Rafael Valenzuela

Paraneoplastic pemphigus: A report of three cases including one long-term survivor

BACKGROUND Paraneoplastic pemphigus is a newly described autoimmune disease characterized by painful mucosal ulcerations and polymorphous skin lesions in association with an underlying neoplasm. All reported patients with an associated malignant neoplasm have had a poor prognosis. OBJECTIVE We present three new cases of paraneoplastic pemphigus associated with a malignant neoplasm and further characterize this disease. METHODS We used clinical criteria, histologic and immunopathologic examinations, and immunophenotyping to characterize this disease. In addition, we performed immunoprecipitation studies with extracts of radiolabeled human keratinocytes to characterize the antigens to which patient serum binds. RESULTS All three patients had clinical, histologic, and immunopathologic findings that were strongly suggestive of paraneoplastic pemphigus. Their sera immunoprecipitated a complex of four polypeptides from human keratinocyte extracts with molecular weights of 250, 230, 210, and 190 kd, confirming the diagnosis of paraneoplastic pemphigus. The 250, 230, and 210 kd antigens comigrated with desmoplakin I, the 230 kd bullous pemphigoid antigen, and desmoplakin II, respectively. Lymphocyte immunophenotyping revealed large populations of monoclonal CD19+, CD5+ B cells in two cases. Although two of the patients died, one patient is alive and well 2 years after the diagnosis of paraneoplastic pemphigus. CONCLUSION We report three cases of paraneoplastic pemphigus. One patient is alive and well 2 years after diagnosis, which suggests that a subgroup of patients may have a more benign course.

Indirect immunofluorescence on rat bladder transitional epithelium: A test with high specificity for paraneoplastic pemphigus

BACKGROUND Paraneoplastic pemphigus is a blistering disease with specific serum immunoprecipitation findings. Although immunoprecipitation studies allow accurate diagnosis, they are time-consuming, expensive, and not readily available. In contrast, indirect immunofluorescence (IIF) testing of serum on transitional rat bladder epithelium is a simple and inexpensive method available to any immunopathology laboratory. OBJECTIVE Our purpose was to determine the specificity of positive IIF on rat bladder epithelium for paraneoplastic pemphigus. METHODS The IIF findings in four index cases of paraneoplastic pemphigus were compared with the findings in 47 patients with a variety of malignant neoplasms and no associated blistering disease as well as 49 patients with vesiculobullous or lichenoid disease but no neoplasia. RESULTS IIF was negative in all patients with neoplasia and no blistering disease and negative in all but one of the patients with vesiculobullous or lichenoid disease without neoplasia (98.9% specificity). CONCLUSION IIF on transitional rat bladder epithelium appears to be a highly specific test for paraneoplastic pemphigus. Because of its simplicity and inexpensiveness, we suggest that IIF be performed on transitional epithelium in any suspected case of paraneoplastic pemphigus.

Correlation between potency of calmodulin inhibitors and effects on cellular levels and cytotoxic activity of doxorubicin (adriamycin) in resistant P388 mouse leukemia cells.

The relationship between potency of phenothiazine and naphthalene-sulfonamide calmodulin inhibitors and their effects on cellular levels and cytotoxic activity of doxorubicin was evaluated using the doxorubicin-sensitive and greater than 100-fold doxorubicin-resistant P388 mouse leukemia model system. In cytotoxicity studies using cell counts based on proliferation following a 24-hr drug exposure and in survival based on colony formation in soft-agar after a 2-hr drug exposure, the calmodulin inhibitors significantly enhanced the cytotoxic effects of doxorubicin in the resistant but not parent-sensitive P388 cells. However, survival in soft-agar (based on colony formation) following long-term drug exposure (approximately 120 hr) revealed that the cytotoxic effects of doxorubicin were significantly increased by the calmodulin inhibitors in both sensitive and resistant P388 cells. Laser flow cytometry studies on single-cell doxorubicin levels indicated that treatment with doxorubicin in the presence of trifluoperazine had no effect on drug levels in sensitive cells but significantly enhanced cellular accumulation and retention of doxorubicin in resistant cells. Furthermore, unlike treatment with doxorubicin alone, in the presence of trifluoperazine, heterogeneity in cellular drug levels in the resistant P388 cells was not observed. Among the various calmodulin inhibitors effective in enhancing cellular levels and cytotoxic effects of doxorubicin in the resistant P388 cells, chlorpromazine was approximately two-fold less potent than trifluoperazine or prochlorperazine and only N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide but not N-(4-aminobutyl)-2-naphthalenesulfonamide was active.

Relapsing polychondritis: Immunomicroscopic findings in cartilage of ear biopsy specimens

Two cases of relapsing polychondritis are reported. Direct immunofluorescence examination of ear biopsy specimens in both patients showed the presence of granular deposits of immunoglobulins and the C3 component of complement at the chondrofibrous junction. These findings suggest that immunomicroscopic examination of ear cartilage could be diagnostically useful in this disease.

Lichen planus associated with neoplasia: A cell-mediated immune response to tumor antigens?

BACKGROUND Individual case reports have suggested an occasional association of lichen planus with internal malignancy. OBJECTIVE Our purpose was to describe five patients with a neoplastic disease in whom lichen planus developed. METHODS Serologic and immunopathologic studies were conducted. RESULTS No evidence of autoantibody production characteristic of paraneoplastic pemphigus was found, and antibodies reactive with basal cell keratinocytes were not detected. CONCLUSION Lichen planus may be rarely induced by neoplasia. A cell-mediated immune reaction possibly causes this phenomenon.

Chronic glomerular microangiopathy and metastatic carcinoma.

Two patients with metastatic colonic adenocarcinoma developed deterioration of renal function six and nine months after the diagnosis of malignant disease. A renal biopsy specimen in one case and both postmortem specimens revealed thickening of glomerular capillary loops with focal reduplication of basement membrane-like material. Ultrastructural examination of all three specimens demonstrated a lucent subendothelial zone and no evidence of electron dense deposits. Antifibrinogen staining outlined most capillary loops in one case. It appears that chronic intravascular coagulation induced by the neoplasm was the major pathogenetic process involved in the production of the glomerular lesion in each case.

Oral and cutaneous lichen planus pemphigoides

Lichen planus pemphigoides is a rare bullous disorder characterized by tense bullae on lichen planus lesions and on clinically uninvolved skin. A diagnosis of lichen planus pemphigoides is made on the basis of clinical, histologic, and immunopathologic evaluation. We describe a patient who had lichen planus pemphigoides of the skin and oral mucosa and briefly review the literature on this uncommon entity.

Relapsing polychondritis: A case diagnosed by direct immunofluorescence and coexisting with pseudocyst of the auricle

A case of relapsing polychondritis with perichondrial IgG and C3, dermoepidermal IgG, and a coexisting pseudocyst of the auricle is reported. The use of direct immunofluorescence testing in establishing a diagnosis of relapsing polychondritis and the expected findings are reviewed. In some cases direct immunofluorescence may allow a diagnosis of relapsing polychondritis before clinical criteria or a routine histologic evaluation suggests a definite diagnosis.

Comparison of alternative chromogens for renal immunohistochemistry

Renal immunomicroscopy using enzyme labeled reagents has been shown to be a reliable method for the identification of immunoglobulins and complement in the routine evaluation of glomerular disease. However, the potential carcinogenicity of benzidine derivatives used in the procedure represents a major disadvantage of the technique. With a series of 55 renal biopsy specimens evaluated by light microscopy, immunofluorescence, and electron microscopy from patients with a variety of renal diseases, a study was done comparing aminoethylcarbazole and the Hanker-Yates reagent (p-phenylenediamine and pyrocatechol), chromogens chemically unrelated to benzidine. Aminoethylcarbazole was not suitable for renal immunomicroscopy, since in cases of antiglomerular basement membrane disease the color reaction product was finely granular at high magnification. Specimens immunostained with the Hanker-Yates reagent yielded permanent water insoluble reaction products and immunomicroscopic patterns identical to the results observed with immunofluorescence in all cases. To our knowledge, no carcinogenic properties have been identified for p-phenylenediamine or pyrocatechol. The Hanker-Yates reagent may be used routinely for renal enzyme immunomicroscopic studies with no currently identified carcinogenic hazard to laboratory personnel.

Chronic hereditary nephritis:A clinicopathologic study of 23 new kindreds and review of the literature

Thirty-three patients with chronic hereditary nephritis, obtained from 23 unrelated families, were evaluated with respect to clinicopathologic features. Renal tissue was examined by light microscopy in 25 cases, immunofluorescence in 19 cases, and electron microscopy in 16 cases. The light microscopic findings varied, and foam cells were present in only four cases. Immunofluorescence was negative in all but four cases, and in these the immunomicroscopic pattern was compatible with the findings of end stage glomeruli and hyaline arteriolar sclerosis. Although electron microscopy uniformly showed marked thinning or splitting of the glomerular basement membrane, parallel splitting of the glomerular basement membrane with interposition of electron dense granular particles was seen in only eight cases. Association of glomerular basement membrane splitting with granular particles was observed in four of six patients with IgA nephropathy, in two patients with benign familial hematuria, and in a normal kidney donor. Eleven patients, seven men and four women, had chronic renal failure requiring dialysis. Of five patients who received renal allografts, three are alive, with post-transplant survival ranging from 24 to 70 months. The other two died of septicemia.