Papulonecrotic Tuberculids 

Updated: Jun 19, 2018
Author: Manuel Valdebran, MD; Chief Editor: William D James, MD 

Overview

Background

The term tuberculid was first described by Darier in 1896.[1] Subsequently, in 1936, Pautrier established the diagnosis of papulonecrotic tuberculid as a distinct tuberculosis-associated disorder.

Although many types of tuberculids have been described, most are now understood to not be uniquely caused by tuberculosis. However, papulonecrotic tuberculids (PNTs) and lichen scrofulosorum are still widely accepted as true tuberculids.

Papulonecrotic tuberculid is a chronic, recurrent, and symmetric eruption of necrotizing skin papules arising in crops, involving primarily the buttocks and extensor surfaces of the arms and legs.[2] A hallmark of this condition is that lesions heal with varioliform and pitting scarring. The eruption is believed to represent a hypersensitivity reaction to tuberculosis antigens released from a distant focus of infection. Most patients react markedly to the Mantoux skin test (purified protein derivative [PPD]), may exhibit other evidence of current or past tuberculosis infection, and react quickly to antituberculous therapy.[3, 4]

Pathophysiology

The pathophysiology of papulonecrotic tuberculid is controversial. Most authors believe this disease entity is triggered by an initial Arthus reaction to mycobacterial antigens. This is then followed by a hypersensitivity reaction in which antigens undergo opsonization by antibodies, followed by immune complex deposition in small cutaneous blood vessels. The ensuing complement cascade triggers a leukocytoclastic vasculitis, leading to destruction of vessel walls with ensuing tissue necrosis. Over time, this type III hypersensitivity reaction may be replaced by a type IV reaction. Other authors dispute this mechanism, citing the lack of leukocytoclastic vasculitis in some cases. Instead, they propose that the primary lesion is the result of subacute lymphohistiocytic vasculitis that leads to thrombosis and subsequent tissue necrosis.

A consensus has been reached that papulonecrotic tuberculid represents a true hypersensitivity reaction rather than the result of a local cutaneous tuberculosis infection. This is based on the observation that papulonecrotic tuberculid lesions have consistently failed to either stain positive for, or culture out, mycobacterial organisms. Although the organisms are absent, mycobacterial DNA has been detected in approximately half of the biopsy specimens subjected to polymerase chain reaction (PCR).[3, 5] These observations support the idea that lesions of papulonecrotic tuberculid are the result of released mycobacterial antigens in the setting of a concurrent but distant infection.

Etiology

The eruption is a form of an exaggerated host immunologic response to a mycobacterial infection involving the cutaneous vessels. Active tuberculosis is reported in as many as 40-75% of patients,[6] most commonly in lymph nodes. Polymerase chain reaction (PCR) amplification for mycobacteria varies. In a series of 12 cases in India, PCR positivity was found in 25% of the cases.[5]

Epidemiology

Frequency

United States

A decreasing incidence of papulonecrotic tuberculid began in the second half of the 1900s and the decline continues to this day. This phenomenon is attributed to aggressive tuberculosis control now found in wide practice. Currently, almost all cases come from areas outside of North America with high endemic rates of tuberculosis.[7] Historically, reports indicate that young women and children are especially susceptible to this disorder.[2]

Papulonecrotic tuberculid–like lesions have also been associated with other mycobacterial infections, including Mycobacterium bovis and Mycobacterium kansasii, and from BCG vaccination.[8]

International

Papulonecrotic tuberculid is an uncommon disorder even in populations with a high prevalence of tuberculosis, occurring in less than 5% of active tuberculosis cases. In the literature, 91 cases were reported during a 17-year period in South Africa in 1974. In addition, 12 cases from a period of longer than 30 years in England were reported in 1986. In the latter study, most patients were immigrants and had presumably acquired the infection outside of England. The incidence of tuberculosis is expected to rise as the influx of refugees from endemic areas like Africa and the Middle East continues to grow.[9] Freiman et al reported a case in a 25-year-old woman from the Philippines who had immigrated to Canada 8 years previously.[10] In a 9-year period, 4 cases were reported in Hong Kong, which was the least common of the cutaneous tuberculosis presenting during that time.[11] In a 5-year period, 12 cases were reported in India, a country that has the highest burden of tuberculosis in the world.[5, 12]

Sex

Females seem to be at a slightly increased risk for developing this disorder.

Age

Children and young adults are more susceptible to this condition than other people. Papulonecrotic tuberculids represent 4% of pediatric skin tuberculosis.[5] In a 1974 study from South Africa, two thirds of the patients were younger than 30 years.

Prognosis

Without treatment, patients typically follow a waxing and waning course lasting many years, although spontaneous resolution has been reported.

Papulonecrotic tuberculids respond promptly to appropriate antituberculosis therapy. New lesions cease forming within days to weeks after therapy is initiated, and existing lesions heal rapidly, usually within weeks. Recurrences are rare after appropriate therapy.

 Significant varioliform or pitted scarring is a sequela, and progression to lupus vulgaris has been observed.[13, 14] An association with Takayasu arteritis of the aortic arch has also been documented.[15]

 

Presentation

History

Papulonecrotic tuberculids present as papules, nodules, or pustules, which may become ulcerated and crusted. They arise in a symmetric fashion with a predilection for the extremities, particularly the upper limbs. Although described as affecting extensor surfaces, widespread involvement may be present.[5]

Lesions heal spontaneously within weeks; those ulcerated leave a varioliform scar.

New lesions form as older lesions resolve, giving the eruption a polymorphous appearance.

Oral lesions have not been reported to date.

Papulonecrotic tuberculids have been reported to coexist with lesions of erythema induratum,[16] as well as lichen scrofulosorum.[17] In several reports, cutaneous lesions resolved with appropriate antituberculosis therapy.

Physical Examination

Primary lesion

The characteristic initial lesions are 2- to 8-mm, erythematous papules that become pustules and undergo central ulceration forming hemorrhagic-crusted papules. See the image below.

Bilaterally symmetric papulonecrotic lesions on th Bilaterally symmetric papulonecrotic lesions on the lower extremities.

Distribution

Lesions arise in symmetric crops, typically with an acral predilection. Characteristically, lesions develop over the extensor surfaces, particularly the knees, the elbows, and the dorsum of the hands and the feet, although widespread involvement may occur. Involvement of the glans penis has rarely been reported.

Color

Hyperpigmented to erythematous papules with central crusting are seen early, and the lesions generally heal with scarring.

Lymph nodes

In one study, as many as one third of the cases were associated with cervical lymphadenopathy, and some patients developed scrofuloderma.

Complications

Complications include significant varioliform scarring and those associated with tuberculosis infections, including progression to lupus vulgaris.

 

DDx

Diagnostic Considerations

Also consider the following:

  • Pityriasis lichenoides et varioliformis acuta (PLEVA)
  • Septicemia
  • Perforating granuloma annulare
  • Miliary tuberculosis (patients are ill and lesions are culture-positive for tuberculosis)
  • Suppurative folliculitis
  • Pustular syphilide

Differential Diagnoses

 

Workup

Laboratory Studies

Patients should be evaluated for evidence of active tuberculosis or other forms of mycobacterial infection. Tuberculous involvement of the female genital tract may account for the increased incidence in females, and a culture of menstrual fluid and endometrial biopsy may be of value in excluding occult disease.

CBC count, chemistry panel, and urinalysis should be performed.

The erythrocyte sedimentation rate is often very high and can be used to monitor treatment. It decreases 4-6 weeks after treatment is started.

Imaging Studies

Chest radiography is needed to rule out active or past pulmonary tuberculosis. Abdominal radiographs may show lymph node calcifications typical of tuberculosis.

Other Tests

Purified protein derivative (PPD) intradermal skin tests are usually strongly positive. Some authors require this result for diagnosis. However, false-negative negative results can occur in the setting of immunosuppression.

QuantiFERON®-TB Gold test can also be used to confirm latent tuberculosis infection, avoiding the risk of severe skin reactions that may occur with PPD testing.[19, 20]

Histologic Findings

The histologic features vary with the timing of the biopsy. In an early lesion, evidence of a vasculitis, which is typically leukocytoclastic with fibrinoid necrosis of the vessel wall and karyorrhectic debris, should be present. However, some authors have found that the primary lesion consists of lymphohistiocytic, rather than leukocytoclastic, vasculitis. It has been reported as a constant finding in a series of cases with the presence of a psoriasiform epidermal hyperplasia, as well as the presence of superficial and deep mixed inflammatory infiltrate including neutrophils and eosinophils.[5]

Characteristic of the disorder is the presence of perivascular spongy edema. Because of the obliterative vascular changes, a wedge-shaped area of dermal necrosis develops, surrounded by a granulomatous inflammatory infiltrate with giant cells and epithelioid histiocytes. Well-formed tuberculoid granulomas with Langerhans giant cells are not usually present in the lesions. Special stains for mycobacteria are typically negative.

The histologic differential diagnosis depends on the timing of the biopsy as well as the histologic appearance. In particular, inflammatory palisading granulomas (ie, granuloma annulare and infectious granulomas) may look similar as compared to those found occasionally in papulonecrotic tuberculid. However, the ability to exclude mucin and infectious organisms in effect rules out granuloma annulare and infectious granulomas, respectively.[21]

See the images below.

Papulonecrotic tuberculid. Multinucleated giant ce Papulonecrotic tuberculid. Multinucleated giant cells are noted within the granulomas. Courtesy of Prof Oscar Tellechea, MD, and José Carlos Cardoso, MD.
Papulonecrotic tuberculid. Higher magnification sh Papulonecrotic tuberculid. Higher magnification shows better detail of the area of necrosis surrounded by a granulomatous process. Courtesy of Prof Oscar Tellechea, MD, and José Carlos Cardoso, MD.
 

Treatment

Medical Care

Treatment is directed at eradicating the underlying mycobacterial infection. Tuberculosis treatment guidelines may vary from region to region and from different authorities (ie, the World Health Organization [WHO] and the Centers for Disease Control and Prevention [CDC]). Currently, for patients with active tuberculosis, a 4-drug therapy with rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) is recommended to avoid the development of resistance. Papulonecrotic tuberculids respond promptly to appropriate antituberculosis therapy. New lesions cease forming within days to weeks after therapy is initiated, and existing lesions heal rapidly, usually within weeks. A minimum of 6 months of antituberculosis therapy is recommended. Recurrences rarely occur after appropriate therapy.

Also see the Medscape Drugs & Diseases articles Tuberculosis and Tuberculosis Organism-Specific Therapy, as well as the World Health Organization guidelines, Recommendations for Investigating Contacts of Persons with Infectious Tuberculosis in Low- and Middle-Income Countries.[22]

 

Medication

Medication Summary

The goal of pharmacotherapy is to eradicate the underlying mycobacterial infection that causes papulonecrotic tuberculid.

Antitubercular agents

Class Summary

These agents are effective in the treatment of mycobacterial infections. Therapy with a 4-drug combination of rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) is recommended to avoid the development of resistance.

Isoniazid (Laniazid, Nydrazid)

Isoniazid is the best combination of effectiveness, low cost, and minor adverse effects. It is a first-line drug unless resistance or another contraindication is known. Therapeutic regimens of less than 6 months demonstrate an unacceptably high relapse rate. Coadministration of pyridoxine is recommended to minimize the risk of peripheral neuropathy secondary to isoniazid therapy. Prophylactic doses of 6-50 mg of pyridoxine daily are recommended. Twice-weekly dosing is not recommended in HIV patients with CD4 lymphocyte counts of less than 100 cells/µL.

Rifampin (Rifadin, Rimactane)

Rifampin is for use in combination with at least one other anti-TB drug. It inhibits DNA-dependent bacterial RNA polymerase but not mammalian RNA polymerase. Cross-resistance may occur. Treat for 6-9 months or until 6 months have elapsed from conversion to sputum culture negativity.

Pyrazinamide

Pyrazinamide is a pyrazine analog of nicotinamide that may be bacteriostatic or bactericidal against M tuberculosis, depending on the concentration of the drug attained at the site of infection; its mechanism of action is unknown. Administer for the initial 2 months of a 6-month or longer treatment regimen for drug-susceptible patients. Treat drug-resistant patients with individualized regimens.

Ethambutol (Myambutol)

Ethambutol diffuses into actively growing mycobacterial cells, such as tubercle bacilli. It impairs cell metabolism by inhibiting the synthesis of one or more metabolites, which, in turn, causes cell death. No cross-resistance is demonstrated. Mycobacterial resistance is frequent with previous therapy. Use ethambutol in these patients in combination with second-line drugs that have not been previously administered. Administer daily until permanent bacteriologic conversion and maximal clinical improvement is seen. Absorption is not significantly altered by food.