You are in: eMedicine Specialties > Dermatology > MYCOBACTERIAL INFECTIONS Papulonecrotic TuberculidsArticle Last Updated: Jan 26, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Robert L Chen, MD, PhD, Instructor, Department of Medicine, Section of Dermatology, University of Chicago Medical Center Robert L Chen is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Dermatology Foundation, and Society for Investigative Dermatology Coauthor(s): David Barnette, Jr, MD, Chief of Dermatopathology, Departments of Internal Medicine and Dermatology, Naval Medical Center at San Diego Editors: Terry L Barrett, MD, Director, Associate Professor, Department of Dermatology, Division of Dermatopathology and Oral Pathology, Johns Hopkins University School of Medicine; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System Author and Editor Disclosure Synonyms and related keywords: PNT, necrotizing skin papules, tuberculosis hypersensitivity, TB antigens INTRODUCTIONSection 2 of 10
  BackgroundThe tuberculids, first described by Darier in 1896, represent a form of cutaneous hypersensitivity reaction to tuberculosis (TB) antigens. Although many types of tuberculids have been described, most are now understood to not be uniquely caused by TB. However, papulonecrotic tuberculids (PNTs) and lichen scrofulosorum are still widely accepted as true tuberculids. The entity PNT was first established by Pautrier in 1936 as a distinct TB-associated disorder, when he described the characteristic clinical and histopathologic features. PNT is a chronic, recurrent, and symmetric eruption of necrotizing skin papules arising in crops, involving primarily the arms and the legs. A hallmark of this condition is that lesions heal with varioliform scarring. The eruption is believed to represent a hypersensitivity reaction to TB antigens released from a distant focus of infection. Most patients react markedly to the Mantoux skin test (purified protein derivative, PPD) and may exhibit other evidence of current or past TB infection. PathophysiologyThe pathophysiology of PNT 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. However, 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. Whatever underlies the pathophysiology, a consensus has been reached that PNT represents a true hypersensitivity reaction rather than the result of a local cutaneous TB infection. This is based on the observation that PNT lesions have consistently failed to either stain positive for, or culture out, mycobacterial organisms. Although the organisms are absent, mycobacterial DNA have been detected in approximately half of the biopsy specimens subjected to polymerase chain reaction. These observations support the idea that lesions of PNT are the result of released mycobacterial antigens in the setting of a concurrent but distant infection. FrequencyUnited StatesA decreasing incidence of PNT began in the second half of the 1900s and the decline continues to this day. This phenomenon is attributed to aggressive TB control now found in wide practice. Currently, almost all cases come from areas outside of North America with high endemic rates of TB. However, a rare US case, involving a previously healthy 9-year-old girl from Chicago, Ill, was reported in 1990. Historically, reports indicate that young women and children are especially susceptible to this disorder. PNT-like lesions have also been associated with other mycobacterial infections, including Mycobacterium bovis and Mycobacterium kansasii, and from BCG vaccination. With the increased incidence of TB infection in patients with HIV, the frequency of PNT may increase, although this has not yet occurred, due possibly to effective public health measures to identify, isolate, and treat active cases of TB. InternationalPNT is an uncommon disorder even in populations with a high prevalence of TB, occurring in less than 5% of active TB 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. Mortality/MorbidityThe condition typically follows a prolonged and relapsing course lasting years, although spontaneous resolution has been reported. Significant varioliform scarring is a sequela, and progression to lupus vulgaris has been observed. An association with Takayasu arteritis of the aortic arch has also been documented. SexFemales seem to be at a slightly increased risk for developing this disorder. AgeChildren and young adults are more susceptible to this condition than other people. In the 1974 study from South Africa, two thirds of the patients were younger than 30 years. CLINICALSection 3 of 10
History
Physical
CausesThe eruption is a form of an exaggerated host immunologic response to a mycobacterial infection involving the cutaneous vessels. Active TB is reported in as many as 40% of patients. DIFFERENTIALSSection 4 of 10
Lymphomatoid Papulosis Papular Urticaria Pityriasis Lichenoides
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| Drug Name | Isoniazid (Laniazid, Nydrazid) |
|---|---|
| Description | Best combination of effectiveness, low cost, and minor adverse effects. First-line drug unless resistance or another contraindication is known. Therapeutic regimens of <6 mo demonstrate an unacceptably high relapse rate. Coadministration of pyridoxine is recommended to minimize risk of peripheral neuropathy secondary to isoniazid therapy. Prophylactic doses of 6-50 mg of pyridoxine daily are recommended. Twice-weekly dosing not recommended in HIV patients with CD4 lymphocyte counts <100 cells/µL |
| Adult Dose | 5 mg/kg PO qd (usually 300 mg/d); 10 mg/kg PO qd or divided bid in patients with disseminated disease; not to exceed 300 mg/d Directly observed therapy: 15 mg/kg twice weekly; not to exceed 900 mg/d; twice-weekly dosing not recommended in HIV patients with CD4 lymphocyte counts <100 cells/µL |
| Pediatric Dose | 10-20 mg/kg PO qd; not to exceed 300 mg/d |
| Contraindications | Documented hypersensitivity; previous isoniazid-associated hepatic injury or other severe adverse reactions |
| Interactions | Higher incidence of isoniazid-related hepatitis can occur with daily alcohol consumption; aluminum salts may decrease serum levels (administer 1-2 h before taking aluminum salts); may increase effects of anticoagulants with coadministration; may inhibit metabolic clearance of benzodiazepines; carbamazepine toxicity or isoniazid hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations and liver function); coadministration with cycloserine may increase CNS adverse effects (eg, dizziness); acute behavioral and coordination changes may occur with coadministration of disulfiram; coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy; may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations during isoniazid therapy are recommended even when visual symptoms do not occur Adverse effects include anemia, seizure, systemic lupus erythematosus, thrombocytopenia, and hepatitis (severe and sometimes fatal); adverse effects following isoniazid therapy may include toxic encephalopathy, nystagmus, dizziness, and tinnitus |
| Drug Name | Rifampin (Rifadin, Rimactane) |
|---|---|
| Description | For use in combination with at least 1 other anti-TB drug. Inhibits DNA-dependent bacterial RNA polymerase but not mammalian RNA polymerase. Cross-resistance may occur. Treat for 6-9 mo or until 6 mo have elapsed from conversion to sputum culture negativity. |
| Adult Dose | 600 mg PO/IV qd |
| Pediatric Dose | 10-20 mg/kg PO/IV; not to exceed 600 mg/d |
| Contraindications | Documented hypersensitivity |
| Interactions | Induces microsomal enzymes (especially P450 CYP3A4-mediated metabolism), which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, digoxin, and other medications metabolized by this system; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue 1 or both agents if alterations in LFTs occur) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Obtain CBC counts and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur |
| Drug Name | Pyrazinamide |
|---|---|
| Description | Pyrazine analog of nicotinamide that may be bacteriostatic or bactericidal against M tuberculosis, depending on concentration of drug attained at site of infection; mechanism of action is unknown. Administer for initial 2 months of a 6-mo or longer treatment regimen for drug-susceptible patients. Treat drug-resistant patients with individualized regimens. |
| Adult Dose | 15-30 mg/kg PO qd; not to exceed 2 g/d Indirectly observed therapy: 50-70 mg/kg PO 2 times/wk, not to exceed 4 g/d; or 50-70 mg/kg 3 times/wk, not to exceed 3 g/d |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; severe hepatic damage; acute gout |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Use only in combination with other effective anti-TB agents; inhibits renal excretion of urates; may result in hyperuricemia (usually asymptomatic); perform baseline serum uric acid determinations; discontinue drug if signs of hyperuricemia with acute gouty arthritis; perform baseline LFTs (closely monitor in liver disease); discontinue if signs of hepatocellular damage appear; caution in history of diabetes mellitus; coadministration of ethionamide may potentiate hepatotoxicity |
| Drug Name | Ethambutol (Myambutol) |
|---|---|
| Description | Diffuses into actively growing mycobacterial cells, such as tubercle bacilli. Impairs cell metabolism by inhibiting synthesis of one or more metabolites, which, in turn, causes cell death. No cross-resistance demonstrated. Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with second-line drugs that have not been previously administered. Administer qd until permanent bacteriologic conversion and maximal clinical improvement is seen. Absorption is not significantly altered by food. |
| Adult Dose | No previous anti-TB therapy: 15 mg/kg (7 mg/lb) PO qd Previous anti-TB therapy: 25 mg/kg (11 mg/lb) PO qd |
| Pediatric Dose | <13 years: Not recommended >13 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; optic neuritis (unless clinically indicated) |
| Interactions | Aluminum salts may delay and reduce absorption (give several hours before or after ethambutol dose) |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Reduce dose in impaired renal function; may have reversible visual adverse effects if promptly discontinued |
| Media file 1: Bilaterally symmetric papulonecrotic lesions on the lower extremities. | |
 | View Full Size Image | Media type: Photo |
Papulonecrotic Tuberculids excerpt
Article Last Updated: Jan 26, 2007
