Effect of indinavir and higher CD4+ T-cell count on viral load response after 6 months of highly active antiretroviral therapy.

This retrospective, unmasked chart review was undertaken to determine which HIV-infected patients receiving protease inhibitors (PIs) for the first time were most likely to experience a decrease in plasma viral load (PVL) and which factors were associated with a PVL < 500 copies/mL below the detectable limits after 6 months. A total of 308 patients aged > 15 years with a PVL > 500 copies/mL received therapy that included a PI in addition to other antiretroviral therapies (128 patients, saquinavir hard-gel capsule 600 mg TID; 107 patients, indinavir 800 mg TID; and 73 patients, ritonavir 600 mg BID). The choice of drug was at individual clinicians' discretion. Patients were followed for a median of 10 (range, 6 to 21) months. Of the 128 patients who received saquinavir, 45% were switched to another PI (33%, indinavir; 12%, ritonavir). Seventy percent of the 73 patients initially given ritonavir were switched (45%, indinavir; 25%, saquinavir), as were 23% of the 107 patients initially given indinavir (15%, saquinavir; 8%, ritonavir). A total of 34.1% (n = 105) of patients achieved a PVL < 500 copies/mL; in 51.6%, PVL decreased > 0.5 log copies/mL. In this subgroup, both treatment-naive patients and those who were receiving a new combination of antiretroviral therapy when they started PI treatment had a more pronounced decline in PVL (P < 0.001). After adjustment by logistic regression analysis for age, sex, mode of transmission, and duration of highly active antiretroviral therapy (HAART), CD4+ cell count and initial type of PI received were independently associated with PVL < 500 copies/mL. In the present study, the treatment success rate was low (34.1%) compared with rates observed in randomized, controlled trials. A higher CD4+ cell count and use of indinavir at the initiation of HAART are associated with a better viral load response.

Distal extremity swelling with pitting edema in psoriatic arthritis: evidence of 2 pathological mechanisms.

Distal extremity swelling with pitting edema due to altered lymphatic drainage has been reported in some patients with psoriatic arthritis (PsA). The edema usually affected the upper limbs in an asymmetric pattern and was resistant to therapy. We describe 2 additional cases. The distal swelling and pitting edema responded promptly and completely to corticosteroids in the first patient but persisted in the second. Lymphoscintigraphy and magnetic resonance imaging (MRI) revealed a predominant tenosynovitis in the hand without lymphedema in the first patient, and impaired lymphatic drainage without tenosynovial sheath involvement in the second. We conclude that 2 different mechanisms, characterized by a different response to therapy, may be associated with the same clinical picture of distal swelling with pitting edema in patients with psoriatic arthritis. Lymphoscintigraphy and MRI are useful in defining the structures involved and in predicting the prognosis.

Behçet's disease with unusual cutaneous lesions.

A variety of cutaneous lesions may occur in Behçet's disease (BD) both at presentation and over the course of the disease. Skin involvement of the hands and feet has been infrequently observed. We describe a patient with BD with recurrent, multiple, papulonodular cutaneous lesions affecting the palm and fingers of both hands, occurring simultaneously with aphthous stomatitis. The lesions consisted of roundish, erythematous, painful, bluish-red nodules, 0.5-1 cm in diameter, with a "pernio-like" aspect. Histologic examination revealed perivascular neutrophilic infiltrates. We suggest that cutaneous lesions with a pernio-like aspect as observed in our patient may be included in the spectrum of the cutaneous manifestations of Behçet's disease.

Possible association between eosinophilic fasciitis and subcutaneous heparin use.

The association between the onset of eosinophilic fasciitis and exposure to a drug or a toxin has occasionally been reported. We describe 3 patients who developed eosinophilic fasciitis a few months after they received subcutaneous calcium heparin. In 2 patients, clinical manifestations and eosinophilia improved after interruption of the therapy. Although spontaneous occurrence of eosinophilic fasciitis cannot be excluded in our patients, the temporal relationship with the beginning of subcutaneous heparin therapy raises the possibility that the syndrome might be precipitated by the drug.

The role of plasminogen activators in alopecia areata.

Plasminogen activators are serine proteinases which transform the serum zymogen, plasminogen, into plasmin, a broad-spectrum protease with fibrinolytic effect. Two main plasminogen activators have been described in humans: urokinase (UK; molecular weight, 55,000) and tissue-type plasminogen activator (tPA; molecular weight, 74,000). Thirteen subjects were studied who had alopecia areata (AA), nine in the active phase and four in remission. There were alterations in the perivascular and peribulbar fibrinolytic activity in the nine subjects in the active phase of disease, suggesting a possible role of plasminogen activators in AA. A modified Todd's autohistographic method was used to evaluate cutaneous fibrinolytic activity (which depended on the activity of plasminogen activators) in the 13 AA subjects and five volunteer controls. Cutaneous fibrinolytic activity was reduced in perivascular areas, but increased in peribulbar areas, in the nine subjects in the active phase of disease. Tests with monoclonal antibodies directed against the catalytic sites of tPA and UK showed that the perivascular fibrinolytic activity was tPA dependent, and the peribulbar fibrinolytic activity was UK dependent.

Fibrinolytic activity in the synovial membrane of osteoarthritis.

The fibrinolytic activity (FA) has been studied on the synovial membrane obtained from 16 patients with osteoarthritis (OA), 20 patients with rheumatoid arthritis (RA) and 11 control subjects. Todd's autohistographic method, modified by Lotti, was used to investigate the FA and the monoclonal antibodies against u-PA and t-PA were used to identify the main plasminogen activator. Our results show that the FA is increased in the synovial membrane of patients with OA in comparison with the synovial FA of control subjects. In the synovial membranes from patients with RA, the FA shows different results: in some specimens FA is increased, and in others it is diminished or similar, compared with FA of samples from healthy controls. Thus, our data on synovial FA in OA confirm the previous reports, performed in vitro, on the activation of the plasmin system in this degenerative disease. The activity of the fibrinolytic system seems to participate in the cartilage degeneration and, via the activation of collagenase, to perpetuate the cartilage damage.