Mortality hazard and survival after tuberculosis treatment.

OBJECTIVES: We compared mortality among tuberculosis (TB) survivors and a similar population. METHODS: We used local health authority records from 3 US sites to identify 3853 persons who completed adequate treatment of TB and 7282 individuals diagnosed with latent TB infection 1993 to 2002. We then retrospectively observed mortality after 6 to 16 years of observation. We ascertained vital status as of December 31, 2008, using the Centers for Disease Control and Prevention's National Death Index. We analyzed mortality rates, hazards, and associations using Cox regression. RESULTS: We traced 11 135 individuals over 119 772 person-years of observation. We found more all-cause deaths (20.7% vs 3.1%) among posttreatment TB patients than among the comparison group, an adjusted average excess of 7.6 deaths per 1000 person-years (8.8 vs 1.2; P < .001). Mortality among posttreatment TB patients varied with observable factors such as race, site of disease, HIV status, and birth country. CONCLUSIONS: Fully treated TB is still associated with substantial mortality risk. Cure as currently understood may be insufficient protection against TB-associated mortality in the years after treatment, and TB prevention may be a valuable opportunity to modify this risk.

Three months of rifapentine and isoniazid for latent tuberculosis infection.

BACKGROUND: Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion. METHODS: We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%. RESULTS: In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P=0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001). CONCLUSIONS: The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.).

Bowel-Associated Dermatosis-Arthritis Syndrome: A Case Report.

Introduction: Gastric bypass surgery is an effective surgical intervention for morbid obesity. However, it is not without risk. Gastric bypass surgery may produce malabsorptive or surgical complications, which can result in nutritional deficiencies as well as syndromes related to bacterial overgrowth in the blind loops of the bowel. Case Presentation: Severe nutritional deficiencies may occur due to patient noncompliance with the prescribed regimen, or arise secondary to malabsorptive or mechanical surgical complications. We describe a case of a 37-year-old female who underwent gastric bypass surgery and experienced a recalcitrant eczematous eruption with sporadic subcutaneous, purulent nodules which completely resolved after the reversal of her bariatric procedure. Conclusion: Since 2001, the number of morbidly obese patients who have undergone bariatric surgery has been increasing. As a result, clinicians can expect to more frequently encounter complications that can result from these procedures.

Presentations of Cutaneous Disease in Various Skin Pigmentations: Acne Vulgaris - Comedonal Acne.

Description Acne vulgaris is a common inflammatory skin condition of the pilosebaceous unit in adolescents and young adults and is primarily characterized by the presence of open and closed comedones. In patients of various skin pigmentations, skin-colored comedones may be difficult to appreciate and lead to incorrect or delayed diagnosis of acne. To aid in the identification of acne vulgaris in patients of various skin pigmentations, we present comedonal acne in different skin types and commonly encountered differential diagnoses. With its significant volume and burden of disease, acne vulgaris should be correctly identified in various skin pigmentations by primary care clinicians for the initiation of appropriate management.

Complete Clearance of Pustular Psoriasis After A Single Dose of Risankizumab.

Introduction: Psoriasis is a chronic, multifactorial, inflammatory skin disease with several subtypes, including pustular psoriasis. Pustular psoriasis is characterized by pustules forming lakes of pus on the skin. Pro-inflammatory pathways, such as the interleukin (IL)-17/IL-23 axis, have been shown to play a significant role in the pathogenesis of psoriasis. Biologic therapies directed towards these pro-inflammatory pathways have effectively treated plaque psoriasis, but fewer treatments have shown similar efficacy for pustular psoriasis. Case Presentation: We present a 45-year-old Black female who presented to the dermatology clinic with generalized pustular psoriasis affecting approximately 70% of her body surface area. She also noted joint stiffness and pain that was worse after inactivity. Her disease did not respond to previous treatment, which was using adalimumab for 6 months. She also had no response to a 3-month course of apremilast.Two weeks after receiving her first dose of risankizumab, she had complete clearance of her pustular psoriasis, affecting 0% of her body surface area. She also noted significant improvement in her joint pain. Conclusions: There is little data regarding the efficacy of IL-23 inhibitors in treating generalized pustular psoriasis. To date, our case is the only reported instance in the literature showing rapid clearance of pustular psoriasis after 1 injection of risankizumab. This case illustrates that IL-23 inhibitors play an essential role in the rapid clearance of pustular psoriasis.

Resolved Peristomal Erosive Papulonodular Dermatitis Mimicking Nevoid Hyperkeratosis of the Nipple and Areola.

Introduction: Nevoid hyperkeratosis of the nipple and areola (NHKNA) is a rare cutaneous entity with a distinct clinical and histological presentation. The type II form of this condition can result from various dermatoses, such as irritant contact dermatitis. Erosive papulonodular dermatitis is a chronic irritant dermatitis that often occurs in areas of occlusion and maceration, such as peristomal skin. Pseudoverrucous papules and nodules are a variant of erosive papulonodular dermatitis and have a non-specific histologic pattern of reactive hyperplasia. Case Presentation: We present a case of a patient with resolved peristomal erosive papulonodular dermatitis who presented status-post ileostomy reversal with clinical and histologic findings classically seen in NHKNA. Conclusion: In type II NHKNA, treatment of the primary dermatosis typically leads to resolutions. In the case of our patient, removal of the offending agent via colostomy reversal and barrier protection led to the resolution of the lesions.

Treatment of high-grade anal intraepithelial neoplasia with infrared coagulation in a primary care population of HIV-infected men and women.

BACKGROUND: High-grade anal intraepithelial neoplasia, the putative anal carcinoma precursor, is more common in HIV-infected persons. The ideal treatment for these lesions has not been established. OBJECTIVE: The aim of this study was to evaluate the effectiveness of infrared coagulation treatment for high-grade anal intraepithelial neoplasia. DESIGN: This is a prospective cohort study. Patients with high-grade anal intraepithelial neoplasia either received infrared coagulation treatment or voluntarily did not receive treatment and were reevaluated at a subsequent time point. SETTING: This investigation was performed at a Ryan White-funded clinic located in the United States. PATIENTS: HIV-infected men and women with biopsy-confirmed high-grade anal intraepithelial neoplasia were included. MAIN OUTCOME MEASURES: The primary outcome measured was the histology collected by high-resolution anoscopy-directed biopsy. RESULTS: The study included 124 patients. Of 42 patients who either delayed treatment or were not treated, 37 (88%; 95% CI = 74%-96%) still had high-grade anal intraepithelial neoplasia on reevaluation and 2 (5%; 95%CI = 1%-16%) had squamous-cell carcinoma. Of 98 patients who received infrared coagulation treatment, 73 (74%; 95% CI = 65%-83%) patients had no evidence of high-grade anal intraepithelial neoplasia on their first posttreatment evaluation, and none had progressed to squamous-cell carcinoma (p < 0.0001 in comparison with untreated). Upon completing all initial and, if necessary, follow-up treatment, 85 (87%; 95% CI = 78%-93%) patients treated by infrared coagulation had no evidence of high-grade anal intraepithelial neoplasia and none had progressed to squamous-cell carcinoma. LIMITATIONS: The study population may not be representative of the general population, the study environment was uncontrolled, and patients were not randomly assigned to treatment. CONCLUSIONS: Infrared coagulation is an effective treatment for high-grade anal intraepithelial neoplasia.

Non-hispanic whites have higher risk for pulmonary impairment from pulmonary tuberculosis.

BACKGROUND: Disparities in outcomes associated with race and ethnicity are well documented for many diseases and patient populations. Tuberculosis (TB) disproportionately affects economically disadvantaged, racial and ethnic minority populations. Pulmonary impairment after tuberculosis (PIAT) contributes heavily to the societal burden of TB. Individual impacts associated with PIAT may vary by race/ethnicity or socioeconomic status. METHODS: We analyzed the pulmonary function of 320 prospectively identified patients with pulmonary tuberculosis who had completed at least 20 weeks standard anti-TB regimes by directly observed therapy. We compared frequency and severity of spirometry-defined PIAT in groups stratified by demographics, pulmonary risk factors, and race/ethnicity, and examined clinical correlates to pulmonary function deficits. RESULTS: Pulmonary impairment after tuberculosis was identified in 71% of non-Hispanic Whites, 58% of non-Hispanic Blacks, 49% of Asians and 32% of Hispanics (p < 0.001). Predictors for PIAT varied between race/ethnicity. PIAT was evenly distributed across all levels of socioeconomic status suggesting that PIAT and socioeconomic status are not related. PIAT and its severity were significantly associated with abnormal chest x-ray, p < 0.0001. There was no association between race/ethnicity and time to beginning TB treatment, p = 0.978. CONCLUSIONS: Despite controlling for cigarette smoking, socioeconomic status and time to beginning TB treatment, non-Hispanic White race/ethnicity remained an independent predictor for disproportionately frequent and severe pulmonary impairment after tuberculosis relative to other race/ethnic groups. Since race/ethnicity was self reported and that race is not a biological construct: these findings must be interpreted with caution. However, because race/ethnicity is a proxy for several other unmeasured host, pathogen or environment factors that may contribute to disparate health outcomes, these results are meant to suggest hypotheses for further research.

Delayed Diagnosis of Klippel-Trénaunay Syndrome in a 23-year-old African American Male.

Description Klippel-Trénaunay syndrome is a rare genetic disorder that typically presents as a triad of symptoms consisting of venous malformations (varicosities), capillary malformations (port-wine stain), and limb overgrowth. We followed a 23-year-old African American male with a past medical history of peripheral vascular disease, who was visiting the dermatology clinic for a persistent skin lesion on his thigh. During physical examinations, we noted a subtle port-wine stain on his right leg, right leg hypertrophy, and peripheral vascular disease. Skin findings were difficult to observe on his darker skin tone, Fitzpatrick skin type VI, which may have led to the delayed diagnosis of Klippel-Trénaunay syndrome. The lesion of concern was removed during a follow-up visit and was consistent with an angiokeratoma. Our patient had not suffered any serious complications from his new diagnosis of Klippel-Trénaunay syndrome; however, there was a concern for thrombotic events.

Presentations of Cutaneous Disease in Various Skin Pigmentations: An Introduction.

Description Dermatological disease has historically been dependent on photography as a primary modality for education. Previously, photographs used for medical education were representative of the regional patient populations at that time; however, they have not proportionally reflected the rapidly changing demographics in the United States. Education on the diagnosis of cutaneous disease has, therefore, primarily relied on photographs of lighter skin tones. There is a need for a better representation of darker skin tones in dermatologic medical education. This article introduces a clinical series that highlights dermatological diseases in various skin pigmentations, which are commonly seen in the primary care office. The goal is to improve the diagnostic accuracy of primary care clinicians and to compare how certain cutaneous diseases may vary in appearance depending on the individuals' Fitzpatrick skin type.

Acyclovir-Resistant Anogenital Herpes Simplex Virus in an HIV Patient With Pseudoepitheliomatous Hyperplasia Resembling Squamous Cell Carcinoma.

Background: Herpes simplex virus (HSV) is a common infection. However, it may present atypically when patients are immunocompromised, such as with slowly expanding, long-lasting ulcerative or hypertrophic lesions. The histopathologic finding of pseudoepitheliomatous hyperplasia (PEH) can occur in a variety of situations where there is chronic inflammation and can be seen in patients with chronic HSV. Atypical presentations of HSV, particularly hypertrophic lesions with histopathologic findings of PEH, can be misinterpreted as squamous cell carcinoma, create difficulty in diagnosis and hinder appropriate treatment. Case Description: We report a case of a 59-year-old female with a past medical history of human immunodeficiency virus (HIV), who presented at a dermatology clinic with multiple exophytic ulcerations of varying sizes in the perianal region. The patient was diagnosed with HSV and was started on valacyclovir. Over a several-year period, the patient had multiple recurrences of her HSV lesions with persistent vulvodynia despite prophylactic treatment with valacyclovir. Specimens were collected for culture and sensitivities, which revealed acyclovir resistance. The patient's lesions were biopsied due to concern for possible malignancy. Biopsies revealed prominent PEH. The patient had improvement of her HSV with saucerization, topical imiquimod, and increased doses of prophylactic valacyclovir. Conclusion: Atypical, chronic presentations of HSV are common in immunocompromised patients. Hypertrophic HSV is the least common clinical presentation and can be mistaken for squamous cell carcinoma, creating difficulty in diagnosis. Due to concerns for malignancy, our patient's lesions were biopsied, which revealed prominent PEH. While PEH is benign, it can be misdiagnosed as squamous cell carcinoma on histopathology, particularly when there is clinical suspicion for malignancy. In these cases, the clinician needs to alert the pathologist to the immunosuppressed status of the patient. Detailed evaluation for infectious causes, such as HSV, can avoid misinterpretation and potential surgical and oncological overtreatment.

Congenital Giant Juvenile Xanthogranuloma, Let It Be.

Description Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. JXGs are benign and have a self-limiting course generally lasting 6 months to 3 years, with some reported durations longer than 6 years. We present a rarer congenital giant variant, defined as lesions with a diameter larger than 2 cm. It is uncertain if the natural history of giant xanthogranulomas is similar to the usual JXG. We followed a 5-month-old patient with a 3.5 cm in diameter, histopathologically-confirmed, congenital, giant JXG located on the right side of her upper back. The patient was seen every 6 months for 2.5 years. At 1 year of age, the lesion had decreased in size, lightened in color, and was less firm. At 1.5 years old, the lesion had flattened. By 3 years old, the lesion had resolved but left a hyperpigmented patch with a scar at the punch biopsy site. Our case represents a congenital giant JXG that was biopsied to confirm the diagnosis and then monitored until resolution. This case supports the clinical course of giant JXG not being affected by the larger lesion size and that aggressive treatments or procedures are not warranted.

Pleomorphic Dermal Sarcoma: A Clinical and Histopathologic Emulator of Atypical Fibroxanthoma, but Different Biologic Behavior.

Description Pleomorphic dermal sarcoma (PDS) can clinically and histopathologically mimic atypical fibroxanthoma (AFX). However, it has a more aggressive clinical course with a higher recurrence rate and metastatic potential. This case presentation aims to report a rapidly-growing, exophytic, 4 cm tumor following a non-diagnostic shave biopsy 2 months prior and to highlight distinctive features between PDS and AFX needed to make the correct diagnosis. Like AFX, PDS occurs on the sun-damaged skin of the elderly, usually on the head and neck. Also, like AFX, PDS histopathologically consists of sheets or fascicles of epithelioid and/or spindle-shaped cells, often with multinucleation, pleomorphism, and numerous mitotic figures. Immunohistochemistry cannot distinguish PDS from AFX but is used to exclude other malignancies. PDS can be distinguished from AFX by size (PDS is usually >2.0 cm) and by the presence of more aggressive histopathologic features, such as subcutaneous involvement, perineural and/or lymphovascular invasion, and necrosis. PDS is a rare entity not well documented in the literature with confusing, misleading, and changing nomenclature. PDS is a diagnosis of exclusion made after complete excision of the tumor with the aid of histopathology and immunohistochemistry.

Linear Cutaneous Lupus Erythematosus Following Blaschko's Lines on the Scalp: Additional Cases and Review of the Literature.

Description Alopecia of the scalp has various causes and presentations. However, linear alopecia is unusual and lupus erythematosus presenting as linear alopecia is exceedingly rare. To date, there have been 16 documented cases of linear alopecia diagnosed as chronic cutaneous lupus erythematosus occurring in a linear configuration following Blaschko's lines. We report 2 additional cases and review the clinical and histologic features along with treatment. This Blaschkoid linear variant of cutaneous lupus erythematosus has distinct clinical and histologic characteristics that set it apart from other causes of alopecia and from classic forms of cutaneous lupus. These distinct features include a linear configuration, a younger age of presentation, a disproportionate number of Asians affected, and a paucity of cases with systemic involvement. Histologically, the lesions are characterized by prominent mucin in the dermis and subcutaneous tissues. Blaschkoid linear lupus of the scalp is sufficiently distinctive to suggest the diagnosis on histology alone, in the appropriate clinical context. The most common and successful treatments included systemic and/or combination treatment with oral hydroxychloroquine, oral steroids, and/or intralesional steroids.

Presentations of Cutaneous Disease in Various Skin Pigmentations: Inverse Psoriasis.

Description Inverse psoriasis is a clinical variant of psoriasis involving flexural or intertriginous areas of the body. Inverse psoriasis may be present in 3 to 36% of psoriasis patients. Lesions are clinically characterized as smooth, well-demarcated, erythematous plaques (raised, >1 cm) without the typical silvery scales of classic psoriasis. Differential diagnosis includes tinea infection, candidiasis, seborrheic dermatitis, or bacterial streptococcal infection. The clinical images in this review focus on identifying inverse psoriasis along the full spectrum of skin tones.

Presentations of Cutaneous Disease in Various Skin Pigmentations: Cutaneous Abscesses.

Description Cutaneous abscesses are collections of pus resulting from skin and soft tissue bacterial infections. They clinically exhibit the four cardinal inflammatory signs of pain, warmth, swelling, and erythema. In patients with darkly pigmented skin, classically-associated erythema may be challenging to appreciate and can lead to missed or delayed diagnosis. We compare abscess presentations in different skin types. Recognition of varying presentations of cutaneous abscesses in diverse skin colors will help clinicians utilize additional clues to identify and diagnose this entity correctly.

Presentations of Cutaneous Disease in Various Skin Pigmentations: Plaque Psoriasis.

Description Recent studies estimate that more than 8 million Americans have psoriasis. The prevalence of psoriasis in African Americans is 1.5% compared to 3.6% of Caucasians. Psoriasis is likely to be underdiagnosed among African Americans and other individuals with darker pigmented skin due to variations in clinical presentation in addition to disease distribution and severity. We present images of psoriasis vulgaris in a variety of Fitzpatrick skin types. Differences in the biology of skin pigmentation may explain the clinical masking of erythema in darker-skinned individuals. Recognition of this important difference will help clinicians utilize additional clues to identify and diagnose this entity correctly.

Prevalence of anal intraepithelial neoplasia defined by anal cytology screening and high-resolution anoscopy in a primary care population of HIV-infected men and women.

BACKGROUND: Prevalence of high-grade anal intraepithelial neoplasia, the human papillomavirus-associated putative anal cancer precursor, is high in HIV-infected men who have sex with men, but less is known about its prevalence in other HIV-infected subgroups. Similarly, the prevalence of abnormal cytology, used as a screen, is not well-defined in these subgroups. OBJECTIVE: This study aimed to estimate the prevalence of abnormal cytology and anal intraepithelial neoplasia in a primary care HIV-infected population. DESIGN: This investigation was designed as a cross-sectional study. SETTING: This study took place at a Ryan White-funded clinic. PATIENTS: Included in the study were all (n = 779) HIV-infected patients receiving primary care services between March 2006 and March 2008. MAIN OUTCOME MEASURES: The main outcome measures were anal cytology and high-resolution anoscopy results. RESULTS: The prevalence of abnormal cytology was 43%: 62% in men who reported receptive anal intercourse, 39% in women who reported receptive anal intercourse, and 25% in all others (P trend <.0001). High-grade anal intraepithelial neoplasia prevalence was 27%: 44% in men who reported receptive anal intercourse, 26% in women who reported receptive anal intercourse, and 10% in all others (P trend <.0001). Two patients had squamous-cell cancer. Independent predictors of dysplasia were CD4 at screening, receptive anal intercourse, sexual orientation, and history of human papillomavirus disease. Anal cytology and histology findings were not well correlated. LIMITATIONS: The study population may not be representative of the general HIV-infected population, there were differences between screened and unscreened patients and between patients with abnormal cytology who had high-resolution anoscopy and those who did not, only patients with abnormal cytology had high-resolution anoscopy, and there were possible misclassification errors and uncontrolled possible confounders. CONCLUSIONS: High-grade anal intraepithelial neoplasia is relatively common in HIV-infected patients regardless of sexual practice. Although risk increases with receptive anal intercourse, patient-provided information on this sexual practice should not be used as a determining factor for screening. Strategies to prevent anal cancer are necessary for all HIV-infected patients.

ESAT-6 inhibits production of IFN-gamma by Mycobacterium tuberculosis-responsive human T cells.

The Mycobacterium tuberculosis early secreted Ag of 6 kDa (ESAT-6) is a potent Ag for human T cells and is a putative vaccine candidate. However, ESAT-6 also contributes to virulence in animal models, mediates cellular cytolysis, and inhibits IL-12 production by mononuclear phagocytes. We evaluated the effects of ESAT-6 and its molecular chaperone, culture filtrate protein of 10 kDa (CFP10), on the capacity of human T cells to produce IFN-gamma and proliferate in response to TCR activation. Recombinant ESAT-6, but not CFP10, markedly inhibited IFN-gamma production by T cells stimulated with M. tuberculosis or with the combination of anti-CD3 and anti-CD28, in a dose-dependent manner. ESAT-6 also inhibited T cell production of IL-17 and TNF-alpha but not IL-2. Preincubation of ESAT-6 with CFP10 under conditions that favor dimer formation did not affect inhibition of IFN-gamma. ESAT-6 decreased IFN-gamma transcription and reduced expression of the transcription factors, ATF-2 and c-Jun, which normally bind to the IFN-gamma proximal promoter and stimulate mRNA expression. ESAT-6 inhibited T cell IFN-gamma secretion through mechanisms that did not involve cellular cytotoxicity or apoptosis. ESAT-6, but not CFP10, bound to T cells and inhibited expression of early activation markers without reducing activation of ZAP70. We conclude that ESAT-6 directly inhibits human T cell responses to mycobacterial Ags by affecting TCR signaling pathways downstream of ZAP70.

Does directly observed therapy (DOT) reduce drug resistant tuberculosis?

BACKGROUND: Directly observed therapy (DOT) is a widely recommended and promoted strategy to manage tuberculosis (TB), however, there is still disagreement about the role of DOT in TB control and the impact it has on reducing the acquisition and transmission of drug resistant TB. This study compares the portion of drug resistant genotype clusters, representing recent transmission, within and between communities implementing programs differing only in their directly observed therapy (DOT) practices. METHODS: Genotype clusters were defined as 2 or more patient members with matching IS6110 restriction fragment length polymorphism (RFLP) and spoligotype patterns from all culture-positive tuberculosis cases diagnosed between January 1, 1995 and December 31, 2001. Logistic regression was used to compute maximum-likelihood estimates of odds ratios (ORs) and 95% confidence intervals (CIs) comparing cluster members with and without drug resistant isolates. In the universal DOT county, all patients received doses under direct observation of health department staff; whereas in selective DOT county, the majority of received patients doses under direct observation of health department staff, while some were able to self-administer doses. RESULTS: Isolates from 1,706 persons collected during 1,721 episodes of tuberculosis were genotyped. Cluster members from the selective DOT county were more than twice as likely than cluster members from the universal DOT county to have at least one isolate resistant to isoniazid, rifampin, and/or ethambutol (OR = 2.3, 95% CI: 1.7, 3.1). Selective DOT county isolates were nearly 5 times more likely than universal DOT county isolates to belong to clusters with at least 2 resistant isolates having identical resistance patterns (OR = 4.7, 95% CI: 2.9, 7.6). CONCLUSIONS: Universal DOT for tuberculosis is associated with a decrease in the acquisition and transmission of resistant tuberculosis.