Case of granulocyte colony-stimulating factor-induced Sweet's syndrome.

A 33-year-old male was referred with a two-week history of fevers to 40 degrees C and painful, erythematous skin and oral mucosal eruptions that had failed to respond to multiple anti-infectious agents. He had a recent diagnosis of a "myeloproliferative disorder with myelodysplastic features" on bone marrow biopsy, with associated pancytopenia. Two weeks before admission, he had been treated with a course of granulocyte colony-stimulating factor (G-CSF) at a dose of 300 microg/day in an attempt to improve his neutropenia. After four days of treatment, the fever and lesions developed. Infectious evaluation was negative; however, biopsies of the skin and oral mucosal lesions revealed histology consistent with Sweet's syndrome. Intravenous methylprednisolone (30 mg/day) was started with prompt defervescence and resolution of the lesions within days. With the increasing use of G-CSF, Sweet's syndrome is becoming more commonly recognized as an adverse effect. This is the first case of G-CSF-induced Sweet's syndrome to demonstrate gingival involvement.

Radiation-induced pneumonitis in the "nonirradiated" lung.

OBJECTIVE: To describe six cases of radiation-induced organizing pneumonitis occurring outside the direct radiation field and to review clinical, radiologic, and histologic aspects of this entity. MATERIAL AND METHODS: We present detailed case reports of six women, with a mean age of 62.8 years (range, 50 to 75), who had received radiation therapy (mean dose, 6,560 cGy) for breast cancer. RESULTS: From 6 to 17 months (mean, 8.8) after the completion of radiotherapy, recurrent and migrating lung infiltrates were detected outside the radiation field in the six study patients. Three patients had pronounced respiratory symptoms, whereas the rest were minimally symptomatic or asymptomatic. Thoracic computed tomography showed dense alveolar infiltrates. Bronchoalveolar lavage in two patients revealed lymphocytosis (25% and 19%), and lung biopsy in five patients demonstrated a histologic pattern consistent with bronchiolitis obliterans organizing pneumonia. Even though the symptomatic patients showed prompt resolution of their symptoms and roentgenographic abnormalities after systemic corticosteroid therapy, the lung infiltrates recurred after corticosteroid therapy was discontinued. CONCLUSION: These six cases, including their prompt response to corticosteroid therapy, provide additional evidence that irradiation damages lung tissue outside of the direct treatment field and suggest that an immunologically mediated lymphocytic alveolitis may be responsible for the recurrent migratory organizing pneumonitis.

Immune sensitization augments epithelium-dependent spontaneous tone in guinea pig trachealis.

We examined epithelial modulation of tracheal smooth muscle (TSM) responsiveness in vitro from guinea pigs receiving active immune sensitization in vivo. Initially, guinea pigs were either ovalbumin sensitized (by aerosol) or sham sensitized with normal saline; TSM responsiveness was assessed isometrically as active tension (AT) after equilibration by electrical field stimulation in vitro. For epithelium-intact (Epi+) tissues, sensitization caused an increase in baseline active spontaneous tone (1.89 +/- 0.20 g AT) vs. sham-sensitized tissues (1.18 +/- 0.28 g AT; P = 0.02). Spontaneous tone in sensitized TSM in which the epithelium was removed (Epi-) (1.01 +/- 0.14 g AT) was substantially less than from Epi+ tissues (P = 0.01) and did not differ from sham-sensitized epithelium-denuded tissues (0.82 +/- 0.24 g AT; P > 0.05). Indomethacin caused a reduction in spontaneous tone to comparable magnitude for all treatment paradigms. Immune sensitization caused physiological reduction in the ability to relax in response to isoproterenol; the concentration of isoproterenol eliciting 50% relaxation of spontaneous tone was 7.10 +/- 0.13 (-log M) for TSM from sensitized guinea pigs compared with 8.20 +/- 0.27 (-log M) for sham-sensitized tissues (P = 0.006). However, after precontraction with exogenous acetylcholine, relaxation caused by isoproterenol was not affected by either indomethacin or epithelial removal. Muscarinic responsiveness to acetylcholine was augmented by immune sensitization; however, the increase in response to acetylcholine was attenuated by epithelium removal or cyclooxygenase blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of airway inflammation on smooth muscle shortening and contractility in guinea pig trachealis.

We studied the effect of either 1) immunogenic inflammation caused by aerosolized ovalbumin or 2) neurogenic inflammation caused by aerosolized capsaicin in vivo on guinea pig tracheal smooth muscle (TSM) contractility in vitro. Force-velocity relationships were determined for nine epithelium-intact TSM strips from ovalbumin-sensitized (OAS) vs. seven sham-sensitized controls and TSM strips for seven animals treated with capsaicin aerosol (Cap-Aer) vs. eight sham controls. Muscle strips were tethered to an electromagnetic lever system, which allowed isotonic shortening when load clamps [from 0 to maximal isometric force (Po)] were applied at specific times after onset of contraction. Contractions were elicited by supramaximal electrical field stimulation (60 Hz, 10-s duration, 18 V). Optimal length for each muscle was determined during equilibration. Maximal shortening velocity (Vmax) was increased in TSM from OAS (1.72 +/- 0.46 mm/s) compared with sham-sensitized animals (0.90 +/- 0.15 mm/s, P < 0.05); Vmax for TSM from Cap-Aer (0.88 +/- 0.11 mm/s) was not different from control TSM (1.13 +/- 0.08 mm/s, P = NS). Similarly, maximal shortening (delta max) was augmented in TSM from OAS (1.01 +/- 0.15 mm) compared with sham-sensitized animals (0.72 +/- 0.14 mm, P < 0.05); delta max for TSM from Cap-Aer animals (0.65 +/- 0.11 mm) was not different from saline aerosol controls (0.71 +/- 0.15 mm, P = NS). We demonstrate Vmax and delta max are augmented in TSM after ovalbumin sensitization; in contrast, neurogenic inflammation caused by capsaicin has no effect on isolated TSM contractility in vitro. These data suggest that airway hyperresponsiveness in vivo that occurs in association with immunogenic or neurogenic inflammation may result from different effects of these types of inflammation on airway smooth muscle.

Effect of immune sensitization on stimulated ACh release from trachealis muscle in vitro.

We assessed the effect of immune sensitization on acetylcholine (ACh) release from parasympathetic nerve terminals in tracheal smooth muscle (TSM) strips from ragweed-sensitized (RWS) and sham-sensitized, littermate control (LMC) dogs. Strips of TSM were tethered to force transducers at optimal length in perfusion chambers containing [3H]choline and a fixed volume of physiological perfusate. Tissues were equilibrated for 1 h by electrical field stimulation (EFS) every 5 min to facilitate uptake of label into parasympathetic nerves as ACh. Fresh perfusate (containing 3 x 10(-8) M physostigmine) was collected at 5-min intervals for 1 h, and a rate coefficient of [3H]ACh release was determined. Tissues were exposed to agonists in the seventh collection period, and the increase in label release (ratio change where < or = 1.00 = baseline) and force production were determined. Ragweed antigen challenge stimulated [3H]ACh release and contraction in RWS but not LMC tissues. [3H]ACh release was 1.93 +/- 0.22 x baseline in RWS vs. 0.92 +/- 0.02 in control tissues (P < 0.01); contraction was 31.2 +/- 9.5% of that elicited by EFS (% EFS) in RWS vs. 0% EFS in LMC tissues (P < 0.01). Strips of TSM from RWS but not LMC dogs demonstrated concentration-dependent, augmented release of ACh caused by histamine. After 10(-4) M histamine, [3H]ACh release in RWS was 1.94 +/- 0.37 x baseline vs. 1.05 +/- 0.06 for LMC tissues (P < 0.05); histamine also caused greater contraction in RWS (106.5 +/- 5.9% EFS) vs. LMC (86.5 +/- 5.6% EFS; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)