular epithelium | Clearance of 86% after one treatment |
Investigational Therapies
Various case reports in the medical literature discuss the use of laser therapy for the treatment of Bowen’s disease. In individual patients, laser therapy has been effective in treating the disorder. However, no clinical trials in large populations have been undertaken. In addition, laser therapy may be expensive and have limited availability. More research is necessary to determine the long-term safety, effectiveness, and viability of laser therapy as a potential treatment for Bowen’s disease.
Clinical differential diagnoses of Bowen’s disease
| Cutaneous erythematous BD |
| Actinic keratosis |
| Amelanotic melanoma |
| Basal cell carcinoma |
| Clear cell acanthoma |
| Discoid lupus erythematosus |
| Irritated or inflamed seborrheic keratosis |
| Lichen simplex chronicus |
| Lichen planus |
| Nummular eczema |
| Psoriasis |
| Seborrheic eczema |
| Squamous cell carcinoma |
| Warts |
| Pigmented BD |
| Blue naevi |
| Bowenoid papulosis |
| Lichen planus-like keratosis |
| Melanocytic Naevi |
| Melanoma |
| Pigmented actinic keratosis |
| Pigmented basal cell carcinoma |
| Seborrheic keratosis |
| Solar lentigo |
| Verrucous BD |
| Hypertrophic lichen planus |
| Seborrheic keratosis |
| Verruca Vulgaris |
| Verrucous carcinoma |
| Nail BD |
| Amelanotic malignant melanoma |
| Finger eczema |
| Glomus tumor |
| Nail dystrophy |
| Nail lichen planus |
| Onychomycosis |
| Paronychia |
| Periungual wart |
| Psoriasis |
| Pyogenic granuloma |
| Subungual exostosis |
| Subungual keratoacanthoma |
| Squamous cell carcinoma |
| Verrucous tuberculosis |
| Nipple BD |
| Paget’s disease |
| Erythroplasia of Queyrat |
| Candidiasis |
| Erosive lichen planus |
| Extramammary Paget’s disease |
| Fixed drug eruption |
| Lichen sclerosis |
| Penile psoriasis |
| Zoon’s balanitis |
| Perianal BD |
| Condyloma acuminata |
| External hemorrhoids |
| Monilial infections |
| Papillomas |
References
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