Interstitial Lung Disease and Pulmonary Hypertension Responsive to Low-Dose Ultraviolet A1 Irradiation in Lupus

Abstract

In three placebo-controlled, double-blind studies, low-dose, full body UVA1 irradiation administered 2-3 times a week had a remedial action in patients with systemic lupus erythematosus (SLE) [1][2][3] . SLE Activity Measure (SLAM) and SLE Disease Activity Index (SLEDAI) scores decreased significantly. The therapy mitigated fatigue, joint pain, rashes, cognitive dysfunction, and photosensitivity within days to weeks, and over the years appeared to maintain these gains 4 . In only one of these studies was an effect on dyspnea recorded, 4/4 patients experiencing decreases 3 . Although the lungs are clearly a target in SLE, there has been no patient with pulmonary disease, prior to this report, monitored for changes in pulmonary measures during prolonged UVA1 irradiation therapy. Case ReportA 39-year-old woman with SLE of five years duration presented with fatigue, a malar rash, polyarthritis, photosensitivity, dyspnea, interstitial lung disease (ILD) and pulmonary hypertension (PH). She had a history also of mouth ulcers, intermittent leukopenia, pericarditis, and recurrent pleurisy. She had an ANA of 1: 640, an IgM anticardiolipin antibody of 21 MPL U/mL (normal: 0-9), an increased anti-RNP, and prior to entering the study, elevated anti-SSA antibodies. Anti-dsDNA antibodies were absent and the sedimentation rate, CRP, and C3 were normal throughout the study. At the outset of the treatment, the C4 was low at 16 mg/dl (normals 18-45) and the WBC 2.7 (×10 3 ), but the C4 became normal and the WBC, ranged from 4-6 (×10 3 ) after the start of therapy. She had been taking 8 mg of methylprednisolone a day and 200 mg of hydroxychloroquine twice daily for over a year. The initiation of low-dose (8J/ cm 2 ) full body, twice weekly exposures to UVA1 irradiation, as previously described 1 , led to resolution of her fatigue and malar rash within days, polyarthritis and cognitive deficits within weeks, and photosensitivity within months, during which she discontinued her prednisone but continued the hydroxychloroquine. Although the study was not directed at interstitial lung disease (ILD) or pulmonary hypertension (PH), over the long term her pleurisy subsided, dyspnea diminished, restricted pulmonary volume increased, and the DLCO as measured by single-breath standard technique increased from 14 to 24 ml/min/mmHg ( Figure), representing a 65% to 105% increase of predicted. Pulmonary pressures, measured by trans-thoracic ultrasound, decreased from 45 to 25 mmHg. Her ANA remained at 1: 640, ENA and anticardiolipin antibodies became negative, and the anti dsDNA, sedimentation rate and CRP remained normal. She gradually discontinued her prednisone and progressed through a successful pregnancy while continuing the UVA1 therapy. Unfortunately, due to an unforeseen and permanent interruption of therapy, her condition deteriorated, the DLCO decreased to 17 mm/min/mmHg ( Figure) and the patient required resumption of corticosteroid therapy. Her lung volumes worsened with pulmonary function studies revealing a mild restrictive defect....

Photosensitivity in cutaneous lupus erythematosus

“…UVA-1 radiation in lupus-prone MRL-lpr mice also prevented development of CLE-like skin lesions (45). Based on these findings, UVA-1 was tested in SLE patients in varying dosing regimens in case report, open-label and randomized control trial settings ( Table 2) (37)(38)(39)(40)(41)(46)(47)(48)(49)(50). In these trials, UVA-1-treated patients demonstrated decreased systemic symptoms and disease activity scores (e.g.…”

Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus

“…Solar UV-B photons isomerize UCA from its resting trans- form to the active cis- isomer, which suppresses CMI. Even the UV-B photons emitted from uncovered fluorescent lamps isomerize UCA to its active cis isomer 13 in vitro and increase disease activity in vivo . 66 Teleologically, the suppression of CMI may serve to protect against solar-mediated actinic changes that would predispose patients to immune-mediated rashes and pruritus with every sun exposure.…”

“…Currently, the only patient with interstitial lung disease (ILD) and pulmonary hypertension (PH) who was treated with UV-A1 irradiation was a 36-year-old Caucasian woman with antinuclear antibody (ANA)/anti-Sjögren syndrome-related antigen A (SSA)-positive lupus for a duration of five years. 13 She had been taking 400 mg of hydroxychloroquine and 6 mg of methylprednisolone for the previous year, without a significant effect. Within weeks of starting triweekly full-body UV-A1 irradiation at 8 J/cm 2 , her symptoms of fatigue, malar rash, polyarthritis, mouth ulcers, and intermittent pleurisy abated.…”

“…A 32-year-old woman with lupus and with high levels of aCL antibodies was treated with long-term, low-dose, full-body UV-A1 irradiation. 13 She had a five-year history of progressive memory loss, diminished concentration, and livedo reticularis. Her IgM aCL antibody level was 44 MPL (IgM phospholipid U/ml, normal range: 0–9 MPL/ml), and her IgA and IgG aCL levels were within normal limits.…”

Human and Murine Evidence for Mechanisms Driving Autoimmune Photosensitivity

“…UVA, UVB, and UVC are divided based on wavelength (UVA = 400–320 nm; UVB = 320–280 nm; UVC = 280–100 nm), with shorter wavelengths associated with higher energy effects. In general the longer wavelengths, such as UVA, which has been shown to have therapeutic potential in SLE patients ( 7 – 9 ), penetrate more deeply in the skin, reaching the dermis, whereas UVB is absorbed almost entirely by the keratinocytes of the epidermis ( 10 ). UVC rarely reaches the skin as it is primarily absorbed by atmospheric ozone.…”