Introduction Psoriasis is a chronic, multifactorial, inflammatory skin disease with several subty... more 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.
Pleomorphic dermal sarcoma (PDS) can clinically and histopathologically mimic atypical fibroxanth... more 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.
Background Herpes simplex virus (HSV) is a common infection. However, it may present atypically w... more 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.
Description Klippel-Trénaunay syndrome is a rare genetic disorder that typically presents as a tr... more Description Klippel-Trénaunay syndrome is a rare genetic disorder that typically presents as a triad of symptoms consisting of venous malformations (varicosities), capillary malformations (portwine 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.
Description Cutaneous abscesses are collections of pus resulting from skin and soft tissue bacter... more 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.
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2005
Urban county health department in Tarrant County, Texas, USA. To determine the yield of associate... more Urban county health department in Tarrant County, Texas, USA. To determine the yield of associate investigations in non-bacille Calmette-Guerin (BCG) immunized children with positive tuberculin skin tests (TSTs). We compared the results of associate investigations of the contacts of 38 TST-positive, non-BCG-immunized pre-school children with the results of contact investigations of 290 culture-confirmed persons with tuberculosis (TB). Associate investigations were more likely than contact investigations to identify persons with culture-confirmed TB and positive TSTs. Contacts identified through associate investigation of non-BCG-immunized pre-school children were 9.4 (95%CI 4.2-22.5) times more likely to have culture-confirmed TB and 2.3 (95%CI 2.0-2.7) times more likely to have positive TSTs than contacts of persons with culture-confirmed TB. While conducting associate investigations is labor intensive, these data indicate that associate investigation of pre-school non-BCG-immunize...
Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. JXGs are beni... more 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.
American Journal of Respiratory and Critical Care Medicine, Jun 1, 2004
The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during once-weekly con... more The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during once-weekly continuation phase therapy in 35 patients with tuberculosis. Mean area under the plasma concentration-time curve (AUC 0-∞) increased significantly with dose (rifapentine AUC 0-∞ : 296, 410, and 477 g • hour/ml at 600, 900, and 1,200 mg, respectively; p ϭ 0.02 by linear regression). In multivariate stepwise regression analyses, AUC 0-∞ values for rifapentine and the active 25-desacetyl metabolite were associated with drug dose and plasma albumin concentration, and were lower among men and among white individuals. Fifty-four percent of patients had total (free and protein-bound) plasma concentrations of rifapentine and of desacetyl rifapentine detected for more than 36 hours after clearance of concurrently administered isoniazid. Serious adverse effects of therapy in these study patients were infrequent (1 of 35 cases; 3%) and not linked with higher rifapentine AUC 0-∞ or peak concentration. The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis.
American Journal of Respiratory and Critical Care Medicine, Nov 1, 2005
Rationale: Diagnosis of latent tuberculosis infection (LTBI) is currently based on the tuberculin... more Rationale: Diagnosis of latent tuberculosis infection (LTBI) is currently based on the tuberculin skin test. The enzyme-linked immunospot assay (ELISPOT) is a new blood test to diagnose LTBI. Objective: To compare the ELISPOT and the tuberculin skin test for detecting LTBI in contacts of patients with tuberculosis. Methods: Prospective study of 413 contacts of patients with tuberculosis. Measurements and Main Results: Because there is no gold standard for LTBI, the sensitivity and specificity of the ELISPOT and tuberculin skin test cannot be directly measured. For each contact, we therefore estimated the likelihood of having LTBI by calculating a contact score that quantified exposure to and infectiousness of the index case. We analyzed the relationship of contact score to ELISPOT and tuberculin skin test results. The likelihood of a positive ELISPOT (p ϭ 0.0005) and a tuberculin skin test (p ϭ 0.01) increased significantly with rising contact scores. The contact score was more strongly related to the ELISPOT than to the tuberculin skin test results, although this difference was not statistically significant. Among U.S.-born persons and those who were not vaccinated with bacille Calmette-Guérin, approximately 30% had positive ELISPOT or tuberculin skin test results. Foreign-born, bacille Calmette-Guérin-vaccinated persons were significantly more likely to have a positive tuberculin skin test than a positive ELISPOT result (p Ͻ 0.0001). Conclusions: Compared with the tuberculin skin test, the ELISPOT appears to be at least as sensitive for diagnosis of LTBI in contacts of patients with tuberculosis.
Evaluation improves efficiency and effectiveness. Current U.S. tuberculosis (TB) control policies... more Evaluation improves efficiency and effectiveness. Current U.S. tuberculosis (TB) control policies emphasize the treatment of latent TB infection (LTBI). However, this policy, if not targeted, may be inefficient. We determined the efficiency of a state-law mandated TB screening program and a non statelaw mandated one in terms of cost, morbidity, treatment, and disease averted. METHODS: We evaluated two publicly funded metropolitan TB prevention and control programs through retrospective analyses and modeling. Main outcomes measured were TB incidence and prevalence, TB cases averted, and cost. RESULTS: A non state-law mandated TB program for homeless persons in Tarrant County screened 4.5 persons to identify one with LTBI and 82 persons to identify one with TB. A state-law mandated TB program for jail inmates screened 109 persons to identify one with LTBI and 3274 persons to identify one with TB. The number of patients with LTBI treated to prevent one TB case was 12.1 and 15.3 for the homeless and jail inmate TB programs, respectively. Treatment of LTBI by the homeless and jail inmate TB screening programs will avert 11.9 and 7.9 TB cases at a cost of $14,350 and $34,761 per TB case, respectively. CONCLUSIONS: Mandated TB screening programs should be risk-based, not population-based. Non mandated targeted testing for TB in congregate settings for the homeless was more efficient than statelaw mandated targeted testing for TB among jailed inmates.
International Journal of Health Geographics, Oct 13, 2004
Background: Currently in the U.S. it is recommended that tuberculosis screening and treatment pro... more Background: Currently in the U.S. it is recommended that tuberculosis screening and treatment programs be targeted at high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. In this study we seek to identify geographical areas where ongoing tuberculosis transmission is occurring by linking Geographic Information Systems (GIS) technology with molecular surveillance. Methods: This cross-sectional analysis was performed on data collected on persons newly diagnosed with culture positive tuberculosis at the Tarrant County Health Department (TCHD) between January 1, 1993 and December 31, 2000. Clinical isolates were molecularly characterized using IS6110-based RFLP analysis and spoligotyping methods to identify patients infected with the same strain. Residential addresses at the time of diagnosis of tuberculosis were geocoded and mapped according to strain characterization. Generalized estimating equations (GEE) analysis models were used to identify risk factors involved in clustering. Results: Evaluation of the spatial distribution of cases within zip-code boundaries identified distinct areas of geographical distribution of same strain disease. We identified these geographical areas as having increased likelihood of ongoing transmission. Based on this evidence we plan to perform geographically based screening and treatment programs. Conclusion: Using GIS analysis combined with molecular epidemiological surveillance may be an effective method for identifying instances of local transmission. These methods can be used to enhance targeted screening and control efforts, with the goal of interruption of disease transmission and ultimately incidence reduction.
American Journal of Respiratory and Critical Care Medicine, Mar 1, 2008
Dr. Kuschner points out that the calibration factor we used in our article investigating the rela... more Dr. Kuschner points out that the calibration factor we used in our article investigating the relationship of health status to indoor fine particle levels (1) may have been appropriate for the studies we referenced, but may not have been correct for our sources. We have realized that the reference numbers are incorrect in the Methods of the main paper, and this section should refer to the references cited herein (2, 3), which are those in the online Methods supplement. This may in part answer Dr. Kuschner's concern. More generally, use of a different calibration factor would not influence the relationship between increasing PM 2.5 concentration and decreasing health status. The studies we quote for calibration were undertaken in indoor environments, and we think it is reasonable to believe that sources of particles are similar to those present in the homes we monitored. Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
There is increasing controversy about the appropriate role of the local institutional review boar... more There is increasing controversy about the appropriate role of the local institutional review board in the review of multicenter clinical studies. We evaluated the effects of the local review process at 25 study sites on the consent forms from two studies of the Tuberculosis Trials Consortium, a multicenter trials group. Two independent reviewers classified all changes made in the centrally approved consent forms; a third reviewer evaluated those changes if the two initial reviewers disagreed. The median time to initial local approval was 104.5 days (range 31-346). There were no changes in the study protocols as a result of local review. Consent forms became longer and less readable after local review, with a mean increase in grade level of 0.9 (Ϯ0.9) reading grade levels (p Ͻ 0.001). A median of 46.5 changes (range 3-160) were made in the centrally approved forms. Most changes (85.2%) involved altering wording without affecting meaning. Errors were commonly introduced (11.2% of changes), and 33 of 50 (66%) locally approved consent forms contained at least one error in protocol presentation or a required consent form element. Local approval of two multicenter clinical trials was time-consuming and resulted in many changes in centrally approved consent forms. These changes frequently decreased readability and introduced errors.
American Journal of Respiratory and Critical Care Medicine, May 15, 2003
To understand why once-weekly isoniazid/rifapentine therapy for than rifampin (14-15 hours versus... more To understand why once-weekly isoniazid/rifapentine therapy for than rifampin (14-15 hours versus 2-5 hours, respectively) tuberculosis was less effective than twice-weekly isoniazid/rifampin, was undertaken with the hope that it would allow highly we studied human immunodeficiency virus-seronegative patients active once-weekly therapy. However, in three large randomwith either failure (n ϭ 4), relapse (n ϭ 35), or cure (n ϭ 94), reized trials (1-3), once-weekly isoniazid/rifapentine was less cruited from a comparative treatment trial. In multivariate analyses effective than twice-or thrice-weekly isoniazid/rifampin in that were adjusted for severity of disease, low plasma concentrathe last 4 months of treatment of active tuberculosis. tions of isoniazid were associated with failure/relapse with once-Two problems were identified in the randomized trials weekly isoniazid/rifapentine (median isoniazid area under the conof once-weekly isoniazid/rifapentine: a higher rate of drugcentration-time curve for 12 hours after the dose [AUC 0-12 ] was 36 susceptible relapse among human immunodeficiency virus g • hour/ml in failure/relapse versus 56 g • hour/ml in control (HIV)-negative patients and a substantial incidence of accases p ϭ 0.005), but not with twice-weekly isoniazid/rifampin. quired rifamycin-monoresistance among the small number Furthermore, two patients who relapsed with Mycobacterium tuberof HIV-positive patients treated with this regimen (4). Two culosis monoresistant to rifamycin had very low concentrations of theories have been proposed to explain these findings. Mitisoniazid. Finally, isoniazid acetylator status determined by N-acetylchison suggested that the dose of rifapentine used in all three transferase type 2 genotype was associated with outcome with trials (600-750 mg) may have been inadequate, analogous once-weekly isoniazid/rifapentine (p ϭ 0.03) but not twice-weekly to the decreased activity of the 450-mg dose of rifampin, isoniazid/rifampin. No rifamycin pharmacokinetic parameter was compared with the 600-mg dose, in early clinical trials of that consistently and significantly associated with outcome (p Ͼ 0.10). Because low isoniazid concentrations were associated with failure/ rifamycin (5). However, the occurrence of acquired rifamyrelapse, a drug with consistently greater area under the concentracin-monoresistance suggests that the activity of the compantion-time curve than isoniazid may be needed to achieve highly ion drug, in this case isoniazid, was inadequate to prevent the active once-weekly therapy with rifapentine. selection of rifamycin-resistant Mycobacterium tuberculosis. These two theories lead to substantially different interven
American Journal of Respiratory and Critical Care Medicine, Sep 15, 2001
The epidemiology of tuberculosis is changing in the United States as a result of immigration, yet... more The epidemiology of tuberculosis is changing in the United States as a result of immigration, yet the extent to which different classes of immigrants contribute to overall morbidity is unknown. Tuberculosis in nonimmigrant visitors is of particular interest as they are currently exempt from screening requirements. We conducted a prospective survey of all culture-positive tuberculosis patients in Tarrant County, Texas from 1/98 to 12/00. Immigration status of foreign-born patients was classified as permanent residents, undocumented, or nonimmigrant visitors. Of 274 eligible participants, 114 (42%) were foreign-born; of these, 67 (59%) were permanent residents, 28 (25%) were undocumented, and 19 (17%) were nonimmigrant visitors. Among the foreign-born, we observed significant differences by immigration status in multidrug resistance (p ϭ 0.02), human immunodeficiency virus (HIV) infection (p ϭ 0.0007), and hospitalization (p ϭ 0.03 for ever/never, 0.01 for duration). Compared with other immigrants, more nonimmigrant visitors were multi-drug-resistant (16 % versus 11% of undocumented residents and 1% of permanent residents), were HIV-positive (32% versus 0% of undocumented and 5% of permanent residents), were hospitalized (47% versus 36% of undocumented and 19% of permanent residents), and had lengthy hospitalizations (median [midspread] days ϭ 87 [25 to 153] versus 8.5 [4 to 28] for undocumented and 10 [7 to 24 d] for permanent residents). We found nonimmigrant visitors to be an important source of tuberculosis morbidity in Tarrant County. Further studies in other regions of the U.S. are needed to determine if screening and treatment recommendations of persons who spend extended periods in the U.S. should be raised to the standards set for permanent residents.
Poor adherence to tuberculosis (TB) treatment hinders the individual's recovery and threatens pub... more Poor adherence to tuberculosis (TB) treatment hinders the individual's recovery and threatens public health. Currently, directly observed therapy (DOT) is the standard of care; however, high sustaining costs limit its availability, creating a need for more practical adherence confirmation methods. Techniques such as video monitoring and devices to time-register the opening of pill bottles are unable to confirm actual medication ingestions. A novel approach developed by Proteus Digital Health, Inc. consists of an ingestible sensor and an on-body wearable sensor; together, they electronically confirm unique ingestions and record the date/time of the ingestion. A feasibility study using an early prototype was conducted in active TB patients to determine the system's accuracy and safety in confirming co-ingestion of TB medications with sensors. Thirty patients completed 10 DOT visits and 1,080 co-ingestion events; the system showed 95. 0% (95% CI 93. 5-96. 2%) positive detection accuracy, defined as the number of detected sensors divided by the number of transmission capable sensors administered. The specificity was 99. 7% [95% CI 99. 2-99. 9%] based on three false signals recorded by receivers. The system's identification accuracy, defined as the number of correctly identified ingestible sensors divided by the number of sensors detected, was 100%. Of 11 adverse events, four were deemed related or possibly related to the device; three mild skin rashes and one complaint of nausea. The system's positive detection accuracy was not affected by the subjects' Body Mass Index (p = 0. 7309). Study results suggest the system is capable of correctly identifying ingestible sensors with high accuracy, poses a low risk to users, and may have high patient acceptance. The system has the potential to confirm medication specific treatment compliance on a dose-by-dose basis. When coupled with mobile technology, the system could allow wirelessly observed therapy (WOT) for monitoring TB treatment as a replacement for DOT.
Chronic cutaneous lupus erythematosus in a linear configuration is rare, particularly in children... more Chronic cutaneous lupus erythematosus in a linear configuration is rare, particularly in children, demonstrating similar incidence in both genders, no photo-sensitivity and lower probability of progression to systemic disease. We describe the case of a 9-year-old girl who presented erythematous papules with central atrophy on the upper and lower right limbs, asymptomatic and following the lines of Blaschko, since age four. Histological examination showed atrophy of the epidermis with aggression from epidermal-dermal interface and periadnexal and perivascular lymphocytic inflammatory infiltrate. Laboratory tests showed ANA in a titer of 1:320, in a dense and fine speckled pattern. Due to the rarity of presentation and location of the disease, this case is reported here.
Introduction Psoriasis is a chronic, multifactorial, inflammatory skin disease with several subty... more 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.
Pleomorphic dermal sarcoma (PDS) can clinically and histopathologically mimic atypical fibroxanth... more 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.
Background Herpes simplex virus (HSV) is a common infection. However, it may present atypically w... more 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.
Description Klippel-Trénaunay syndrome is a rare genetic disorder that typically presents as a tr... more Description Klippel-Trénaunay syndrome is a rare genetic disorder that typically presents as a triad of symptoms consisting of venous malformations (varicosities), capillary malformations (portwine 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.
Description Cutaneous abscesses are collections of pus resulting from skin and soft tissue bacter... more 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.
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2005
Urban county health department in Tarrant County, Texas, USA. To determine the yield of associate... more Urban county health department in Tarrant County, Texas, USA. To determine the yield of associate investigations in non-bacille Calmette-Guerin (BCG) immunized children with positive tuberculin skin tests (TSTs). We compared the results of associate investigations of the contacts of 38 TST-positive, non-BCG-immunized pre-school children with the results of contact investigations of 290 culture-confirmed persons with tuberculosis (TB). Associate investigations were more likely than contact investigations to identify persons with culture-confirmed TB and positive TSTs. Contacts identified through associate investigation of non-BCG-immunized pre-school children were 9.4 (95%CI 4.2-22.5) times more likely to have culture-confirmed TB and 2.3 (95%CI 2.0-2.7) times more likely to have positive TSTs than contacts of persons with culture-confirmed TB. While conducting associate investigations is labor intensive, these data indicate that associate investigation of pre-school non-BCG-immunize...
Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. JXGs are beni... more 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.
American Journal of Respiratory and Critical Care Medicine, Jun 1, 2004
The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during once-weekly con... more The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during once-weekly continuation phase therapy in 35 patients with tuberculosis. Mean area under the plasma concentration-time curve (AUC 0-∞) increased significantly with dose (rifapentine AUC 0-∞ : 296, 410, and 477 g • hour/ml at 600, 900, and 1,200 mg, respectively; p ϭ 0.02 by linear regression). In multivariate stepwise regression analyses, AUC 0-∞ values for rifapentine and the active 25-desacetyl metabolite were associated with drug dose and plasma albumin concentration, and were lower among men and among white individuals. Fifty-four percent of patients had total (free and protein-bound) plasma concentrations of rifapentine and of desacetyl rifapentine detected for more than 36 hours after clearance of concurrently administered isoniazid. Serious adverse effects of therapy in these study patients were infrequent (1 of 35 cases; 3%) and not linked with higher rifapentine AUC 0-∞ or peak concentration. The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis.
American Journal of Respiratory and Critical Care Medicine, Nov 1, 2005
Rationale: Diagnosis of latent tuberculosis infection (LTBI) is currently based on the tuberculin... more Rationale: Diagnosis of latent tuberculosis infection (LTBI) is currently based on the tuberculin skin test. The enzyme-linked immunospot assay (ELISPOT) is a new blood test to diagnose LTBI. Objective: To compare the ELISPOT and the tuberculin skin test for detecting LTBI in contacts of patients with tuberculosis. Methods: Prospective study of 413 contacts of patients with tuberculosis. Measurements and Main Results: Because there is no gold standard for LTBI, the sensitivity and specificity of the ELISPOT and tuberculin skin test cannot be directly measured. For each contact, we therefore estimated the likelihood of having LTBI by calculating a contact score that quantified exposure to and infectiousness of the index case. We analyzed the relationship of contact score to ELISPOT and tuberculin skin test results. The likelihood of a positive ELISPOT (p ϭ 0.0005) and a tuberculin skin test (p ϭ 0.01) increased significantly with rising contact scores. The contact score was more strongly related to the ELISPOT than to the tuberculin skin test results, although this difference was not statistically significant. Among U.S.-born persons and those who were not vaccinated with bacille Calmette-Guérin, approximately 30% had positive ELISPOT or tuberculin skin test results. Foreign-born, bacille Calmette-Guérin-vaccinated persons were significantly more likely to have a positive tuberculin skin test than a positive ELISPOT result (p Ͻ 0.0001). Conclusions: Compared with the tuberculin skin test, the ELISPOT appears to be at least as sensitive for diagnosis of LTBI in contacts of patients with tuberculosis.
Evaluation improves efficiency and effectiveness. Current U.S. tuberculosis (TB) control policies... more Evaluation improves efficiency and effectiveness. Current U.S. tuberculosis (TB) control policies emphasize the treatment of latent TB infection (LTBI). However, this policy, if not targeted, may be inefficient. We determined the efficiency of a state-law mandated TB screening program and a non statelaw mandated one in terms of cost, morbidity, treatment, and disease averted. METHODS: We evaluated two publicly funded metropolitan TB prevention and control programs through retrospective analyses and modeling. Main outcomes measured were TB incidence and prevalence, TB cases averted, and cost. RESULTS: A non state-law mandated TB program for homeless persons in Tarrant County screened 4.5 persons to identify one with LTBI and 82 persons to identify one with TB. A state-law mandated TB program for jail inmates screened 109 persons to identify one with LTBI and 3274 persons to identify one with TB. The number of patients with LTBI treated to prevent one TB case was 12.1 and 15.3 for the homeless and jail inmate TB programs, respectively. Treatment of LTBI by the homeless and jail inmate TB screening programs will avert 11.9 and 7.9 TB cases at a cost of $14,350 and $34,761 per TB case, respectively. CONCLUSIONS: Mandated TB screening programs should be risk-based, not population-based. Non mandated targeted testing for TB in congregate settings for the homeless was more efficient than statelaw mandated targeted testing for TB among jailed inmates.
International Journal of Health Geographics, Oct 13, 2004
Background: Currently in the U.S. it is recommended that tuberculosis screening and treatment pro... more Background: Currently in the U.S. it is recommended that tuberculosis screening and treatment programs be targeted at high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. In this study we seek to identify geographical areas where ongoing tuberculosis transmission is occurring by linking Geographic Information Systems (GIS) technology with molecular surveillance. Methods: This cross-sectional analysis was performed on data collected on persons newly diagnosed with culture positive tuberculosis at the Tarrant County Health Department (TCHD) between January 1, 1993 and December 31, 2000. Clinical isolates were molecularly characterized using IS6110-based RFLP analysis and spoligotyping methods to identify patients infected with the same strain. Residential addresses at the time of diagnosis of tuberculosis were geocoded and mapped according to strain characterization. Generalized estimating equations (GEE) analysis models were used to identify risk factors involved in clustering. Results: Evaluation of the spatial distribution of cases within zip-code boundaries identified distinct areas of geographical distribution of same strain disease. We identified these geographical areas as having increased likelihood of ongoing transmission. Based on this evidence we plan to perform geographically based screening and treatment programs. Conclusion: Using GIS analysis combined with molecular epidemiological surveillance may be an effective method for identifying instances of local transmission. These methods can be used to enhance targeted screening and control efforts, with the goal of interruption of disease transmission and ultimately incidence reduction.
American Journal of Respiratory and Critical Care Medicine, Mar 1, 2008
Dr. Kuschner points out that the calibration factor we used in our article investigating the rela... more Dr. Kuschner points out that the calibration factor we used in our article investigating the relationship of health status to indoor fine particle levels (1) may have been appropriate for the studies we referenced, but may not have been correct for our sources. We have realized that the reference numbers are incorrect in the Methods of the main paper, and this section should refer to the references cited herein (2, 3), which are those in the online Methods supplement. This may in part answer Dr. Kuschner's concern. More generally, use of a different calibration factor would not influence the relationship between increasing PM 2.5 concentration and decreasing health status. The studies we quote for calibration were undertaken in indoor environments, and we think it is reasonable to believe that sources of particles are similar to those present in the homes we monitored. Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
There is increasing controversy about the appropriate role of the local institutional review boar... more There is increasing controversy about the appropriate role of the local institutional review board in the review of multicenter clinical studies. We evaluated the effects of the local review process at 25 study sites on the consent forms from two studies of the Tuberculosis Trials Consortium, a multicenter trials group. Two independent reviewers classified all changes made in the centrally approved consent forms; a third reviewer evaluated those changes if the two initial reviewers disagreed. The median time to initial local approval was 104.5 days (range 31-346). There were no changes in the study protocols as a result of local review. Consent forms became longer and less readable after local review, with a mean increase in grade level of 0.9 (Ϯ0.9) reading grade levels (p Ͻ 0.001). A median of 46.5 changes (range 3-160) were made in the centrally approved forms. Most changes (85.2%) involved altering wording without affecting meaning. Errors were commonly introduced (11.2% of changes), and 33 of 50 (66%) locally approved consent forms contained at least one error in protocol presentation or a required consent form element. Local approval of two multicenter clinical trials was time-consuming and resulted in many changes in centrally approved consent forms. These changes frequently decreased readability and introduced errors.
American Journal of Respiratory and Critical Care Medicine, May 15, 2003
To understand why once-weekly isoniazid/rifapentine therapy for than rifampin (14-15 hours versus... more To understand why once-weekly isoniazid/rifapentine therapy for than rifampin (14-15 hours versus 2-5 hours, respectively) tuberculosis was less effective than twice-weekly isoniazid/rifampin, was undertaken with the hope that it would allow highly we studied human immunodeficiency virus-seronegative patients active once-weekly therapy. However, in three large randomwith either failure (n ϭ 4), relapse (n ϭ 35), or cure (n ϭ 94), reized trials (1-3), once-weekly isoniazid/rifapentine was less cruited from a comparative treatment trial. In multivariate analyses effective than twice-or thrice-weekly isoniazid/rifampin in that were adjusted for severity of disease, low plasma concentrathe last 4 months of treatment of active tuberculosis. tions of isoniazid were associated with failure/relapse with once-Two problems were identified in the randomized trials weekly isoniazid/rifapentine (median isoniazid area under the conof once-weekly isoniazid/rifapentine: a higher rate of drugcentration-time curve for 12 hours after the dose [AUC 0-12 ] was 36 susceptible relapse among human immunodeficiency virus g • hour/ml in failure/relapse versus 56 g • hour/ml in control (HIV)-negative patients and a substantial incidence of accases p ϭ 0.005), but not with twice-weekly isoniazid/rifampin. quired rifamycin-monoresistance among the small number Furthermore, two patients who relapsed with Mycobacterium tuberof HIV-positive patients treated with this regimen (4). Two culosis monoresistant to rifamycin had very low concentrations of theories have been proposed to explain these findings. Mitisoniazid. Finally, isoniazid acetylator status determined by N-acetylchison suggested that the dose of rifapentine used in all three transferase type 2 genotype was associated with outcome with trials (600-750 mg) may have been inadequate, analogous once-weekly isoniazid/rifapentine (p ϭ 0.03) but not twice-weekly to the decreased activity of the 450-mg dose of rifampin, isoniazid/rifampin. No rifamycin pharmacokinetic parameter was compared with the 600-mg dose, in early clinical trials of that consistently and significantly associated with outcome (p Ͼ 0.10). Because low isoniazid concentrations were associated with failure/ rifamycin (5). However, the occurrence of acquired rifamyrelapse, a drug with consistently greater area under the concentracin-monoresistance suggests that the activity of the compantion-time curve than isoniazid may be needed to achieve highly ion drug, in this case isoniazid, was inadequate to prevent the active once-weekly therapy with rifapentine. selection of rifamycin-resistant Mycobacterium tuberculosis. These two theories lead to substantially different interven
American Journal of Respiratory and Critical Care Medicine, Sep 15, 2001
The epidemiology of tuberculosis is changing in the United States as a result of immigration, yet... more The epidemiology of tuberculosis is changing in the United States as a result of immigration, yet the extent to which different classes of immigrants contribute to overall morbidity is unknown. Tuberculosis in nonimmigrant visitors is of particular interest as they are currently exempt from screening requirements. We conducted a prospective survey of all culture-positive tuberculosis patients in Tarrant County, Texas from 1/98 to 12/00. Immigration status of foreign-born patients was classified as permanent residents, undocumented, or nonimmigrant visitors. Of 274 eligible participants, 114 (42%) were foreign-born; of these, 67 (59%) were permanent residents, 28 (25%) were undocumented, and 19 (17%) were nonimmigrant visitors. Among the foreign-born, we observed significant differences by immigration status in multidrug resistance (p ϭ 0.02), human immunodeficiency virus (HIV) infection (p ϭ 0.0007), and hospitalization (p ϭ 0.03 for ever/never, 0.01 for duration). Compared with other immigrants, more nonimmigrant visitors were multi-drug-resistant (16 % versus 11% of undocumented residents and 1% of permanent residents), were HIV-positive (32% versus 0% of undocumented and 5% of permanent residents), were hospitalized (47% versus 36% of undocumented and 19% of permanent residents), and had lengthy hospitalizations (median [midspread] days ϭ 87 [25 to 153] versus 8.5 [4 to 28] for undocumented and 10 [7 to 24 d] for permanent residents). We found nonimmigrant visitors to be an important source of tuberculosis morbidity in Tarrant County. Further studies in other regions of the U.S. are needed to determine if screening and treatment recommendations of persons who spend extended periods in the U.S. should be raised to the standards set for permanent residents.
Poor adherence to tuberculosis (TB) treatment hinders the individual's recovery and threatens pub... more Poor adherence to tuberculosis (TB) treatment hinders the individual's recovery and threatens public health. Currently, directly observed therapy (DOT) is the standard of care; however, high sustaining costs limit its availability, creating a need for more practical adherence confirmation methods. Techniques such as video monitoring and devices to time-register the opening of pill bottles are unable to confirm actual medication ingestions. A novel approach developed by Proteus Digital Health, Inc. consists of an ingestible sensor and an on-body wearable sensor; together, they electronically confirm unique ingestions and record the date/time of the ingestion. A feasibility study using an early prototype was conducted in active TB patients to determine the system's accuracy and safety in confirming co-ingestion of TB medications with sensors. Thirty patients completed 10 DOT visits and 1,080 co-ingestion events; the system showed 95. 0% (95% CI 93. 5-96. 2%) positive detection accuracy, defined as the number of detected sensors divided by the number of transmission capable sensors administered. The specificity was 99. 7% [95% CI 99. 2-99. 9%] based on three false signals recorded by receivers. The system's identification accuracy, defined as the number of correctly identified ingestible sensors divided by the number of sensors detected, was 100%. Of 11 adverse events, four were deemed related or possibly related to the device; three mild skin rashes and one complaint of nausea. The system's positive detection accuracy was not affected by the subjects' Body Mass Index (p = 0. 7309). Study results suggest the system is capable of correctly identifying ingestible sensors with high accuracy, poses a low risk to users, and may have high patient acceptance. The system has the potential to confirm medication specific treatment compliance on a dose-by-dose basis. When coupled with mobile technology, the system could allow wirelessly observed therapy (WOT) for monitoring TB treatment as a replacement for DOT.
Chronic cutaneous lupus erythematosus in a linear configuration is rare, particularly in children... more Chronic cutaneous lupus erythematosus in a linear configuration is rare, particularly in children, demonstrating similar incidence in both genders, no photo-sensitivity and lower probability of progression to systemic disease. We describe the case of a 9-year-old girl who presented erythematous papules with central atrophy on the upper and lower right limbs, asymptomatic and following the lines of Blaschko, since age four. Histological examination showed atrophy of the epidermis with aggression from epidermal-dermal interface and periadnexal and perivascular lymphocytic inflammatory infiltrate. Laboratory tests showed ANA in a titer of 1:320, in a dense and fine speckled pattern. Due to the rarity of presentation and location of the disease, this case is reported here.
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