We report the case of a 38-year-old female patient with systemic lupus erythematosus (SLE) and Jaccoud arthritis (JA) that sequentially developed digital ischemic lesions of the hands. In spite of follow-up treatment with glucocorticoids, immunosuppressant, antiaggregant, and potent vasodilatator agents, a serious progression to digital gangrene over a one-month period was observed. Surprisingly, her nonhealing digital lesions improved after two cycles of rituximab (RTX) administration.
Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that is associated with considerable morbidity and mortality. Digital ischemia, digital ulcer, or gangrenous lesions have been described in SLE [
Presented here is an SLE-JA patient with subluxation of MCPs swan neck deformities who sequentially developed digital ischemic lesions after stopping immunosuppressive treatment at her own discretion due to exorbitant side effects. Digital ischemia of hands showed a serious progression to digital gangrene over a month in spite of follow-up treatment with glucocorticoids, immunosuppressant, antiaggregant, and potent vasodilatator agents.
Surprisingly, her nonhealing ulcers improved dramatically after two cycles of rituximab RTX administration. To the best of our knowledge, this is the first SLE-JA case presenting with nonhealing digital ischemic lesions responding dramatically to RTX therapy in the medical literature.
A 38-year-old Turkish woman with a history of SLE presented in 2003 with photosensitive rash on her face and chest, oral aphthous lesions, and arthritis with pain and motion restriction in hands, wrists, elbows, ankles, and knees. A diagnosis of SLE associated arthritis was made and treatment with 5 mg of prednisone once daily and 200 mg of hydroxychloroquine twice daily was started requiring the addition of methotrexate in escalation until 25 mg weekly was reached. Her joint manifestations were partially responsive; however, arthritis remained active in the small joints of her hands with pain and swelling. Six years later, the patient developed avascular necrosis during follow-up for which she was operated on at an outside setting and a hip prosthesis was implanted.
Two years following surgical treatment for avascular necrosis, the patient presented to our rheumatologic polyclinic with complaints of pain, swelling, warmth, and cyanosis over the fingers of both hand and toe tips. Physical examination revealed swelling, warmth, and tenderness in the proximal interphalangeal (PIP) joints of both hands, Ulnar deviation, and bilateral swan neck deformities. Right is greater than left. “Z” deformities of thumbs (Figure
(a) Right hand with swan neck and Z deformity of the thumb (before treatment). (b) Radiograph; AP of bilateral hands suggesting Jaccoud radiological features. (c) Digital ulcers of the second to fourth digits of the right hand (2 weeks after initial treatment with cyclophosphamide). (d) Unresponsiveness to initial treatment demonstrated by a serious progression from ischemic lesions to digital gangrene lesions of the second to fourth digits of the right hand (one month after initial treatment regimen; cyclophosphamide, corticosteroids, and prostaglandins). (e) Response to treatment observed after first cycle of rituximab therapy (5 months following the start of RTX treatment). (f) Complete remission of digital gangrenous lesions after 2 cycles of rituximab therapy (10th month of the RTX treatment protocol (rituximab, glucocorticoid, aspirin, azathioprine, and hydroxychloroquine)).
Laboratory findings were as follows: WBC:
Immunologic studies revealed an ANA titer of 1 : 3200, (++++, speckled pattern), U1RNP (+++), p-ANCA (+), antibeta 2 GP1-IgA isotype (43,5 U/mL; normal: <5 U/mL). There was hypocomplementemia (C3: 0,647 g/L, C4: 0,0758 g/L; normal: 0.9–2 g/L and 0.1–0.4 g/L, respectively.). ds-DNA and Sm antibodies and rheumatoid factor were negative.
Review of hand radiographs showed no erosive changes consistent with a diagnosis of JA (Figure
Results from laboratory studies showed high disease activity of lupus. Initial treatment was started with glucocorticoid (1 mg/kg/day), aspirin (300 mg/day), IV prostaglandin (2 mcg/kg/min), and IV cyclophosphamide (500 mg/m2).
Unexpectedly, digital ischemia of hands showed a serious progression to digital gangrene (Figure
Following the first month of unsuccessful treatment with the initial treatment regimen, a new treatment protocol including rituximab (RTX) with 2 infusions of 1 g at a 14-day interval in combination with hydroxychloroquine and aspirin was initiated during the second month. Clinical and laboratory response to treatment began to be observed during the third month of RTX therapy. Laboratory evaluation revealed the following: ESR: 22, CRP: 3 mg/dL, and normal levels of C3 and C4 complement levels. (Results from a complete blood count panel were unremarkable). A combining dosage of 100 mg/day azathioprine (AZA) was added to the treatment protocol after two infusions of RTX therapy. Also, corticosteroid dosage which was started at 1 mg/kg was tapered gradually by 10% per kilogram for every 10 days till it reached 5 mg/day over the three-month period.
Eventually, digital gangrenous lesions started to regress after the first cycle (5 months) of RTX therapy (Figure
Vasculitis and digital gangrene have been described in SLE. Thromboembolism, premature atherosclerosis, overlap syndrome, and especially antiphospholipid antibodies (aPLs) may contribute to the development of gangrene [
The prevalence of digital gangrene in APS patients has been reported to be between 3.3 and 7.5% and the presence of a positive anti-RNP has been described in some APS digital ulcer cases [
RTX has been shown to be effective in the reduction of B-cell production and used in the treatment of refractory SLE or vasculitis. In a prospective study conducted by Smith et al., rituximab was shown to play a role in B-cell depletion offering the prospect of sustained disease remission and improved disease control with low toxicity in patients with active refractory SLE or ANCA associated vasculitis (AAV) [
In the presence of Apl/LAC, patients were first anticoagulated with IV heparin or low molecular weight heparin (LMWH) before long-term treatment with warfarin [
In our patient, digital ischemic lesions were seen two years after stopping treatment at her own will. We added a treatment regimen of Iloprost and acetyl salicylic acid to her traditional immunosuppressive agents which included steroids, hydroxychloroquine, and cyclophosphamides. Her nonhealing ulcers however prompted us to start an infusion dosage of 1000 mg rituximab (per 0–15 days) therapy considering its role in B-cell depletion and low toxicity in patients with ischemic lesions. Surprisingly, her digital ulcers responded dramatically to rituximab therapy after 2 cycles and a recession in acute phase markers was observed.
To the best of our knowledge, our case is the first case in the medical literature reporting an SLE-JA association developing digital ischemic lesions as a late clinical complication and responding dramatically to rituximab therapy.
As a conclusion in lupus patients with arthritis associated nonhealing digital ulcers under traditional immunosuppressive agents, RTX can be a treatment option.
The authors declare no conflict of interests.