Lower extremity malignancies masquerading as ulcers

Ulcers of the lower extremities, particularly in individuals >65 years old, are a common cause for visits to the podiatrist, wound care specialist, primary care physician, vascular surgeon, or dermatologist. When an ulcer does not respond to adequate medical and wound care, the potential for an underlying malignancy should be considered. Cutaneous malignancies that may masquerade as ulcers include nodulo-ulcerative basal cell carcinoma, squamous cell carcinoma, keratoacanthoma, nodular melanoma, tumor stage mycosis fungoides, lymphomatoid granulomatosis, lymphomatoid papulosis, angiosarcoma, and cutaneous metastases from internal malignancy. It is crucial for healthcare providers to recognize these presentations and render appropriate therapeutic intervention.     

Are leg ulcers in rheumatoid arthritis due to vasculitis?

Five patients with severe rheumatoid arthritis are reported in whom leg ulcers were not apparently associated with vasculitis. The conventional explanation for these ulcers deserves review. Patients with rheumatoid arthritis may develop 'gravitational' leg ulceration and pressure sores on their legs. In addition, they may develop ulcers on the lower aspects of the legs and around the ankles which are well demarcated, punched out, painful and slow to heal. These ulcers usually occur in patients with longstanding, severe, seropositive disease. They are presently considered to be due to a necrotising arteritis causing dermal infarction, since they are frequently associated with other clinical features of rheumatoid vasculitis. Wilkinson has commented that 'biopsies are seldom taken from leg ulcers'. In this paper we report five patients with severe rheumatoid arthritis who developed such leg ulcers in the absence of other clinical evidence of vasculitis and in whom biopsies of the ulcers failed to reveal vasculitis. A case is summarised as illustrative of the five patients, whose relevant histories, clinical findings, and laboratory investigations are summarised in Table 1.     

Class specific rheumatoid factors in rheumatoid arthritis: response to chrysotherapy and relationship to disease activity

IgG rheumatoid factors (RF) may play an important role in the pathogenesis of rheumatoid arthritis (RA). Our study investigates the relationship between class specific RF levels measured by radioimmunoassay and disease activity in patients with RA undergoing chrysotherapy. Nineteen patients were treated with 20 mg disodium aurothiomalate weekly for 6 months. Rheumatoid disease activity was assessed before and after 6 months' treatment and the level of IgG, IgA and IgM RF measured. There were significant falls in disease activity (p less than 0.005), IgA RF (p less than 0.005) IgG RF (p less than 0.005) and SCAT (p less than 0.025), but not IgM RF, over the 6 month treatment period. No correlation was found between absolute levels of IgA, IgG or IgM RF and disease activity before or after 6 months' therapy but there was a highly significant linear correlation between reduction in IgG RF levels and fall in disease activity (r = 0.642, p less than 0.005) with treatment.     

Myelodysplastic features in juvenile rheumatoid arthritis

We have attempted to investigate the dysplastic changes in the hematopoietic system associated with juvenile rheumatoid arthritis (JRA) and its relation to disease activity. The peripheral blood smear and bone marrow aspiration samples of 17 JRA patients were investigated and correlations with laboratory parameters of disease activity sought. The age range was 6–16 years and the duration of disease 1.5–108 months. Abnormal finding of the peripheral smear and bone marrow were scored separately. The score of pathological peripheral blood findings correlated significantly with CRP and ferritin (both P <0.05). In the bone marrow specimens marked changes were noted in the myeloid, erythropoietic, and megakaryopoietic series; however, the score of pathological findings did not correlate with laboratory parameters of disease activity (P > 0.05). We suggest that JRA is associated with marked myelodysplastic changes, also manifested in the peripheral blood smear; these changes may well be the consequence of the inflammatory milieu, including cytokines, during active disease. Am. J. Hematol. 54:166–169, 1997 © 1997 Wiley-Liss, Inc.     

Blunted erythropoietin response to anaemia in rheumatoid arthritis

The relationship of serum immunoreactive erythropoietin to haemoglobin concentration was defined for 54 patients with rheumatoid arthritis (RA) and 41 patients with anaemia of varying aetiology (excluding pregnancy and renal insufficiency), not associated with RA. Significant inverse correlations between the logarithm of serum immunoreactive erythropoietin and the haemoglobin concentration were noted for the anaemic patients in both groups. The regression line for the RA patients had a similar slope, but a significantly lower y-intercept as compared to that for the non-RA patients. Erythropoietin levels were also significantly lower for the group of RA patients than for the group of non-RA patients when matched for comparable haemoglobin concentrations. These studies suggest that the erythropoietin response to anaemia in RA is intact but blunted relative to that for anaemia of other aetiologies. Lower levels of serum erythropoietin in anaemic RA patients may contribute to the pathogenesis of their anaemia.     

Immunologic reactivity in rheumatoid arthritis response to mitogens

The in vitro responsiveness of peripheral blood lymphocytes to a variety of mitogens was compared in cells from normal volunteers, from patients with rheumatoid arthritis and from patients with degenerative joint disease (osteoarthritis). A consistent and marked depression in the proliferative response to Conconavalin A was noted, while statistically comparable results were obtained with PHA and allogeneic lymphocytes. The significance of these observations is discussed with particular reference to a possible discrete defect in a subpopulation of T cells in these patients.     

Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia

Serum immunoreactive erythropoietin (EP) levels were measured in 116 patients with rheumatoid arthritis (RA) and 20 control patients with iron deficiency anemia. Serum EP levels were significantly higher in the 46 anemic RA patients than in the 70 nonanemic RA patients (mean ± 1 SD 31.0 ± 19.8 mU/ml versus 16.8 ± 12.4 mU/ml; P < 0.0001). Furthermore, although a significant inverse correlation between the serum EP level and the hemoglobin value was present in the anemic RA patients (r = −0.57, P < 0.0001), the regression coefficient describing the relationship between serum EP and hemoglobin was significantly lower for the anemic RA patients than for patients with iron deficiency anemia (F = 6.01, P < 0.025).     

Lower limb arterial incompressibility and obstruction in rheumatoid arthritis

BACKGROUND: Despite increased cardiovascular morbidity and mortality in rheumatoid arthritis, the peripheral arteries remain understudied. OBJECTIVE: To examine the lower limb arteries in age and sex matched, non-smoking subjects with and without rheumatoid arthritis. METHODS: The ankle-brachial index (ABI) was measured at the posterior tibial and dorsal pedal arteries. Arteries were classified as obstructed with ABI < or =0.9, normal with ABI >0.9 but < or =1.3, and incompressible with ABI >1.3. Multinomial logistic regression was used to estimate differences in ABI between patients and controls, adjusting for cardiovascular risk factors, rheumatoid arthritis manifestations, inflammation markers, and glucocorticoid dose. RESULTS: 234 patients with rheumatoid arthritis and 102 controls were studied. Among the rheumatoid patients, 66 of 931 arteries (7%) were incompressible and 30 (3%) were obstructed. Among the controls, three of 408 arteries (0.7%) were incompressible (p = 0.002) and four (1%) were obstructed (p = 0.06). At the person level, one or more abnormal arteries occurred among 45 rheumatoid patients (19%), v five controls (5%, p = 0.001). The greater frequency of arterial incompressibility and obstruction in rheumatoid arthritis was independent of age, sex, and cardiovascular risk factors. Adjustment for inflammation markers, joint damage, rheumatoid factor, and glucocorticoid use reduced rheumatoid arthritis v control differences. Most arterial impairments occurred in rheumatoid patients with 20 or more deformed joints. This subgroup had more incompressible (15%, p< or =0.001) and obstructed arteries (6%, p = 0.005) than the controls, independent of covariates. CONCLUSIONS: Peripheral arterial incompressibility and obstruction are increased in rheumatoid arthritis. Their propensity for patients with advanced joint damage suggests shared pathogenic mechanisms.     

Plasma levels and response to prednisolone therapy in rheumatoid arthritis

Clinical Rheumatology - Plasma prednisolone levels were measured in parallel with clinical and laboratory assessments in seven patients with rheumatoid arthritis on single daily doses of...     

HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments

OBJECTIVE—To determine the predictive value of shared epitope alleles for response to treatment in patients with rheumatoid arthritis.
METHODS—Patients from our previously published triple DMARD study were tested for the presence of shared epitope alleles (DRB1 *0401,0404/0408, 0405,0101, 1001,and 1402). Patients who were shared epitope positive were then compared with those who were negative to see if there was a differential effect on therapeutic response.
RESULTS—Shared epitope positive patients were much more likely to achieve a 50% response if treated with methotrexate-sulphasalazine-hydroxychloroquine compared with methotrexate alone (94% responders versus 32%, p<0.0001). In contrast shared epitope negative patients did equally well regardless of treatment (88% responders for methotrexate-sulphasalazine-hydroxychloroquine versus 83% for methotrexate). Additionally, a trend toward an inverse relation of the gene dose was seen for response to methotrexate treatment (p=0.05).
CONCLUSIONS—These data suggest that determining shared epitope status may provide clinical information useful in selecting among treatment options.

Keywords: DRB1; rheumatoid arthritis; combination treatment; shared epitope     

Lower extremity peripheral neuropathy and ischemic ulcers associated with giant cell arteritis

A patient with previously treated, temporal artery biopsy proven, giant cell arteritis (GCA) developed lower extremity ulcers and sensory neuropathy. Sural nerve biopsy showed epineural vessels with focal mild chronic inflammation. The lower extremity skin and nerve abnormalities improved after retreatment with prednisone. The rare manifestations of lower extremity skin and peripheral nervous system involvement associated with GCA are discussed. GCA must be considered in lower extremity ischemic processes of the skin and peripheral nervous system.