A new strategy of drug treatment in NSAID-unresponsive ankylosing spondylitis: combination of pamidronate and methylprednisolone monthly intravenous infusions on the background of a combination of disease modifying drugs sulfasalazine and methotrexate.

OBJECTIVES: To assess short term efficacy and tolerability of a therapeutic strategy in patients with ankylosing spondylitis (AS) unresponsive to nonsteroidal anti-inflammatory drugs (NSAIDs) or coxibs and unable to take anti-tumour necrosis factor-alpha (anti-TNFalpha) biological treatment. METHODS: Established AS patients were given a background treatment consisting of subcutaneous injections of methotrexate weekly (MTX, dose stepped up to a maximum of 20 to 25 mg), weekly 12-16 mg of methylprednisolone orally 30 mts before methotrexate dose (for nausea prevention), sulfasalazine (SSZ, 1 gm orally twice per day) with folic acid supplementation (5 mg daily except on the day of MTX). Additionally, they were given monthly cycles of intravenous (IV) methylprednisolone 'pulse' (MPP) and pamidronate infusions (MPP 500 mg 3 consecutive days + pamidronate 60 mg in a slow IV infusion on day 2 of the MPP infusion). A minimum of six treatment cycles at monthly intervals were given. Adjunct treatment consisted of 1 gm elemental calcium supplementation, paracetamol 650 mg 'as-and-when-required' for symptomatic pain relief, amitriptyline 10 mg 2 hours before bed time daily. RESULTS: Of a total of 46 intent-to-treat patients, 39 patients achieved ASAS-20 and BASDAI-50 response (85%, 95% CI, range 71% to 94%); 7 (15 %) patients failed to improve. The expense involved in 6 months of treatment was approximately 10-fold less than anti-TNFalpha treatment over the same period of time. CONCLUSION: For AS patients unresponsive to standard NSAIDs/coxibs and unable to take anti-TNF biological agents a combination therapeutic strategy showed efficacy and good tolerability in a majority of patients evaluated over a short-term.

Henoch-Schönlein's purpura in adults versus children/adolescents: A comparative study.

OBJECTIVE: To assess the possible differences in etiological and clinical factors between children/adolescents (< or = 20 years) and adults (> 20 years) with Henoch-Schonlein purpura (HSP). METHODS: A retrospective-cum-prospective study of consecutive patients with HSP who presented to our teaching hospital over 5 years. Patients were classified as having HSP according to the criteria proposed by Michel et al and the ACR criteria. RESULTS: 102 patients (43 of all patients being male and 59 female) were classified as having HSP; 20 of the patients were adults (mean age 32.1 +/- 11.7 years) and 82 were children/adolescents (mean age 6.2 +/- 2.6 years). We were unable to identify any precipitating event in 40% of the adults and 37% of the children/adolescents. The frequency of previous drug treatment and of previous upper respiratory tract infection was similar in both groups. At symptom onset, palpable purpura was the chief clinical manifestation in both groups. However, renal involvement, in all its aspects, was more frequent and severe in adults. Adults also had a higher frequency of diarrhoea (with or without occult blood) and leucocytosis, but a lower frequency of thrombocytosis. The frequency of joint manifestations, nausea, vomiting, malena/hematochezia and intussuseption was equal in both groups. Adults required more aggressive therapy, and had a longer hospital stay (10.2 vs. 4.3 days). The outcome was relatively worse in adults, with complete recovery in 18 adults (90%) compared to 81 children/adolescents (98.8%) after a mean +/- SD follow up of 2.8 +/- 1.7 and 2.4 +/- 1.3 years, respectively. CONCLUSION: In adulthood, HSP is a more severe clinical syndrome, with a higher frequency of diarrhoea and renal involvement. Adults also require aggressive treatment more frequently and have a longer hospital stay.

Refractory thrombocytopenia in antiphospholipid syndrome.

Thrombocytopenia is the second most common manifestation of antiphospholipid syndrome (APS). It is found in approximately 22% of the patients with this disease. Often it is not severe, platelet counts usually range between 50 x 10(9)/L and 150 x 10(9)/L without bleeding problems. Yet, it does not protect patients against thrombotic events. It rarely requires treatment and, due to similarities to idiopathic thrombocytopenic purpura (ITP), similar treatment rules usually apply. In this report two patients with APS are described who presented with severe thrombocytopenia that did not respond to standard treatment regimen namely glucocorticoids (GC) followed by intravenous immunoglobulin therapy (IVIG). Splenectomy had to be resorted to relieve the condition.

Systemic lupus erythematosus in Kuwaiti children: organ system involvement and serological findings.

The course and severity of systemic lupus erythematosus (SLE) in children is generally similar to the adult form with potential serious organ system involvement, there are, however, factors that influence the prevalence and clinical behavior of the disease. Our objective was to analyse the organ system involvement and immunological findings in Kuwaiti children with SLE in relation to gender and age of onset and compare these findings to that in published reports. Organ system involvement and serologic profiles were analysed in 35 children with SLE. The major organ systems studied were: renal, hematological, cardiac, pulmonary, hepatic and the central nervous system. The prevalence of ANA, anti-dsDNA, anti-Sm, SSA, SSB and anti-cardiolipin antibodies were studied in addition to complement C3 and C4 levels. The results showed that a high percentage of children had hematological involvement (34%); thrombocytopenia (23%) and hemolytic anemia (20%). Renal involvement was proven by biopsy in only 10 children (29%). Neuropsychiatric manifestations were seen in five (14%) of patients. Males had a tendency for major organ involvement relative to females. All patients had positive ANA tests. All males had positive anti-dsDNA tests compared to 86% of female patients. The most significant finding in this study is the high frequency of hematological manifestations and the relatively low incidence of renal disease and neuropsychiatric abnormalities in Kuwaiti children with SLE.

Deferiprone, efficacy and safety.

OBJECTIVE: Deferiprone (L1), the new oral iron chelator has been studied in several countries for its efficacy and toxicity with some conflicting observations. Toxicity involving joints has been reported more frequently in Indian patients. The authors planned to include larger number of Indian thalassemics in studying safety and efficacy of Deferiprone. METHODS: Seventy five thalassemic children (4-14 yr) were studied for one year with various investigations done periodically. Thirty patients (group A) received 50 mg/kg dose and 21 others (group B) received 75 mg/kg dose of Deferiprone. Rest of the patients were followed up without any chelator. RESULTS: The serum ferritin levels reduced significantly in both groups (P < 0.01 each); more in 75 mg/kg than the 50 mg/kg group. Arthropathy appeared in 15 (50%) patients in Group A and 6 (28.6%) of Group B after 1-12 (mean 6) months of L1 treatment; however, only one patient needed withdrawal of L1. Eleven patients needed indomethacin for pain relief. Seropositivity for antinuclear factor and rheumatoid factor had no relation to dose or duration of L1 therapy, arthropathy or the serum ferritin level. Twelve patients developed leucopenia (< 3.0 x 10(9)/L) and neutropenia (0-1.8 x 10(9)/L) after 2-11 months of L1 therapy and was not related to the dose or duration of therapy. The drug was restarted in 10 patients and only one of them developed a second episode of neutropenia. CONCLUSION: Deferiprone is an effective iron chelator, but arthropathy and neutropenia are very frequent side effects and need strict monitoring during therapy. Most of the neutropenia are neither very severe nor recur with re-challenge with the drug. Similarly, arthropathy does not need withdrawal of drug in majority of patients.

Arthritis associated with tuberculosis.

There has been a resurgence in tuberculosis (TB) worldwide. Approximately 2 billion people have latent infection, 8 million would develop active TB annually, and 2-3 million would die due to TB. With this resurgence, cases with extrapulmonary TB have also shown an increase. Approximately 10-11% of extrapulmonary TB involves joints and bones, which is approximately 1-3% of all TB cases. The global prevalence of latent joint and bone TB is approximately 19-38 million.TB arthritis most commonly manifests as a monoarthritis of weight-bearing joints in the hip or the knee. Oligo- or polyarticular presentation is not rare and may cause diagnostic confusion with inflammatory arthritis. Owing to the low incidence in developed countries, the diagnosis of joint and bone TB is often delayed. A high degree of sensitivity to this diagnosis would prevent delays, permitting prompt institution of anti-TB therapy and preventing irreversible joint damage. Despite advances, confirmation of diagnosis still relies on lengthy microbiological techniques or invasive biopsy. Due to the frequency of isoniazid resistance, initial treatment at present typically includes a combination of four drugs: isoniazid, rifampicin, pyrazinamide and streptomycin or ethambutol. Antimicrobial therapy should be of at least 9 months duration, longer in children and immunocompromised hosts. Surgical procedures should be restricted to joints with severe cartilage destruction, large abscesses, joint deformity, multiple drug resistance or atypical mycobacteria.

Effect of methotrexate on pulmonary function in patients with rheumatoid arthritis--a prospective study.

If given in high doses, methotrexate (MTX), a folate antagonist, could cause pulmonary complications. To evaluate the pulmonary effects of low-dose methotrexate, 55 newly diagnosed patients with rheumatoid arthritis (RA) prescribed with MTX were studied prospectively. A significant reduction in percent predicted values of forced expiratory volume (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), and functional residual capacity (FRC) was observed after 2 years of MTX treatment. A significant increase in the FEV(1):FVC ratio was also observed. In comparison to the normal annual decline in healthy adults, the actual reduction in observed values in the patients was significantly greater (3.2, 6.3, and 6.7 times normal for FEV(1), FVC, and TLC, respectively). PaO(2) and oxygen saturation showed marginal but significant improvement. It was concluded that low-dose MTX treatment in RA might cause an accelerated decline in lung function. Therefore, periodic monitoring of pulmonary function among RA patients started on MTX could be necessary.

Long-term outcome of undifferentiated spondylarthropathy.

Undifferentiated spondylarthropathy is one of the common disease subsets in the group of so-called seronegative spondarthritides. It is not exactly known how often it differentiates into ankylosing spondylitis or other well-defined disease subsets over time. The present study was designed to find out the long-term outcome in this subset. Thirty-five patients diagnosed with undifferentiated spondylarthropathy between January 1987 and December 1988 were recruited. Twenty-two (63%) of them were available for detailed assessment 11 years after the original diagnosis. Their baseline characteristics did not differ from those of the original cohort of 35 patients and were as follows: male:female ratio 19:3, median age of onset 17 years (range 8-39), and median duration of disease 8 months (range 4-24). Clinical features were enthesitis (45%) and inflammatory pain in the back (100%), buttock (77%), hip (64%), shoulder (18%), knee (82%), ankle (77%), and hand and wrists (50%). There was no restriction in spinal movement. Family history was positive in two cases. Radiologically, the only finding was grade I sacroiliitis in 17 patients (77%). Human leukocyte antigen (HLA)-B27 was positive in all. Functionally, all were in class I. During follow-up, one patient developed psoriatic skin lesions after 9 years. Uveitis developed in four patients (18%). After a median follow-up of 11 years, 15 (68%) had ankylosing spondylitis, one developed psoriatic arthritis, four remained undifferentiated, and two had natural remission. Functionally, 19 patients (86%) were in class I and three (14%) were in class III. No patient had bamboo spine, but three underwent total hip replacement. Thus, a majority of patients (68%) with undifferentiated spondylarthropathy gradually developed ankylosing spondylitis of mild severity.

Systemic lupus erythematosus with polyglandular autoimmune syndrome type II: report of an unusual case.

A patient with systemic lupus erythematosus (SLE) is described who had associated autoimmune thyroiditis with subclinical hypothyroidism and idiopathic Addison's disease. The presence of autoimmune thyroid disease and Addison's disease could classify her as having polyglandular autoimmune syndrome (PGAS) type II, which is the commonest of the three types of this syndrome. However, the additional presence of SLE in PGAS type II has not been described earlier. This patient appears to be the first such case.

Calcium pyrophosphatase dihydrate (CPPD) crystal deposition disease in a teaching hospital in Kuwait.

OBJECTIVE: A Medline electronic search showed a paucity of reports on calcium pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) from the Gulf region. To date only a single case report has been published from this region. Therefore, this study aimed, firstly, at finding out the prevalence of chondrocalcinosis in adult Arabs in Kuwait presenting with knee arthritis and, secondly, at carrying out an observational study of CPPD-CDD among Arabs in Kuwait. METHODS: For the study of the prevalence of chondrocalcinosis 100 consecutive adult patients presenting with knee arthritis were radiologically examined. For the observational study the clinical, laboratory, and radiological findings were analysed in patients with CPPD-CDD seen over a period of five years. RESULTS: This study showed the presence of chondrocalcinosis in two (2%) of the 100 adult Kuwaiti and other Middle-Eastern Arab patients (70 men, 30 women, median age 50 (range 45-80)) who presented to the rheumatology clinic for the evaluation of knee pain. When the younger age of the group (only three patients aged >70) is taken into account the figure was comparable with that reported from Western countries. Over a period of five years a total of 2726 new patients were evaluated at the rheumatology clinic of this institution. A diagnosis of crystal arthritis was made in 85 patients (3%). Fourteen of these 85 (that is, 16.5%, but 0.5% of the total cases) were diagnosed with definite (eight patients) or probable (six patients) CPPD-CDD. Different clinical presentations, including that of acute monarthritis (that is, pseudogout), premature generalised osteoarthritis, and polyarticular rheumatoid-like presentations, were seen in different patients. Overlap with true gout, with the additional presence of monosodium urate crystals in the joint aspirate, was seen in two patients. CONCLUSION: The present report shows that CPPD-CDD may not be uncommon among Arabs in the Gulf region. A high degree of clinical awareness and routine examination of joint aspirates with careful analysis for crystals may make it a more common diagnosis in this part of the world. In this regard it is interesting to note that cases and case series including familial cases have been reported from North Africa, especially Tunisia, indicating that the disease has been well described in Arabs of other geographical regions.

Wegener's granulomatosis in India: clinical features, treatment and outcome of twenty-five patients.

OBJECTIVE: To report our clinical experience on Wegener's granulomatosis (WG). METHODS: A retrospective review of case records of all patients with WG in our Rheumatology Clinic during the period July 1988 to June 2000 was carried out and the details of demography, clinical and laboratory data, treatment and outcome were obtained and analysed. RESULTS: Twenty-five patients (16 females and 9 males) were found eligible for inclusion in the study. The mean age and duration of symptoms at presentation were 33.5 years and 5.5 months, respectively. Two patients had limited WG. Twenty-two patients with generalized WG were treated with standard regimen comprising oral prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). Cyclophosphamide was continued for at least one year after the patient attained remission. One patient was treated with intravenous cyclophosphamide regimen. The two patients with limited WG were treated with oral prednisolone and methotrexate (10-12.5 mg as a single dose per week). Remission was achieved in 24 patients after a median time of six months. The median follow-up of patients was five years (range 4 months-11 years). Five patients were lost to follow-up. Eight patients suffered a relapse. The mean time for relapse was 34 months after the initial remission. Seven out of eight patients remitted again after reinstitution of the initial induction regimen. One patient died of diffuse pulmonary haemorrhage despite early institution of therapy. CONCLUSION: WG is being increasingly diagnosed in India now because of greater awareness and diagnostic aids. Although remissions are easy to achieve, relapses continue to pose a challenge to the treating physician.

Hypergammaglobulinemic purpura of Waldenström: report of 3 cases with a short review.

Benign hypergammaglobulinemic purpura of Waldenström (HGPW) is an uncommon cause of non-thrombocytopaenic purpura that may create diagnostic difficulties. The presence of constitutional symptoms associated with prominent immunological abnormalities may raise alarm, leading to extensive and often unnecessary investigations. This report describes 3 young women with HGPW. Clinical features were characterised by recurrent episodes of bilateral asymmetrical palpable purpuric lesions on the lower extremities that were precipitated by a prolonged increase in hydrostatic pressure (e.g. prolonged standing, tight stockings etc.) associated with constitutional features. In one patient the condition was secondary to Sjögren's syndrome with type IV renal tubular acidosis. Laboratory abnormalities included a persistently elevated erythrocyte sedimentation rate, marked polyclonal hypergammaglobulinemia, and high titers of rheumatoid factor and anti-nuclear antibody of the anti-SSA (anti-Ro)/anti-SSB(anti-La) subsets. This topic is reviewed briefly with the emphasis that in its 'primary' form this condition could be considered a 'benign' systemic immunoinflammatory disease that requires neither extensive investigations nor any aggressive form of therapy. Greater awareness of HGPW may increase the frequency of its diagnosis, especially in the patient group with non-thrombocytopenic purpura or the so-called cutaneous vasculitic syndromes with 'palpable purpura'.