Presenting characteristics as predictors of duration of treatment in sarcoidosis

Background: Some sarcoidosis patients never need therapy, butmany still require therapy more than 2 years after initial diagnosis. Aim: To determine what features at initial presentation areassociated with treatment 2 years later. Methods: Patients with biopsy-confirmed sarcoidosis enrolledin the ACCESS (A Case Control Etiologic Study of Sarcoidosis)study were initially evaluated within 6 months of diagnosis.Pulmonary function, chest X-ray and dyspnoea score were measured,and systemic therapy for the sarcoidosis recorded. Organ involvementwas assessed using a standardized instrument. A subset (n =215) were seen 18–24 months later for follow-up, and thesepatients constitute our study group. Results: Ten patients had only received therapy before the firstvisit, with no further therapy, and were excluded from analysis.Of the remaining 205, 95 were not on therapy at the initialvisit and 75 (79%) of these were never treated during follow-up.Of the 110 initially on therapy, 52 (47%) remained on therapyat follow-up. Other initial features associated with continuedtherapy were the level of dyspnoea and predicted vital capacity.On logistic regression, only dyspnoea and therapy at initialvisit remained significant. Patients on systemic therapy atinitial evaluation were more likely to be on therapy at follow-up(OR 3.6, p = 0.003). Neither ethnicity nor gender independentlypredicted therapy at follow-up. Discussion: This study group represents a sample of newly diagnosedsarcoidosis patients. However, this is a referral population,and there was no set protocol for treatment. Use of systemictherapy within the first 6 months after diagnosis appears tobe strongly associated with continued use of therapy 2 yearslater.     

Beryllium, an adjuvant that promotes gamma interferon production

Beryllium is associated with a human pulmonary granulomatosis characterized by an accumulation of CD4(+) T cells in the lungs and a heightened specific lymphocyte proliferative response to beryllium (Be) with gamma interferon (IFN-gamma) release (i.e., a T helper 1 [Th1] response). While an animal model of Be sensitization is not currently available, Be has exhibited adjuvant effects in animals. The effects of Be on BALB/c mice immunized with soluble leishmanial antigens (SLA) were investigated to determine if Be had adjuvant activity for IFN-gamma production, an indicator of the Th1 response. In this strain of Leishmania-susceptible BALB/c mice, a Th2 response is normally observed after in vivo SLA sensitization and in vitro restimulation with SLA. If interleukin-12 (IL-12) is given during in vivo sensitization with SLA, markedly increased IFN-gamma production and decreased IL-4 production are detected. We show here that when beryllium sulfate (BeSO(4)) was added during in vivo sensitization of BALB/c mice with SLA and IL-12, significantly increased IFN-gamma production and decreased IL-4 production from lymph node and spleen cells were detected upon in vitro SLA restimulation. No specific responses were observed to Be alone. Lymph node and spleen cells from all mice proliferated strongly and comparably upon in vitro restimulation with SLA and with SLA plus Be; no differences were noted among groups of mice that received different immunization regimens. In vivo, when Be was added to SLA and IL-12 for sensitization of BALB/c mice, more effective control of Leishmania infection was achieved. This finding has implications for understanding not only the development of granulomatous reactions but also the potential for developing Be as a vaccine adjuvant.