Calciphylaxis in a patient without renal failure or elevated parathyroid hormone: possible aetiological role of chemotherapy.

Calciphylaxis is a rare, often fatal disease characterized clinically by progressive cutaneous necrosis and ulceration, and histologically by vascular calcification and thrombosis. It has been described in association with end-stage renal disease, after initiation of dialysis, following renal transplantation, and in patients with hyperparathyroidism. We present the first case of calciphylaxis occurring in a patient with both normal renal function and parathyroid hormone level and discuss the possible aetiological role of chemotherapy-induced functional protein C and protein S deficiency.

Generalized lupus erythematosus profundus in a patient with genetic partial deficiency of C4.

Lupus erythematosus profundus (LEP) is an unusual variant of cutaneous lupus erythematosus (CLE)that is characterized by chronic, recurrent inflammation of the subcutaneous tissue leading to fibrosis. It is found in the settings of both discoid and systemic lupus erythematosus. Generalized forms are extremely rare. We present a case of generalized LEP associated with genetic partial C4-deficiency.

Neurology and the skin.

As knowledge of pathophysiology grows, so does the refinement of diagnoses. Sometimes increased knowledge permits consolidation and unification. Unfortunately, at our present level of understanding, it usually demands proliferation of diagnostic categories. As tedious as this diagnostic splintering may seem, such is the price currently exacted of both the investigator and the clinician who seek to optimise management. Increased diagnostic refinement often requires inquiry into matters outside the bounds of one's specialty. Most often we turn to the radiologist or to the laboratory to narrow the differential diagnosis generated from the history and neurological examination. As we have shown, a useful intermediate step is extension of the physical examination to organs such as the skin, which are not the traditional preserve of the neurologist. That any text could confer the sophistication required for expert dermatological diagnosis is an unrealistic expectation. However, we hope that this review will encourage careful examination of the skin, hair, and nails by the neurological practitioner, with consideration of referral to a dermatologist when greater expertise is required.

"Centripetal flagellate erythema": a cutaneous manifestation associated with dermatomyositis.

We describe 3 patients with dermatomyositis who presented with flagellate erythema. This cutaneous eruption is characterized by erythematous linear lesions on the trunk and proximal extremities. Histologic examination of this eruption in one of our cases revealed an interface dermatitis. Review of the literature and records of 183 patients with connective tissue diseases from our institution has shown that this peculiar eruption has been reported only in dermatomyositis. Because of the location of this eruption, we encourage the use of the term "centripetal flagellate erythema" to distinguish this entity from other linear eruptions seen in patients with connective tissue diseases.

Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry.

OBJECTIVES: The present study describes the demographics, mortality, morbidity and recurrence rates of autoimmune-associated congenital heart block (CHB) using information from the Research Registry for Neonatal Lupus. BACKGROUND: Isolated CHB detected at or before birth is strongly associated with maternal autoantibodies to 48-kD SSB/La, 52-kD SSA/Ro and 60-kD SSA/Ro ribonucleoproteins and is a permanent manifestation of the neonatal lupus syndromes (NLS). Available data are limited by the rarity of the disease. RESULTS: The cohort includes 105 mothers whose sera contain anti-SSA/Ro or anti-SSB/La antibodies, or both, and their 113 infants diagnosed with CHB between 1970 and 1997 (56 boys, 57 girls). Of 87 pregnancies in which sufficient medical records were available, bradyarrhythmia confirmed to be CHB was initially detected before 30 weeks of gestation in 71 (82%) (median time 23 weeks). There were no cases in which major congenital cardiac anatomic defects were considered causal for the development of CHB; in 14 there were minor abnormalities. Twenty-two (19%) of the 113 children died, 16 (73%) within 3 months after birth. Cumulative probability of 3-year survival was 79%. Sixty-seven (63%) of 107 live-born children required pacemakers: 35 within 9 days of life, 15 within 1 year, and 17 after 1 year. Forty-nine of the mothers had subsequent pregnancies: 8 (16%) had another infant with CHB and 3 (6%) had a child with an isolated rash consistent with NLS. CONCLUSIONS: Data from this large series substantiate that autoantibody-associated CHB is not coincident with major structural abnormalities, is most often identified in the late second trimester, carries a substantial mortality in the neonatal period and frequently requires pacing. The recurrence rate of CHB is at least two- to three-fold higher than the rate for a mother with anti-SSA/Ro-SSB/La antibodies who never had an affected child, supporting close echocardiographic monitoring in all subsequent pregnancies, with heightened surveillance between 18 and 24 weeks of gestation.

Serum CA-125 screening for ovarian cancer in patients with dermatomyositis.

Ovarian cancer is the most overrepresented malignancy diagnosed in women with dermatomyositis. Unfortunately, screening with pelvic examination rarely detects this cancer prior to the development of metastatic disease. Our objective was to examine the use of serum CA-125 antigen levels in screening patients with dermatomyositis for ovarian cancer. A single blinded, case-control study was conducted in our institution of CA-125 levels in 14 women diagnosed with dermatomyositis between 1986 and 1993, 4 of whom subsequently developed ovarian cancer. In the 4 patients who developed ovarian cancer ("cases"), CA-125 determinations were performed on serum stored 5 to 19 months prior to the diagnosis of ovarian cancer. In the remaining 10 patients ("controls"), serum was drawn for CA-125 level determination at the time of the study, and simultaneous gynecologic and endovaginal ultrasound examinations were performed to exclude clinical evidence of ovarian cancer. All CA-125 serum measurements were performed simultaneously by a technician blinded to disease status using one diagnostic kit. CA-125 was found to be elevated in 2 patients with ovarian cancer (on serum obtained 5 and 13 months prior to the date of diagnosis of ovarian cancer) and in none of the control patients without clinical or ultrasound evidence of ovarian cancer (relative risk = 20, 95% confidence interval = [0.64, 666]). In these 14 patients, the sensitivity of CA-125 elevation for detection of ovarian cancer was 50%, and specificity was 100%. Serum CA-125 screening for ovarian cancer in patients having dermatomyositis may be useful; however, prospective studies are needed to confirm this and to determine the effect of screening on cancer stage at diagnosis and long-term survival.

Anti-Ro(SS-A) antibody positive Sjögren's/lupus erythematosus overlap syndrome.

Unlike anti-Ro(SS-A) antibody positive subacute cutaneous lupus erythematosus (SCLE) patients, anti-Ro(SS-A) antibody positive lupus patients with Sjögren's syndrome (SS/LE) appear to have a more guarded prognosis. Our studies indicate these SS/LE patients have an increased frequency of pulmonary, neurological, and renal disease compared to SCLE patients.

Significance of the anti-Ro (SS-A) antibody in evaluation of patients with cutaneous manifestations of a connective tissue disease.

The anti-Ro(SS-A) antibody is arguably the most important antibody determination except for antinuclear antibodies in evaluation of patients suspected of having lupus erythematosus. During the past 25 years, studies have established the importance of this antibody in the evaluation of patients with atypical lupus erythematosus, who have a photosensitive dermatitis as the presenting sign. The purpose of this review is to demonstrate the utility and the necessity of this antibody determination in the evaluation of all patients with cutaneous manifestations who are suspected of having a connective tissue disease.

Dermatomyositis sine myositis: association with malignancy.

OBJECTIVE: To describe dermatomyositis (DM) sine myositis as a distinct diagnostic subclass of DM and the association with malignancy. METHODS: This case series includes all patients presenting to our primary and tertiary care outpatient dermatology department with DM and DM sine myositis between 1986 and 1993. Seven patients were diagnosed with classic DM and 12 with DM sine myositis. We analyzed average age of onset, duration of followup, clinical course, and incidence of associated malignancy in the patients with classic DM and DM sine myositis. RESULTS: No statistically significant differences were found in these 2 groups on examining age at onset and frequency of associated malignancy. Malignancy was diagnosed in 4 of 12 (25%) patients with DM sine myositis followed for a total of 50.8 patient-years (average followup 51 months) and in 2 of 7 (28%) patients with classic DM followed for a total of 20.6 patient-years (average followup 35 months). CONCLUSION: Although these patients with DM are select and few, they demonstrate that DM sine myositis may be quite similar to classic DM. It may be said that like DM, DM sine myositis may represent a paraneoplastic syndrome. DM sine myositis should be added to the currently accepted polymyositis/dermatomyositis classification system, with appropriate emphasis on the potential association with malignancy.

One hundred anti-Ro (SS-A) antibody positive patients: a 10-year follow-up.

To explore further the varied clinical expression of anti-Ro(SS-A) antibody positive patients and to determine the outcomes of these patients, we followed 100 anti-Ro(SS-A) antibody positive patients, originally seen at the Johns Hopkins Medical Institutions in 1982 and 1983, over a 10-year period. The results of this study indicate that anti-Ro(SS-A) antibody positive patients have a diverse clinical presentation and that the anti-Ro(SS-A) antibody response generally persists for years. Some of these patients appear to have a static disease process for years. However, 65% (51, including 13 deaths, of 78 patients) of the patients for whom we had follow-up data had a chronic (10 years or greater) progressive disease process. Black patients, in general, have an earlier onset of disease and may have a more severe disease than white patients. At least 25% of our anti-Ro(SS-A) antibody positive patients demonstrated a dynamic change in clinical presentation with the development of Sjögren syndrome and/or a progressive "rheumatoid-like" arthritis. Interstitial pulmonary disease, central nervous system disease, and vasculitic insults occur frequently in these patients. Renal disease occurred in 19 anti-Ro(SS-A) positive patients, and in 47% of these renal disease patients, no anti-DNA antibodies (dsDNA or ssDNA) were detected. Cutaneous manifestations are prominent in anti-Ro(SS-A) antibody positive patients with lupus. Photosensitivity and a malar dermatitis were the most common features. Twenty percent of lupus patients had discoid lesions, and 20% had SCLE lesions. Based on this study, we believe that anti-Ro(SS-A) antibody positive patients should be routinely evaluated for the emergence of systemic features. Since these systemic features are at least in part, if not solely, the result of inflammation, early treatment with steroids and/or immunosuppressive agents may minimize the damage and influence in a positive manner the significant morbidity and mortality observed in some anti-Ro(SS-A) antibody positive patients.

Ovarian cancer in patients with dermatomyositis.

A consensus regarding adequate screening to detect early malignancy in the setting of dermatomyositis (DMM) has yet to be reached. This issue is particularly relevant with regard to ovarian cancer, as early detection with routine examinations, ultrasound, and abdominal CT may not be successful. Four of 15 women diagnosed with and seen in our department for DMM between 1986 and 1993 were subsequently diagnosed with metastatic papillary serous ovarian carcinoma. One additional patient developed metastatic pelvic papillary adenocarcinoma, believed to be of ovarian origin. These diagnoses of advanced cancer were unexpected, as all women had undergone repeated cancer screenings beyond what is normally recommended for patients with DMM. The 5 women were strikingly similar in their initial presentations and subsequent courses. In each, the diagnosis of DMM was delayed from 2 to 10 months, as they were initially misdiagnosed with a photoinduced or contact dermatitis. All except 1 had severe, recalcitrant skin disease despite attempted therapy with antimalarial and immunosuppressive agents. All 4 patients who survived the postoperative period after tumor debulking showed either improvement or resolution of their DMM. It appears that women with DMM have an increased incidence of ovarian cancer, which is usually diagnosed months to a few years (range, 0 d to 6 y) after DMM has been diagnosed. Although recommendations have been made regarding cancer screening in these individuals, recommendations for initial and surveillance examinations vary from routine history and physical examination to evaluations including extensive radiologic evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal lupus erythematosus. Report of serological and immunogenetic studies in twins discordant for congenital heart block.

Autoantibody, HLA studies and C4 phenotypes were performed on twins discordant for isolated congenital heart block. Serum from the mother and cord blood from the infants revealed Ro(SSA) and La(SSB) antibodies in all three sera. No significant difference in Ro(SSA) antibody titre was noted in the cord blood of either twin when compared with maternal titres, as detected by a sensitive ELISA assay. The infants' mother was HLA-DR3 positive. Both infants had identical HLA and C4 phenotypes. Immunoblot analysis revealed that sera from both mother and infants reacted with the 52-kDa Ro(SSA) macromolecule. Quantitative cord blood IgM levels were not elevated in either twin. This study indicates that placental transfer of anti-Ro(SSA) or anti-La(SSB) alone to the fetus is not sufficient for the expression of congenital complete heart block. We conclude from this experiment of Nature that there must be a second event determining which infant develops complete heart block, but this is unknown at present.

Cutaneous manifestations of lupus erythematosus.

Lupus erythematosus is an autoimmune disease that demonstrates cutaneous, systemic, or both cutaneous and systemic manifestations. This article reviews the cutaneous manifestations of lupus erythematosus.

Anti-Ro(SS-A) HLA-DR3-positive women: the interrelationship between some ANA negative, SS, SCLE, and NLE mothers and SS/LE overlap female patients.

During the past 15 years, the clinical spectrum associated with the anti-Ro(SS-A) antibody response has been defined. Various clinical presentations, including subacute cutaneous lupus erythematosus, the neonatal lupus syndrome, the Sjögren's syndrome/lupus erythematous overlap syndrome, and primary Sjögren's syndrome, have been detected in association with the anti-Ro(SS-A) response. The anti-Ro(SS-A) antibody response is associated with the HLA-DR2 and HLA-DR3 phenotypes. There is now a good deal of evidence to suggest that many anti-Ro(SS-A)-positive HLA-DR3 women are genetically closely related, sharing in common an enriched frequency of the HLA-DR3-linked B8, DQw2, and DRW52 phenotypes. DNA sequence studies have confirmed this genetic relationship. These studies have led us to the following conclusions. 1) The HLA-DR2 and HLA-DR3 associations with systemic lupus erythematosus and the HLA-DR3 association with Sjögren's syndrome are related to the anti-Ro(SS-A) antibody response and not to the clinical disease expression. 2) HLA-DR3 anti Ro-positive female patients with first-degree Sjögren's syndrome, subacute cutaneous lupus erythematosus, or Sjögren's syndrome, or who are asymptomatic, are immunogenetically closely related even though the clinical presentations are strikingly different. All these HLA-DR3 anti-Ro(SS-A) antibody-positive women are at risk to give birth to a child with the neonatal lupus syndrome.

Cutaneous manifestations of Sjögren's syndrome.

The major mucous membrane and cutaneous manifestation of Sjögren's syndrome (SS) is xerosis. Severe dryness of the eyes, mouth, nasal passage, and vagina produce many annoying symptoms, including photophobia, burning and itching of the eyes, alterations in taste and smell, recurring nonallergic bacterial sinusitis rhinitis, and dysparunia. SS patients frequently complain of dryness of lips and soreness and a burning sensation of the tongue and oral mucosa. SS patients also complain of dryness of their hair and note a decrease in luster, and severe dryness of the skin is frequently accompanied by pruritus.