Drug‐induced lupus and autoimmune hepatitis secondary to infliximab for psoriasis

We describe a case of previously unreported autoimmune hepatitis and lupus‐like syndrome induced by infliximab treatment for chronic plaque psoriasis. The condition resolved after withdrawal of infliximab, with the liver injury having been reversed and minimal periportal fibrosis. In a two‐part discussion we review the current literature on the pharmacology of infliximab and provide recommendations for management of infliximab side effects.     

Treatment of alopecia areata: An Australian expert consensus statement

Alopecia areata (AA) severity varies from a single small patch to complete loss of scalp hair, body hair, eyelashes and eyebrows. While 40% of all affected individuals only ever get one patch and will achieve a spontaneous complete durable remission within 6 months, 27% will develop additional patches but still achieve complete durable remission within 12 months and 33% will develop chronic AA. Without systemic treatment, 55% of individuals with chronic AA will have persistent multifocal relapsing and remitting disease, 30% will ultimately develop alopecia totalis and 15% will develop alopecia universalis. The unpredictable course and psychological distress attributable to AA contributes to the illness associated with AA. Numerous topical, intralesional and systemic agents are currently used to treat AA; however, there is a paucity of data evaluating their use, effectiveness and tolerability. Topical therapy, including topical glucocorticosteroids, minoxidil and immunotherapy, can be used in cases of limited disease. There are no universally agreed indications for initiating systemic treatment for AA. Possible indications for systemic treatment include rapid hair loss, extensive disease (≥50% hair loss), chronic disease, severe distress or a combination of these factors. Currently available systemic treatments include glucocorticosteroids, methotrexate, ciclosporin, azathioprine, dapsone, mycophenolate mofetil, tacrolimus and sulfasalazine. The optimal treatment algorithm has not yet been described. The purpose of this consensus statement is to outline a treatment algorithm for AA, including the indications for systemic treatment, appropriate choice of systemic treatment, satisfactory outcome measures and when to discontinue successful or unsuccessful treatment.     

Impact of a T cell-based blood test for tuberculosis infection on clinical decision-making in routine practice

New T cell-based blood tests for tuberculosis infection could improve diagnosis of tuberculosis but their clinical utility remains unknown. We describe the role of the ELISpot test in the diagnostic work-up of 13 patients presenting with suspected tuberculosis in routine practice. Of the seven patients with a final diagnosis of active tuberculosis, all were positive by ELISpot including three with false-negative tuberculin skin test results. Rapid determination of tuberculosis infection by ELISpot accelerated the diagnosis of tuberculosis, enabling early treatment initiation.     

Primary lymphedema with coarctation of the aorta: Possible new syndrome or variant of Irons–Bianchi syndrome?

We present a boy with congenital lymphedema, a congenital heart defect (coarctation of the aorta), and mild dysmorphic features. Clinical impression and targeted investigations ruled out Noonan syndrome and Milroy syndrome, but it was not clear whether or not he had Irons-Bianchi syndrome. We discuss the genomic and lymphoscintigraphy evaluation of this case, and review whether the small number of current case reports represent the original Irons-Bianchi syndrome or variants. We anticipate that ongoing molecular investigations such as Next Generation Sequencing will delineate a currently clinically defined phenotypic spectrum.     

Frequencies of Region of Difference 1 Antigen-Specific but Not Purified Protein Derivative-Specific Gamma Interferon-Secreting T Cells Correlate with the Presence of Tuberculosis Disease but Do Not Distinguish Recent from Remote Latent Infections

The majority of individuals infected with Mycobacterium tuberculosis achieve lifelong immune containment of the bacillus. What constitutes this effective host immune response is poorly understood. We compared the frequencies of gamma interferon (IFN-γ)-secreting T cells specific for five region of difference 1 (RD1)-encoded antigens and one DosR-encoded antigen in 205 individuals either with active disease (n = 167), whose immune responses had failed to contain the bacillus, or with remotely acquired latent infection (n = 38), who had successfully achieved immune control, and a further 149 individuals with recently acquired asymptomatic infection. When subjects with an IFN-γ enzyme-linked immunospot (ELISpot) assay response to one or more RD1-encoded antigens were analyzed, T cells from subjects with active disease recognized more pools of peptides from these antigens than T cells from subjects with nonrecent latent infection (P = 0.002). The T-cell frequencies for peptide pools were greater for subjects with active infection than for subjects with nonrecent latent infection for summed RD1 peptide pools (P ≤ 0.006) and culture filtrate protein 10 (CFP-10) antigen (P = 0.029). Individuals with recently acquired (<6 months) versus remotely acquired (>6 months) latent infection did not differ in numbers of peptide pools recognized, proportions recognizing any individual antigen or peptide pool, or antigen-specific T-cell frequencies (P ≥ 0.11). The hierarchy of immunodominance for different antigens was purified protein derivative (PPD) > CFP-10 > early secretory antigenic target 6 > Rv3879c > Rv3878 > Rv3873 > Acr1, and the hierarchies were very similar for active and remotely acquired latent infections. Responses to the DosR antigen α-crystallin were not associated with latency (P = 0.373). In contrast to the RD1-specific responses, the responses to PPD were not associated with clinical status (P > 0.17) but were strongly associated with positive tuberculin skin test results (≥15-mm induration; P ≤ 0.01). Our results suggest that RD1-specific IFN-γ-secreting T-cell frequencies correlate with the presence of disease rather than with protective immunity in M. tuberculosis-infected individuals and do not distinguish recently acquired asymptomatic infection from remotely acquired latent infection.The immune response is responsible for both bacillary containment in latent tuberculosis infection (LTBI) and immunopathology in active tuberculosis (TB). Comparing key immune responses for these two states may therefore help us dissect which responses mediate or correlate with disease and protection. It is therefore of particular interest to compare the immune responses in individuals with latent infection, who have successfully achieved immune control, and individuals with active disease, in whom the immune response has failed to contain the bacterium but immunopathology is present.Gamma interferon (IFN-γ) is essential for controlling Mycobacterium tuberculosis infection (11, 17), and CD4⁺ IFN-γ-secreting T cells specific for mycobacterial antigens play a pivotal role (16, 31). Responses to region of difference 1 (RD1)-encoded antigens are of special interest because of the unique features of early secretory antigenic target 6 (ESAT-6) (1, 30) and culture filtrate protein 10 (CFP-10) (3, 5), which appear to be both virulence factors and putative targets of protective immunity.In a primary bovine TB infection, ESAT-6-specific IFN-γ production, although not a proliferative response, correlated with the severity of disease pathology (39). Likewise, increased ESAT-6 expression and CFP-10 expression in Mycobacterium bovis bacillus Calmette-Guerin (BCG) or Mycobacterium microti infections were associated with increased pathogenicity in susceptible mice and correlated with increased RD1-specific T-cell responses (9). However, RD1-specific responses induced by vaccination are associated with protective immunity against subsequent challenge with virulent organisms. Thus, mice infected with M. tuberculosis were resistant to reinfection (2), and protection correlated with accelerated accumulation of IFN-γ-secreting effector T cells responding to Ag85 and ESAT-6 (1). Mice (27) and guinea pigs (8) vaccinated with BCG::RD1 developed strong CD4⁺ IFN-γ and proliferative responses to ESAT-6. When challenged, these animals had superior protection compared with BCG-vaccinated or unvaccinated mice, as well as less severe pathology and reduced dissemination of the pathogen (32).However, the relationship between the magnitude of ESAT-6 responses and disease in humans is unclear; little is known about CFP-10, and almost nothing is known about the other RD1-encoded antigens. The chaperone protein α-crystallin (“Acr1,” “Rv2031c,” “HspX,” “16-kDa antigen”) is upregulated under oxidative stress conditions (41) and is important for growth in macrophages (12). Encoded by the M. tuberculosis “dormancy regulon” expressed during natural infection (25), this protein is upregulated during conditions of in vitro stress (35). For these reasons, it has been postulated that Acr1-specific T-cell responses may correlate with latency (12, 41).We recently recruited a cohort of 389 individuals suspected to have TB as part of a prospective study of the diagnostic utility of enzyme-linked immunospot (ELISpot) responses to RD1 antigens. (13). A total of 205 patients were given a definitive diagnosis of active or latent TB and had not received antituberculous chemotherapy. We enumerated IFN-γ-secreting T cells specific for ESAT-6, CFP-10, Rv3879c, Rv3878, Rv3873 (10), and purified protein derivative (PPD) and, in a subset, IFN-γ-secreting T cells specific for Acr1. We compared responses to these antigens in patients with active TB and patients with LTBI in a blinded, prospective manner to address the following questions. Are the frequencies of IFN-γ-secreting T cells specific for RD1 antigens, PPD, and Acr-1 different in patients with active TB and patients with LTBI? Do the breadth of the response to RD1-derived peptides in patients with active disease and the breadth of the response to RD1-derived peptides in patients with latent infection differ? Are the hierarchies of immunodominance similar? Do these responses vary with the tuberculin skin test (TST) results? Do responses differ between recently and remotely acquired latent infections?(Part of this work was presented at the winter meeting of the Acid Fast Club, United Kingdom, on 12 January 2007.)     

Retrospective study of oral lichen planus and allergy to spearmint oil

Oral lichen planus (OLP) is a chronic inflammatory disorder with significant morbidity, associated with symptoms of pain and local discomfort. The concept of contact allergy aggravating or inducing OLP is recognised, and reported allergens include amalgam, metals used in dental restoration and flavourings. To date there has been only one case report of a contact allergy to spearmint oil in a patient with a 3‐year history of OLP. We retrospectively reviewed our positive spearmint oil patch test data at the Skin and Cancer Foundation Victoria over a period of 11 years. In total 73 patients of the 1467 tested for allergy to spearmint oil had positive patch tests. The total number of patches tested during this time was 6134. Of the 73 positive reactions, 19 (26%) were classified as relevant, in that the patients had a history of using spearmint oil‐containing products. Coexisting OLP and a spearmint allergy were found in 14 of these 19 patients. All patients had erosive OLP and were female. Patients, especially women, with OLP recalcitrant to treatment should be patch tested to flavourings, especially spearmint oil. We believe that spearmint allergy should be considered a cause of OLP, or at least, of oral lichenoid reactions.