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Eye and/or orbit involvement occurs in Granulomatosis with polyangiitis (GPA) patients frequently. The aim of our study was to describe the clinical manifestations, therapy and outcome of ocular involvement in our GPA patients. A retrospective study was conducted including patients with GPA who followed up in Rheumatology clinics during 1990-2016 at King Khalid University Hospital, Riyadh. Information relating to demographics, ocular manifestations, laboratory findings, therapy and outcome of GPA patients were noted. Ocular involvement was detected in 9 (39.1%) of the 23 GPA cases identified. The mean age of ocular GPA patients was 51.8 (range 27 - 62) years, the mean age at onset of disease was 39.6 (range 11 - 57) years and the mean duration of disease was 9.0 (range 2 - 19) years. Concomitant ear, nose, throat and sino-nasal manifestations occurred with ocular symptoms in 77.8% GPA patients. The most frequent manifestations were, eye pain (66.7%), scleritis/episcleritis (55.6%), eye redness and itching (55.6% each). Antineutrophil cytoplasmic antibodies (ANCA) were positive in 88.9% patients, 55.6% had c-ANCA and 33.3% had p-ANCA. Infections were observed in 22.2% of patients, which included pneumonia in one patient and esophageal candidiasis and bacterial meningitis in another. All patients received oral prednisolone, 44.4% received intravenous cyclophosphamide, 22.2% refractory cases received rituximab doses and the disease outcome was good. Comparison of ocular GPA with non-ocular GPA patients showed that 77.8% of ocular GPA patients had concomitant sino-nasal symptoms compared to 42.9% in non-ocular GPA patients and 22.2% of the ocular GPA patients had renal involvement compared to 64.3% in non-ocular GPA patients (p = 0.049). We found that the frequency of ocular manifestations in our GPA patients was similar to reports elsewhere, and the most frequent symptom was eye pain and scleritis/episcleritis.

Objectives: Granulomatosis with polyangiitis (GPA) affects respiratory system very often. In this report, we document the pulmonary manifestations and computed tomography (CT) findings in GPA patients. Subjects and Methods: We conducted retrospective study of GPA patients followed up at King Khalid University hospital, King Saud University, Riyadh, during the period 1990–2014. Various disease manifestations, X-ray and CT findings, therapy, and outcome in GPA patients with pulmonary involvement were retrieved. Results: Among 23 cases of GPA, 14 were males and 9 were females. Mean age at onset of disease was 42.1 ± 14.5 (range: 11–63) years. Respiratory tract was the most frequently involved system (82.6%); upper airways were affected in 56.5% and lungs in 65.2% patients. Among 19 patients with respiratory system involvement antineutrophil cytoplasmic antibody (ANCA) was positive in 18 (94.7%) patients; c-ANCA was positive in 15 (78.9%) and p-ANCA was positive in 3 (15.8%) patients. Chest CT findings in 15 patients showed that lung nodules were the most frequent pathologies, seen in 12 (80.0%) patients, and were cavitated in 8 (53.3%) patients. Airspace opacification was seen in 73.3%, air bronchogram in 20.0%, and ground-glass opacities in 33.3%. CT results at follow-up showed resolution of lung nodules in 9 (60.0%) patients. Lung biopsies showed chronic granulomatous inflammation with vasculitis and necrosis. Intravenous cyclophosphamide was received by 63.2% patients and 10.5% required rituximab therapy along with other drugs. Conclusion: Respiratory system involvement in our GPA patients was similar to previous reports but with variation in certain parameters. Disease outcome was good, and lung CT at follow-up showed resolution of nodules with treatment.

Objective: To explore clinical and laboratory features, therapy and outcome of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) patients from our tertiary care center. Methods: This study of AAV patients seen in Rheumatology clinics at King Khalid University hospital (KKUH), King Saud University, Riyadh during the period 1990-2014 was carried out retrospectively. Demographic, clinical, haematological and immunological parameters along with therapy, complications and outcome were retrieved from patients' medical charts. Different characteristics were compared between the three groups of AAV; GPA (Granulomatosis with polyangiitis), MPA (Microscopic polyangiitis) and EGPA (Eosinophilic granulomatosis with polyangiitis). Results: We identified 34 AAV patients (21 males: 13 females; 31 Saudis: 3 non-Saudis) comprising of 23 GPA, 2 MPA and 9 EGPA cases. The mean age of onset was 42.1±17.6 years (range 11-75) and mean duration of disease was 8.7± 5.1 years (range 1-20). The most frequently affected system was pulmonary in all AAV (73.5%), GPA (65.2%) and EGPA (100%) while it was renal in MPA (100%) patients. Ophthalmological and upper airways involvement was higher in GPA. Neurological involvement was higher in EGPA (p

Eosinophilic granulomatosis with polyangiitis (EGPA) is an uncommon ANCA associated vasculitic disorder characterized by systemic necrotizing vasculitis of small vessels occurring exclusively among patients with bronchial asthma and tissue eosinophilia. Familial EGPA is extremely rare. Only two case reports have been published so far. We present a Saudi family with 3 cases of EGPA and almost three-fourths of family members affected by asthma. We explored genetic basis of EGPA in this family and found that genes were mutated in four affected siblings suggesting genetic involvement in susceptibility to EGPA.

Granulomatosis with polyangiitis (GPA) formerly called Wegener’s granulomatosis is a chronic necrotizing granulomatous inflammatory disease with systemic vasculitis involving the upper and lower respiratory tract, and kidneys. The typical histopathology is that of necrotizing granulomatous inflammation with palisading histiocytes, neutrophils, and lymphocytes. We report a case of a 57-year-old lady presenting with left eye swelling, left ear pain and discharge, but with no pulmonary or renal symptoms. Investigations revealed positive cytoplasmic antineutrophil cytoplasmic antibodies and proteinase 3 antibodies. The CT and MRI showed meningeal thickening and bilateral structural changes of the orbits and mastoids. Lacrimal gland biopsy showed non necrotizing granulation with an eosinophilic infiltration. She was diagnosed with eosinophilic variant of GPA of the eyes and mastoid bones bilaterally extending to dura and sparing the lungs and kidneys. She responded to corticosteroids and rituximab. Saudi Med J 2016; Vol. 37 (6): 690-693 doi: 10.15537/smj.2016.6.14718

Intravenous cyclophosphamide (IV CYC) has been and still used for treatment of severe manifestations of systemic lupus erythematosus (SLE), a disease occurring predominantly in women. IV CYC has been shown to predispose patients to ovarian failure and adverse pregnancy outcomes. We studied the impact of prior IV CYC treatment on ovarian function and pregnancy in our SLE patients, in terms of amenorrhea, fertility, and pregnancy outcome over a 26-year period. The study included 535 women (319 married), out of which 188 received IV CYC and 347 did not. Sixty-one patients experienced amenorrhea; the rate of amenorrhea in IV CYC user group (28.2 %; n = 53) was significantly higher than that in non-IV CYC group (3.7 %; n = 8) (P

Granulomatosis with polyangiitis (GPA) frequently affects ear, nose and throat (ENT) at disease onset. Our aim was to report on our experience with the ENT manifestations in GPA patients, therapy and outcome. A retrospective study of GPA patients was performed who followed up in Rheumatology clinics at King Khalid University hospital, Riyadh during the period 1990-2016. Demographics, different ENT manifestations, laboratory and diagnostic features, therapy and outcome of GPA patients were retrieved from their medical charts. ENT involvement was observed in 15 (65.2%) of the 23 GPA cases identified. Otologic symptoms were noted in 3 (13.0%), nose and sinus symptoms in 13 (56.5%) and throat symptoms in 3 (13.0%) GPA patients. Epistaxis (39.1%) was the most prevalent nose and sinus symptom followed by sinusitis (30.4%), otitis media and hearing loss were the frequent otologic symptoms, oral ulcers and hoarseness of voice constituted frequent throat symptoms in GPA patients. Of the 15 ENT-GPA patients, 9 were males and 6 were females (male: female; 1.5: 1). Their mean age at disease onset was 33.8 ± 18.3 (range 11-57) years and mean duration of disease was 10.1 ± 5.9 (range 1-20) years. ANCA was positive in 93.3% ENT-GPA patients, 73.3% had c-ANCA and 20.0% had p-ANCA. Infections were noted in 33.3% ENT-GPA patients that included pneumonia, septicemia, esophageal candidiasis, bacterial meningitis and herpes zoster. All patients received oral prednisolone, 60.0% received intravenous cyclophosphamide, 20.0% refractory cases received rituximab doses, and the disease outcome was good. Comparison of ENT- GPA with non- ENT GPA cohort showed that 26.7% ENT-GPA patients had renal involvement compared to 87.5% non ENT-GPA patients (p = 0.009). Our study showed that the frequency of ENT symptoms in our GPA patients was less compared to other studies, and the disease outcome was good. Renal involvement was significantly less frequent in ENT-GPA cohort compared to non ENT-GPA cohort.

Reactive oxygen species (ROS)-modified DNA has been shown to be a better and more discriminating immunogen than native DNA (nDNA) for the production of anti-DNA autoantibodies in SLE (systemic lupus erythematosus). Among ROS, the role of hydroxyl radical (.OH) in the induction of damage and modification of nDNA has been extensively studied while such documentation implicating singlet oxygen ((1)O(2)) in inducing immunogenicity in nDNA leading to the production of anti-double-stranded (ds) DNA autoantibodies in SLE is not yet available. This prospective study was undertaken to evaluate the immunogenicity of healthy human dsDNA modified with (1)O(2) generated by methylene blue plus radiant light. Female rabbits were immunized with (1)O(2)-modified human dsDNA to raise anti-dsDNA antibodies. (1)O(2)-modified anti-dsDNA rabbit immune sera and the (1)O(2)-modified anti-dsDNA rabbit purified immunoglobulin G (IgG) were tested against a variety of dsDNA antigenic substrates through direct enzyme-linked immunosorbent assay (ELISA). The immunogenicity of (1)O(2)-modified human dsDNA was further evaluated by studying its immunoreactivity with SLE patients' sera and SLE patients' purified anti-dsDNA IgG. As compared to healthy human sera, (1)O(2)-modified anti-dsDNA rabbit immune sera as well as the (1)O(2)-modified anti-dsDNA rabbit purified IgG demonstrated a strong affinity towards (1)O(2)-modified human dsDNA(.)(1)O(2)-modified human dsDNA proved to be potentially more immunogenic against SLE patients' whole sera and SLE patients' purified IgG as compared to healthy human sera. Our findings suggest that (1)O(2) may also be inducing immunogenicity in native dsDNA resulting in the production of anti-dsDNA autoantibodies as seen in SLE patients.

This study was conducted to evaluate the frequency and pattern of haematological abnormalities (HA) in SLE patients at the time of diagnosis and last follow-up, and their relationship with organ involvement.This retrospective study included patients who were diagnosed and treated for SLE from 1982 to 2008 at King Khalid University hospital, Riyadh. Demographic and haematological parameters at diagnosis and the last follow-up, disease manifestations, organ involvement and clinical hematological complications were recorded. Association of HA with organ involvement was explored by multivariate analysis.A total of 624 patients (90.7% females, mean age 34.3±11.9 years) were studied. HA were present in 516 (82.7 %) patients at the time of diagnosis. Anemia was the most frequent HA in 63.0% patients followed by lymphopenia in 40.3%, leukopenia in 30.0%, thrombocytopenia in 10.9% and autoimmune hemolytic anemia (AIHA) in 4.6% patients. Deep vein thrombosis and pulmonary embolism were diagnosed in 7.4% and 2.6% patients respectively. After a mean follow-up of 9.3±5.3 years, 329/491 (67%) patients still had some HA present. Anemia remained the most common abnormality (51.7% patients) followed by lymphopenia in 33.1%, and thrombocytopenia in 4.8% patients. Leucopenia was associated with oral ulcers (p=0.021) and alopecia (p=0.031), anemia with renal disease (p=0.017), AIHA with neurological involvement (p=0.003), elevated IgG with malar rash (p=0.027), and low C3 with serositis (p=0.026).HA are very common at the time of diagnosis and during follow-up in SLE, and some of these abnormalities are associated with organ damage. This information may help in better management planning of SLE patients.

The aim of this study was to examine the pregnancy outcomes in patients with systemic lupus erythematosus (SLE) and the effect of SLE flare and treatment on pregnancy outcomes. We performed a retrospective evaluation of all pregnancies occurring in patients with SLE during the 27-year period from 1980 to 2006. Of the 319 women with SLE planning pregnancy after SLE onset, 176 (55.2%) conceived resulting in 396 pregnancies. Live births were significantly lower in proportion (70.2% vs. 85.7%) and more likely to end in fetal deaths (29.7% vs. 14.2%) and preterm births (26.7% vs. 5.8 %) in pregnancies occurring after SLE onset than in pregnancies occurring before SLE onset (p < 0.0001). With respect to different disease manifestations, we found that fetal loss was significantly higher in patients with antiphospholipid (aPL) antibodies than without (p < 0.001). Preterm deliveries were significantly more frequent in patients with lupus nephritis, anti-Ro/SSA antibodies, hypertension, history of intravenous cyclophosphamide treatment and aPL than those without these features (p < 0.05). Neonates with intrauterine growth retardation (IUGR) neonates were more common in hypertensive and Raynaud’s-positive pregnancies (p < 0.05). SLE flares occurred in 30.8% pregnancies. There was increased risk of fetal loss, preterm births and IUGR in pregnancies with SLE exacerbations than without (p < 0.05). Prednisolone was found to improve the rate of live births, although it was also a predictor of prematurity. The predictors of pregnancy loss were lupus nephritis (odds ratio (OR) 7.3), aPL (OR 3.9), and SLE flares in pregnancy (OR 1.9). There was higher risk of preterm deliveries in patients with lupus nephritis (OR 18.9), anti-Ro antibodies (OR 13.9), hypertension (OR 15.7) and SLE flares (OR 2.5). IUGR was found to be associated with hypertension (OR 37.7), Raynaud’s (OR 12.3), and SLE flares (OR 4.2). In conclusion, pregnancies in SLE patients with active lupus nephritis, anti-Ro/SSA antibodies, aPL, hypertension, Raynaud’s phenomenon, active disease at conception and SLE exacerbations are at a higher risk of adverse pregnancy outcomes. It is important to carefully plan pregnancy, and experienced rheumatologists and obstetricians should monitor SLE patients in pregnancy and postpartum.

Patients with SLE carry an increased risk of infection that account for 11–23% of all hospitalized patients and 50% of all SLE patients develop major infections during the course of their disease. Globally Herpes Zoster has been reported as the most frequent viral infection in SLE patients. We determined the clinical spectrum, disease sequelae and the risk factors associated with the development of Herpes Zoster in patients with SLE and their outcomes. Retrospective case control study of Herpes Zoster infections was done in SLE patients between 1982 and 2006. Cases were matched 1:2 to controls for age, race, sex and duration of follow up. Clinical features of the cases from the time of lupus diagnosis to the time of Zoster were compared to their respective controls over similar time periods. Thirty two SLE cases were compared to sixty four controls. Cases were more likely to have received cyclophosphamide ( 𝑃 = . 0 2 2 3 ) and intravenous methylprednisolone pulse therapy ( 𝑃 = . 0 0 2 6 ), MMF ( 𝑃 < . 0 2 ), had leucopenia ( 𝑃 = . 0 4 0 7 ) and hemolytic anemia ( 𝑃 = . 0 3 4 4 ). More cases than controls had lupus nephritis, cerebritis, thrombocytopenia but the differences did not reach statistical significance. The mean oral prednisolone dose and proportion of patients receiving immunosuppressives including pulse methylprednisolone therapy, IV Cyclophosphamide and mycophenolate was significantly higher in patients with active SLE compared to patients with SLE in remission at the time of Herpes Zoster ( 𝑃 < . 0 5 ). Disseminated Zoster developed in patients with active SLE (7/9) compared to patients with SLE in remission (0/23). None of the patients had postherpetic neuralgia or bacterial super infection. Immunosuppressive medications were discontinued at the time of diagnosis of Zoster in 19 of 32 patients and all patients received antiviral medications.There were no permanent neurologic deficits or deaths. We conclude that Herpes Zoster infections occur at increased frequency among patients with SLE and carry significant morbidity. Immunosuppressive therapy and severe manifestations of lupus may be risk factors for the development of Herpes Zoster although not necessarily at the time of disease flare or immunosuppressive therapy. Our study suggests that although Herpes Zoster occurs frequently in patients with SLE, it has a relatively benign course.

Our objective was to study the demographic, clinical, laboratory features, therapy, and outcome of systemic lupus erythematosus (SLE) patients. In this retrospective study, which covered a 27-year period (1980–2006), 624 SLE patients referring to King Khalid University hospital, Riyadh were included. There were 566 females and 58 males (9.8:1) with a mean age of 34.3 (range 8–71) years and mean age at disease onset of 25.3 years (range 0.08–67). The mean disease duration was 9.3 years (range 0.3–30). The most common disease manifestations were hematological abnormalities (82.7%), arthritis (80.4%), and mucocutaneous symptoms (64.3%). The prevalence of malar rash was 47.9%, discoid rash 17.6%, photosensitivity 30.6%, oral ulcers 39.1%, serositis 27.4%, nephritis 47.9%, and neuropsychiatric manifestations 27.6%. Lymphopenia (40.3%), anti-Ro (53.1%), anti-La (26.6%), anti-Sm (41.6%), anticardiolipin IgG (49.7%), and IgM (33.5%) antibodies were highly prevalent. Antinuclear antibodies were detected in 99.7% and anti-DNA in 80.1% patients. Low C3 and C4 were observed in 45.4% and 42.2%, respectively. Therapy included oral steroids (96.2%), IV cyclophosphamide (34.1%) and azathioprine (32.1%) along with other drugs. Long-term remission was achieved in 82.4%, disease was active in 2.6%, renal failure occurred in 4.3% requiring dialysis, 6.7% lost follow up and 4.0% patients died. Infections (48%) and active SLE (36%) were the common causes of death. The 5- and 10-year patient survival rate was 98% and 97%, respectively. This study suggests that, in our patients, SLE manifests with features similar to SLE patients from other Arab countries and Caucasia. In comparison to Caucasians, higher prevalence of anti-Ro antibodies is observed in our study, in some Middle-Eastern and Asian countries; this may likely be due to inter-ethnic variation owing to genetic differences. Our 5-year patient survival rate was similar to that of western countries, while 10-year survival rate was better than that of most places.

The aim of this article is to study the prevalence, clinicolaboratory features, WHO histological types, therapy and renal outcome of lupus nephritis (LN) in Saudi Arabia. During the 27-year-period (1980-2006), 299 (47.9%) cases of LN were identified among the 624 cases of systemic lupus erythematosus (SLE) follow-up at King Khalid University Hospital, Riyadh. The female:male ratio in LN was 8.3:1, with a mean age of 32 years and a mean age of onset of 23 years. The WHO renal histological types were; Class I (1%), Class II (18.1%), Class III (10%), Class IV (37.1%), Class V (11.7%), and Class VI (2.7%). Azathioprine was given to 43.1% and pulse cyclophosphamide to 65.6% in combination with other drugs. Remission was seen in 226 (75.6%) patients, renal flares in 14 (4.7%), end stage renal disease (ESRD) in 27 (9.0%), death in 18 (6.0%), and 14 (4.7%) lost follow-up. The 5- and 10-year patient survival rates in our whole LN cohort by Kaplan-Meier analysis were 96% and 95%, respectively. The survival did not differ significantly in different LN classes nor did it differ significantly during the three periods of presentation (1980-1990, 1991-2000, and 2001-2006; P > 0.05). The risk factors for poor survival were found to be older age at onset (>50-years age; P = 0.034), ESRD (P = 0.000), and low C3 (P = 0.022). The risk factors for progression to ESRD were older age at onset (>50-years age; P = 0.037), hypertension (P = 0.009), elevated serum creatinine (P = 0.000), and proliferative LN (Classes III, IV; P = 0.013, P = 0.039). Different treatment modalities did not have significant effect on survival in the whole LN cohort (P = >0.05). However, pulse cyclophosphamide favored remission in Classes II, III, IV, and V (P = 0.023). The main causes of death were renal failure (50%) and infections (44.4%).