Cutaneous Tuberculosis

Etiology

CTB is caused by infection with the Mtb complex. Rarely, CTB can be caused by the attenuated strain of Mycobacterium bovis and the BCG vaccine.[2] See StatPearls companion resource, “Tuberculosis Overview,” for more information on the microbiology and etiology of tuberculosis.

Epidemiology

TB remains a global concern, infecting approximately 10 million people annually. Worldwide, TB is the leading cause of death from a single infectious disease, according to the World Health Organization (WHO).[WHO/tuberculosis] Most cases are concentrated in endemic areas, with India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh, and the Democratic Republic of the Congo accounting for more than two-thirds of global cases.[3] Consequently, endemic areas have higher rates of CTB, which represents about 1% to 3% of extrapulmonary tuberculosis. The incidence of disease is notably higher (approximately 6%) in parts of the world where infection with HIV is prevalent.[3]

Pathophysiology

Cutaneous forms of TB can develop from direct inoculation of the skin, contiguous spread from infected lymph nodes and organs to the skin, or hematogenous dissemination to the skin. CTB can also develop in the form of hypersensitivity reactions to Mtb antigens. As noted earlier, the clinical presentation of CTB is a function of the route of infection in conjunction with Mtb strain pathogenicity, prior exposure, and immune status of the host.[3][2][1][6] See StatPearls companion resource, “Tuberculosis Overview,” for more information on pulmonary and extrapulmonary TB pathophysiology.

Direct inoculation can result in tuberculous chancre in those without prior exposure and in TB verrucosa cutis or lupus vulgaris in those with some degree of TB immunity. Hematogenous dissemination can cause acute miliary CTB or TB gumma in the immune-compromised host and lupus vulgaris in those with some degree of TB immunity. Contiguous spread from lymph nodes, bones, and other organs can cause scrofuloderma or lupus vulgaris. Autoinoculation of mucosal tissues resulting in TB orificialis can occur in immune-compromised hosts with TB involving the gastrointestinal, respiratory, and genitourinary tracts. Tuberculids are considered type IV hypersensitivity reactions to Mtb antigens and infer that there is an underlying focus of active pulmonary or extrapulmonary TB.[7] The precise immunopathogenesis underlying CTB clinical presentations is complex and not fully elucidated. 

Histopathology

The classic histopathological finding of CTB is the presence of tuberculoid granuloma. However, early lesions may present as a suppurative reaction characterized by a dense dermal infiltrate of neutrophils, lymphocytes, and plasma cells. Over time, a homogeneous eosinophilic necrotic center develops, with multinucleated giant cells palisading the caseation. Stains, eg, Ziehl-Neelsen, Fite-Faraco, Kinyoun, and Auramine-rhodamine, aid in determining the presence of acid-fast bacilli. The histopathological findings differ depending on the specific form of CTB. However, characteristic histology may be absent in up to 30% of cases.[6] The following findings may be demonstrated with these CTB manifestations:

• Tuberculous chancre: At the inoculation site the early stages demonstrate a suppurative infiltrate of neutrophils. Dermal necrosis may be present in the reticular dermis. Granulomas may develop in later stages. AFB stains are usually positive.

• TB verrucosa cutis: Pseudoepitheliomatous hyperplasia with hyperkeratosis is seen with microabscesses composed of neutrophils in the papillary dermis. Granulomas within the mid-dermis are often present. AFB stains are usually negative.

• Lupus vulgaris: Granulomas, whether tuberculoid or confluent, with central caseous necrosis, present in a quarter of cases. Granulomas can be surrounded by lymphocytes and plasma cells. Changes to the epidermis vary from acanthosis to hyperkeratosis. AFB stains are usually negative.

• Scrofuloderma: Tuberculoid granulomas have been a feature in all cases. Necrosis, giant cells, and neutrophilic abscesses are commonly present. AFB stains are usually positive.

• Orificial TB: The epidermal changes vary from ulceration to acanthosis. Caseating granulomas are commonly present. AFB stains are usually positive.

• Acute miliary TB: Similar to lupus vulgaris, the epidermal changes in acute miliary TB vary from hyperkeratosis to acanthosis or papillomatosis. Neutrophilic abscesses can be found in the dermis, where chronic inflammatory cells consist of lymphohistiocytic and plasma cell infiltrates. Necrosis is a common feature. AFB stains are usually positive.

• Tuberculous gumma: Granuloma may or may not form; however, diffuse histiocytic infiltrate is present. Casseation typically occurs in the reticular dermis. AFB stains are usually positive.

• Lichen scrofulosorum: The papillary dermis contains perifollicular granulomas. Caseation is absent. AFB stains are negative.

• Papulonecrotic tuberculid: Leukocytoclastic vasculitis and vascular occlusion are present in association with necrosis within the papillary dermis. Granulomas are rare. AFB stains are negative.

• Erythema induratum of Bazin: Lobular panniculitis, lymphocytic vasculitis, and fat necrosis in the presence or absence of epithelioid granuloma. AFB stains are negative.

History and Physical

The diagnosis of CTB requires vigilance and a high index of suspicion since its clinical presentation can mimic many inflammatory and neoplastic diseases. In areas of the world where TB prevalence is low, CTB is exceedingly rare and easily overlooked. A thorough history should include TB and HIV risk factors, country of origin, family history and known TB exposure, history of TB, BCG vaccination, occupational exposure, and localized trauma. 

Since CTB can coexist with pulmonary and other extrapulmonary forms of TB, both history and physical examination should explore these possible manifestations. Systemic symptoms, eg, fever, malaise, anorexia, weight loss, and night sweats, occur in approximately 30% of cases.[1] Lymphadenopathy due to disseminated TB is common and should be explored during the physical examination. In addition to lymph nodes, TB-infected bones, joints, and epididymis may underlie lesions of scrofuloderma. 

Tuberculous chancre

Tuberculous chancre (also known as primary inoculation tuberculosis) accounts for up to 1% of CTB. It typically presents as a red to brown papule that develops 2 to 4 weeks after mycobacteria enter the injury site. Over time, the lesion ulcerates, forming undermined borders. Chancres are generally painless. (see Image. Tuberculous Chancre).

Tuberculous verrucosa cutis

TB verrucosa cutis accounts for 3% to 19% of CTB cases. As the name suggests, it presents as a verrucous plaque. These lesions are usually found on the lower legs and feet, often due to kneeling on contaminated surfaces or walking barefoot. TB verrucosa cutis is typically diagnosed years after the initial injury because the lesion grows slowly and remains asymptomatic. (see Image. Tuberculosis Verrucosa Cutis).

Lupus vulgaris

Lupus vulgaris is the most common form of CTB, accounting for about 63% of cases. It can result from endogenous as well as exogenous sources of infection. In the latter case, inoculation via localized trauma, eg, ear piercing or placement of a tattoo by contaminated instruments, can result in lupus vulgaris lesions. Like TB verrucosa cutis, lupus vulgaris is slow-growing and asymptomatic, which leads to delayed diagnosis. The typical presentation is a red to brown plaque, with one border showing a scaly crust and the other showing scarring. The center of the lesions is often atrophic. Multiple plaques may arise and are typically found on the head, neck, arms, or legs. They can appear in a sporotrichoid pattern, where lesions spread along the lymphatic channels in a linear configuration. (see Image. Lupus Vulgaris Pretreatment and Posttreatment).

Scrofuloderma

Scrofuloderma is most common in endemic areas of developing countries such as Brazil and India. It most commonly presents in children as asymptomatic, indurated plaques that later ulcerate and drain purulent or caseous material. The ulcers often have violaceous borders. Scrofuloderma can present as a solitary lesion or multiple lesions, typically overlying cervical lymph nodes. It may also appear in other areas of infected lymph nodes and overlying infected bones, joints, and the scrotum. (see Image. Scrofuloderma Involving Bilateral Cervical Lymph Nodes).

Orificial tuberculosis

Orificial TB is a rare form of CTB that presents as a painful ulcer that does not heal. Due to self-inoculation in those with pulmonary TB or gastrointestinal involvement, this form is more commonly found in the oral cavity of immunosuppressed individuals. It can also occur in the nares, vulva, and peri-anal mucosa (see Image. Orificial Tuberculosis).

Miliary tuberculosis

Acute cutaneous miliary TB is a rare form but has the highest mortality rate. Individuals with this form of CTB often appear ill and present with multiple red papules and pustules that vary in size. Some papules can be umbilicated, and others may have necrotic centers. These lesions are commonly found on the trunk and extremities. There is an association with HIV/AIDS and other causes of immune suppression. (see Image. Miliary Cutaneous Tuberculosis).

Tuberculous gumma

Tuberculous gumma, also known as metastatic tuberculous abscess, is another rare form of CTB, typically seen in immunosuppressed individuals. It presents as multiple subcutaneous nodules that can ulcerate and develop sinus tracts. It is associated with a high mortality rate (see Image. Tuberculous Abscess).

BCG vaccination reactions and tuberculid lesions

BCG vaccination frequently causes a mild, localized, temporary skin reaction at the injection site. Abscess, chancre, fistula, and lupus vulgaris can rarely occur. Disseminated CTB has been rarely reported after BCG vaccination. The immunocompromised host is at the highest risk of this rare complication (see Image. Bacillus Calmette-Guérin Scar and Lymph Nodal Abscess and Progression).[4]

Tuberculid forms are due to a hypersensitivity reaction to Mtb antigens. Lichen scrofulosorum is seen most commonly in the pediatric population. It can present as perifollicular papules and coalescing lichenoid papules and plaques, often in a bilateral and symmetrical pattern on the trunk and lower extremities. It can also occur as a complication of BCG-associated lupus vulgaris.[4] Papulonecrotic tuberculid appears as painless, necrotic red-brown to violaceous papules and ulcers overlying extensor surfaces and develop most often on the trunk and extremities. Erythema induratum of Bazin presents as tender, erythematous subcutaneous nodules often appearing on the legs. The lesions can progress to ulcerate. It occurs predominantly in young women (see Images. Papulonecrotic Tuberculid and Erythema Induratum of Bazin in a 48-Year-Old Female).

Evaluation

When CTB is suspected, the following tests should be obtained: 

• Skin biopsy with culture, histology, nucleic acid amplification test (NAAT), and AFB stain
• If scrofuloderma is suspected, a fine needle aspiration cytology along with stains, NAAT, and culture
• Interferon Gamma Release Assay (IGRA), particularly in those having received BCG vaccine or TB skin test if IGRA is not available
  • A negative test does not preclude a diagnosis of CTB
  • A positive test supports but does not confirm a diagnosis
• Complete blood count, metabolic panel, erythrocyte sedimentation rate
• HIV antibody test
• Focused screening tests for pulmonary and extrapulmonary TB, including chest x-ray, ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI) scan

See StatPearls companion resource, “Tuberculosis Overview,” for more information on the diagnosis of TB.

Treatment / Management

Anti-tuberculosis therapy (ATT) for CTB is the same as for active pulmonary and extrapulmonary TB. A standard 4-drug regimen consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol is administered for the first 2 months of intensive phase therapy. This is followed by a continuation phase of between 4 and 12 months with isoniazid and rifampin. The aforementioned assumes the presence of drug-sensitive TB. In the case of drug resistance, the ATT regimens require modifications in the agents and the duration of therapy.[1][6][4][8] See StatPearls companion resource, “Tuberculosis Overview,” for more information on the treatment of drug-sensitive and resistant TB. When clinicians have a strong clinical suspicion of CTB, and definitive results of stains, cultures, NAAT, and histology are not available, initiating a course of ATT is reasonable.[1] Most cases of CTB will show evidence of a response within 4 to 6 weeks.

The outcome of treatment for CTB depends on several factors, including the individual’s immune status, overall health, the stage of the disease, the type of cutaneous lesions, treatment adherence, duration of therapy, and any adverse effects experienced during treatment. Regarding the latter, the initiation of ATT requires close monitoring of potential adverse effects and drug interactions. See StatPearls companion resource, “Tuberculosis Overview,” for more information on ATT adverse effects and drug interactions.

Differential Diagnosis

The differential diagnoses of CTB are extensive. A complete list is beyond the scope of this activity; however, several excellent reviews are available on this topic.[1][3][4] Bacterial, fungal, parasitic, and other mycobacterial infections, neoplasia, autoimmune diseases, and drug eruption are conditions that can have similar presentation to CTB. The differential diagnoses also include:

• Syphilitic chancre
• Secondary syphilis
• Bacterial abscess
• Sporotrichosis
• Blastomycosis
• Nocardiosis
• Leishmaniasis
• Actinomycosis
• Sarcoid
• Psoriasis
• Discoid lupus
• Hidradenitis
• Squamous cell carcinoma
• Drug eruption

Prognosis

Overall, the prognosis of CTB is generally better than in individuals with internal organ involvement or immunocompromised individuals. However, even with aggressive treatment, the outcome may be poor in immunocompromised patients or those harboring drug-resistant organisms. Among the different forms of CTB, mortality rates are higher in tuberculous gumma (approximately 66%) and miliary CTB, with mortality rates reaching up to 75%.[6] Additionally, scarring is a common complication of healed CTB lesions. If untreated, lupus vulgaris can eventually undergo malignant transformation to squamous carcinoma.[6]