Anogenital Diseases

Introduction

• The anatomy ( Fig. 60.1 ), normal cutaneous findings, and benign lesions of the anogenital area ( Table 60.1 ) should be appreciated before addressing diseases in this area.

  
  Table 60.1

  Normal findings and benign lesions of the anogenital region.

  Papules in the anogenital region can also result from HPV infection, in particular condylomata acuminata and common warts (see Ch. 66 ).

  Common	Less common
  Epidermoid cysts	Fox–Fordyce disease
  Open comedones	Syringomas
  Pearly penile papules (see Fig. 95.7 )	Idiopathic calcinosis of the scrotum
  Vestibular papillomatosis	Urethral caruncle
  Angiokeratomas (see Fig. 94.11 )	Hidradenoma papilliferum
  Seborrheic keratoses and acrochordons
  Melanocytic nevi and genital lentigines (see Fig. 92.2 )
  Free sebaceous glands

• A number of systemic diseases affect the anogenital area ( Table 60.2 ).

  Table 60.2

  Systemic diseases that may present in the anogenital region.

  EM, erythema multiforme; SJS, Stevens–Johnson syndrome; TEN, toxic epidermal necrolysis.

  Inflammatory bowel disease, especially Crohn disease (see Ch. 45 ) Nutritional dermatoses, e.g. acrodermatitis enteropathica, necrolytic migratory erythema, cystic fibrosis (see Ch. 43 ) Langerhans cell histiocytosis (see Ch. 76 ) Kawasaki disease (see Ch. 3 ) Behçet disease – ulcers (see Ch. 45 ) Infections (nonvenereal), e.g. recurrent toxin-mediated perineal erythema, Fournier gangrene Infections (venereal) (see Ch. 69 ) Drug reactions (see Chapter 16 , Chapter 17 ), e.g. EM major, SJS, TEN; fixed drug eruption; toxic erythema of chemotherapy Neutrophilic dermatoses, e.g. Sweet syndrome (see Ch. 21 )

• Cutaneous disorders of the anogenital area may be more difficult to diagnose than those involving other cutaneous sites, as typical features may not be present.

• A number of dermatologic conditions affect the anogenital region, including inflammatory ( Table 60.3 ; Figs 60.2–60.6 ), bullous ( Table 60.4 ; Fig. 60.7 ), infectious ( Table 60.5 ; see Ch. 69 ), and premalignant and malignant conditions ( Table 60.6 ; Figs 60.8–60.11 ).

  Table 60.3

  Inflammatory disorders with anogenital features.

  Porokeratosis ptychotropica is a rare disorder and can mimic anogenital dermatitis or inverse psoriasis. The DDx of these disorders includes the other entities listed in this table; consider infections, either primary or superimposed (see Table 60.5 ); less commonly bullous disorders (see Table 60.4 ); if nonhealing consider malignancy, most commonly SCC (see Table 60.6 ).

  Inflammatory disorder	Anogenital features	Rx
  Anogenital dermatitis	Female > male Varied presentations, from mild erythema to significant lichenification ( Fig. 60.2 ) Unremitting itch/scratch cycle Female: perianal, labia majora, mons pubis Male: crura and scrotum	Examine entire body for clues to etiology (e.g. seborrheic or atopic dermatitis) Eliminate irritants/allergens Break itch/scratch cycle with potent topical CS for several weeks and then taper Oral antihistamines may help control pruritus Consider patch testing
  Psoriasis (including inverse psoriasis) (See Ch. 6 )	Perianal and intergluteal cleft fissuring; erythematous, smooth, well-demarcated plaques Female: labia majora and mons pubis Male : glans and shaft of penis ( Fig. 60.3 )	Mild–moderate Moderate potency topical CS for 2–3 weeks with taper to less potent topical CS plus antifungal Topical calcineurin inhibitors and vitamin D analogues (may sting) Severe (see Ch. 6 )
  Lichen sclerosus (LS)	See Fig. 60.4 and Ch. 36	See Ch. 36
  Lichen planus (LP) (see Ch. 9 )	Intense pruritus common in all forms	First-line Superpotent topical CS For vaginal disease, CS foams, enemas, suppositories or ointments (± dilators) Second-line Longer-term maintenance with superpotent topical CS or combined moderately potent CS/ antifungal/antibacterial preparations Topical calcineurin inhibitors Intralesional CS (hypertrophic) Systemic antimalarials (e.g. hydroxychloroquine) Systemic immunosuppressants (e.g. weekly methotrexate, mycophenolate mofetil) Systemic antibiotics (e.g. minocycline ± nicotinamide) Surgery to lyse adhesions
  1. Classic	Violaceous flat-topped papules and plaques; lacy white streaks Female: mons pubis and labia Male: glans and shaft of penis; often annular ( Fig. 60.5A )
  2. Erosive	Female > male Erosions surrounded by white lacy pattern; prominent scarring/adhesions ( Fig. 60.5B ) Desquamative vaginitis with discharge; significant pain and dyspareunia Usually severe oral involvement/desquamative gingivitis Increased risk for SCC
  3. Hypertrophic	Hyperkeratotic white plaques on the vulva or shaft of penis ( Fig. 60.5C ) Increased risk for SCC
  Zoon balanitis/vulvitis (plasma cell balanitis/vulvitis)	Male (uncircumcised) > female Pruritus and pain Male: glans penis ( Fig. 60.6 ) Erythematous discrete moist plaques with speckled appearance and orange hue Involvement of adjacent surfaces produce “kissing lesions” Female: similar lesions involving vulva	Circumcision curative Topical CS if symptoms

  
  
  
  
  
  Table 60.4

  Selected bullous disorders with anogenital features.

  Acquired autoimmune bullous diseases are clinically difficult to differentiate from one another and require biopsies for H&E and DIF, as well as serum for IIF and/or ELISA. MMP can be clinically indistinguishable from erosive lichen planus in the anogenital area. The DDx (especially of PV) may include other causes of erosions ( Table 60.7 ). Other blistering disorders, including LABD (linear IgA bullous dermatosis), epidermolysis bullosa acquisita (EBA), and paraneoplastic pemphigus can occur in the genital area (see Chapter 23 , Chapter 24 ). DIF, direct immunofluorescence; IIF, indirect immunofluorescence.

  Bullous disorder	Anogenital features	Rx
  Hailey–Hailey disease	See Ch. 48	See Ch. 48
  Bullous pemphigoid (BP) (See Ch. 24 )	Mostly affects the elderly, but a localized vulvar variant is occasionally seen in children A vegetans form favors flexural sites Less likely than PV to involve mucosal sites	Mild Potent topical/intralesional CS Severe Systemic CS Other systemic immunosuppressants Methotrexate (BP) Dapsone, cyclophosphamide (MMP) Dapsone or sulfapyridine (LABD) Mycophenolate mofetil, azathioprine (PV)
  Mucous membrane (cicatricial) pemphigoid (MMP) (See Ch. 24 )	External genitalia and anus Early : erosions, ulcerations, blisters ( Fig. 60.7 ) Pain, pruritus, dysuria Late : scarring prominent with related disability Phimosis, narrowing of vaginal introitus, anal stricture
  Pemphigus vulgaris (PV) (See Ch. 23 )	Vagina, labia, anus, penis Widespread erosions; vegetative and papillomatous nodulo-plaques may develop (pemphigus vegetans)	See Ch. 23

  
  Table 60.5

  Infectious (nonvenereal) disorders with anogenital features.

  Condylomata acuminata and venereal diseases are covered in Chapter 66 , Chapter 69 , respectively. The DDx of these disorders includes the other entities listed in this table; they may be confused with the disorders listed in Tables 60.2 and 60.3 as well as superimposed upon them; topical medications can also lead to a superimposed contact dermatitis.

  Infectious (nonvenereal) disorder	Anogenital features	Dx and DDx	Rx
  Candidiasis (See Ch. 64 and Figs 13.2 and 13.4 )	Favors the perianal area and inguinal crease, with sheet-like erythema, fissuring, erosions, and satellite pustules Female Vulvar erythema, small fissures Severe pruritus Creamy-white vaginal discharge Male Uncircumcised > circumcised Balanitis or balanoposthitis In the inguinal/scrotal folds, see erythema and focal white areas	Many anogenital diseases may be misdiagnosed as a “yeast” infection or develop superimposed candidiasis Confirm by microscopy (KOH preparation) and/or culture If pustules, consider impetigo	Address precipitating factors (e.g. diabetes mellitus, systemic antibiotics) Mild Topical antifungal/anti-yeast agents Vaginal anti-yeast suppositories Single, oral dose of fluconazole 150 mg (vaginal candidiasis) Severe Fluconazole 50–100 mg daily for 14 days Recurrent (>3 episodes/year) Treat sexual partners Oral fluconazole 150 mg weekly for 6 months Clotrimazole vaginal 500 mg tablets weekly for 6 months Oral itraconazole 200 mg, twice a day, once per month, for 6 months
  Dermatophytosis (tinea cruris) (See Ch. 64 and Fig. 13.2 )	Chronic, slowly advancing, scaly, erythematous patches and thin plaques; ± pustules Favors the groin (but scrotum often spared) with extension onto upper, medial thighs; medial buttocks Tinea pedis and toenail onychomycosis often present	Confirm with microscopy (KOH preparation)	Mild Topical antifungals Severe Oral terbinafine 250 mg daily for 2 weeks
  Erythrasma (See Ch. 61 and Fig. 13.2 )	Well-defined, pink to red-brown, pigmented patches or thin plaques with fine diffuse scale and wrinkling Favors flexural areas, such as groin and intergluteal cleft Caused by Corynebacterium minutissimum	Wood’s lamp examination (coral pink fluorescence)	Mild Antibacterial soaps Topical 10–20% aluminum chloride Topical 2% clindamycin, erythromycin Severe Oral erythromycin for 5 days
  Perianal and vulvovaginal streptococcal infection (See Ch. 61 and Fig. 13.4 )	Children >> adults Sharply demarcated, bright perianal erythema, extending 2–3 cm around the anal verge Painful defecation or urination Blood-streaked stools Irritation or pruritus Caused by group A β-hemolytic Streptococcus May also involve the neck and inguinal regions, especially in children (streptococcal intertrigo) May be preceded or accompanied by pharyngitis	Diagnosis made with bacterial culture or rapid strep test of involved site Also consider: candidiasis, irritant contact dermatitis, pinworm infection, child abuse, and early Kawasaki disease (if inguinal) May trigger guttate psoriasis	Oral cephalosporin, penicillin or erythromycin for 10–14 days Follow with re-culture to exclude recurrence

  Table 60.6

  Premalignant and malignant disorders with anogenital features.

  Multiple biopsies may be necessary to make a diagnosis. The DDx of these disorders includes the other entities listed in this table and Table 60.2 , as well as seborrheic keratosis, condylomata acuminata, NMSC, and amelanotic melanoma.

  Premalignant and malignant disorders	Anogenital features	Other	Rx
  Premalignant lesions
  Vulvar intraepithelial neoplasia (VIN) Penile intraepithelial neoplasia (PIN) Perianal intraepithelial neoplasia (PaIN) Anal intraepithelial neoplasia (AIN)	Varied presentations Erythematous or pigmented, well-demarcated plaque (genital Bowen disease variant) Verrucous white-gray plaque Erosions Nonhealing ulcer Erythematous, shiny, velvety patch or plaque (erythroplasia of Queyrat variant) ( Fig. 60.8 )	Several etiologies/ predisposing factors Oncogenic HPV (e.g. subtypes 16, 18, 31, 33) Inflammatory, scarring conditions (e.g. lichen sclerosus, erosive lichen planus) Uncircumcised male Immunosuppression HIV infection	In conjunction with gynecologic or urologic oncologist Long-term evaluation necessary, including anal and cervical cytology Examine sexual partners Varies from topical agents (e.g. imiquimod, 5-fluorouracil) to surgical excision, including Mohs surgery Prevention: HPV vaccination
  Bowenoid papulosis	See Fig. 60.9 and Ch. 66	See Ch. 66	See Ch. 66
  Malignant lesions
  Invasive SCC	Varied presentations Nonhealing ulcer or fissure Erythematous plaque with heaped-up edges ( Fig. 60.10 ) Verrucous plaque Nodule	Most common anogenital tumor, but overall rare Etiologies are similar to those listed for premalignant lesions	Consult with gynecologic or urologic oncologist First-line: surgical excision, including Mohs surgery Second-line: XRT
  Extramammary Paget disease	Slowly expanding erythematous plaque with demarcation between normal and involved skin; erosions and scale present ( Fig. 60.11 ) Favors vulva and perianal regions Pruritus, burning, or asymptomatic	Rare intraepithelial adenocarcinoma More common in older females and Japanese males May be primary or secondary to an underlying malignancy Associated underlying visceral malignancy in 10–20% Associated underlying adnexal adenocarcinoma in <5%	Initial and periodic systemic evaluations for internal malignancy are necessary Surgical excision vs. Mohs surgery Combination therapy, e.g. topicals (see above), XRT, photodynamic therapy

  Table 60.7

  Causes of genital erosions and ulcerations.

  Lichen sclerosus (see Fig. 36.9 B) Erosive lichen planus (see Fig. 60.5B ) Genital aphthae/aphthosis ∗

  Infection – Candidiasis (see Figs 13.2 and 13.4 ) – Impetigo ( Staphylococcus/Streptococcus ) – Herpes simplex viral infection (see Figs 67.2 E and 67.6D) or herpes zoster – Primary syphilis, chancroid – Epstein–Barr virus (EBV; Fig. 60.15 ) ∗∗ , † , cytomegalovirus † , Mycoplasma † – Tuberculosis

  Squamous cell carcinoma and other malignancies Intraepithelial neoplasia

  Zoon plasma cell balanitis/vulvitis (see Fig. 60.6 )

  Acquired bullous diseases – Pemphigus vulgaris – Bullous pemphigoid – Mucous membrane (cicatricial) pemphigoid (see Fig. 60.7 ) – Linear IgA bullous dermatosis – Epidermolysis bullosa acquisita – Erythema multiforme, Stevens–Johnson syndrome (see Fig. 16.7 B) – Fixed drug eruption (see Fig. 17.10 B) Inherited bullous disease – Hailey–Hailey disease (see Fig. 13.2 ) – Epidermolysis bullosa

  Complex aphthosis due to Behçet disease or inflammatory bowel disease Crohn disease (see Fig. 13.2 ) Extramammary Paget disease (see Fig. 60.11 ) Langerhans cell histiocytosis (see Fig. 76.1 ) Necrolytic migratory erythema, acrodermatitis enteropathica (see Fig. 43.9 ) Papular acantholytic dyskeratosis Toxic erythema of chemotherapy (see Fig. 17.15 A)

  ∗ Includes reactive non-sexually related acute genital ulcers, which can be triggered by a variety of viral and bacterial infections.

  ∗∗ Diagnosed via EBV IgM antibodies or PCR; favors female children and adolescents.

  † Cause/trigger of reactive non-sexually related acute genital ulcers.

  
  
  
  

• Pain and pruritus can be the presenting symptoms in a wide variety of anogenital diseases ( Figs 60.12 and 60.13 ).

  
  

• Patients with anogenital disease should use soap substitutes and bland emollient ointments; irritants and potential allergens (e.g. flushable moist wipes, previous topical medications) should be avoided.

• Ointments are preferred over creams in this area because of less irritation and burning with application, as well as providing a better barrier to urine and feces.

• The anogenital region is an area of occlusion and more prone to adverse side effects from and increased absorption of topical agents (e.g. CS).

• High-potency topical CS are generally avoided because of the increased risk for atrophy and striae, but they are used with confidence in certain situations (e.g. lichen sclerosus, erosive lichen planus) for periods of up to 12 weeks once to twice yearly.

• Because of increased moisture, warmth, and occlusion, anogenital diseases have an increased risk of superimposed bacterial and fungal infections.

• Diseases that result in scarring of the anogenital region (e.g. lichen sclerosus, erosive lichen planus) carry an increased long-term risk of developing invasive SCC.