Anti-C1q antibodies in systemic lupus erythematosus.

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

Drug-induced subacute cutaneous lupus erythematosus.

Subacute cutaneous lupus erythematosus (SCLE) is a subset of cutaneous lupus erythematosus with unique immunologic and clinical features. The first description dates back to 1985 when a series of five patients were found to have hydrochlorothiazide-induced SCLE. Since that time, at least 40 other drugs have been implicated in the induction of SCLE.

Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP180.

Lichen planus pemphigoides is an autoimmune subepidermal blistering disease. The finding of immunoglobulin G antibodies directed against the basement membrane zone differentiates it from bullous lichen planus. The aim of this study was to identify the target antigen of lichen planus pemphigoides autoantibodies. Sera from lichen planus pemphigoides patients (n = 4) stained the epidermal side of NaCl-split human skin in a pattern indistinguishable from that produced by bullous pemphigoid sera. In bullous pemphigoid, the autoimmune response is directed against BP180, a hemidesmosomal transmembrane collagenous glycoprotein. We previously demonstrated that bullous pemphigoid sera predominantly react with a set of four epitopes (MCW-0 through MCW-3) clustered within a 45 amino acid stretch of the major noncollagenous extracellular domain (NC16A) of BP180. By immunoblotting and enzyme-linked immunosorbent assay, lichen planus pemphigoides sera were also strongly reactive with recombinant bullous pemphigoid 180 NC16A. The lichen planus pemphigoides epitopes were further mapped using a series of overlapping recombinant segments of the NC16A domain. All lichen planus pemphigoides sera reacted with amino acids 46-59 of domain NC16A, a protein segment that was previously shown to be unreactive with bullous pemphigoid sera. Two lichen planus pemphigoides sera, in addition, reacted with the immunodominant antigenic region associated with bullous pemphigoid. In conclusion, there are now five bullous diseases that are associated with an autoimmune response to BP180: bullous pemphigoid; pemphigoid/herpes gestationis; cicatricial pemphigoid; linear immunoglobulin A disease; and lichen planus pemphigoides. In addition, we have identified a novel epitope within the BP180 NC16A domain, designated MCW-4, that appears to be uniquely recognized by sera from patients with lichen planus pemphigoides.

Pyoderma gangrenosum. A comparison of typical and atypical forms with an emphasis on time to remission. Case review of 86 patients from 2 institutions.

Pyoderma gangrenosum (PG) is an idiopathic, inflammatory, ulcerative disease of undetermined cause. The diagnosis is based on clinical and pathologic features and requires exclusion of conditions that produce ulcerations. An atypical bullous variant (atypical pyoderma gangrenosum, APG) exists with clinical features similar to those of Sweet syndrome. Because PG is a rare disease, few large case series have been reported. Pyoderma gangrenosum was first recognized as a unique disease entity in the first half of the 20th century. Cumulative knowledge of PG is based on a handful of case series and multiple individual case reports. To augment that knowledge, we present our experience with a large number of patients over a significant time. We performed a retrospective analysis of the medical records of 86 patients with PG who were evaluated and treated over 12 years at 2 university-based dermatology departments. The mean (+/- standard deviation) age of onset of PG and APG, respectively, was 44.6 +/- 19.7 years and 52.2 +/- 15.3 years. Lower extremity involvement was most common in PG, whereas upper extremity involvement was most common in APG. Associated relevant systemic diseases were seen in 50% of patients. Inflammatory bowel disease was the most common association in patients with PG, whereas hematologic disease or malignancy was most common in those with APG. Although a few patients were managed with local measures or nonimmunosuppressive treatment, the majority required oral corticosteroid therapy, often with systemic immunosuppressive treatment. PG patients required a mean 11.5 +/- 11.1 months of treatment to achieve remission compared with 9.0 +/- 13.7 months for patients with APG. Five patients (5.8%) had disease that was extremely refractory to multiple intensive therapies. The prognosis and disease associations for PG and APG appear to be different. Compared with PG, APG is more often associated with hematologic disease or malignancy, and remits more quickly.

A case of congenital multiple myofibromatosis developing in an infant.

BACKGROUND: Infantile myofibromatosis is marked by the development of firm, discrete, flesh-colored to purple nodules in skin, muscle, bone, and/or subcutaneous tissues. In cases without visceral involvement, the prognosis is excellent with expected spontaneous regression of nodules in 1 to 2 years. Visceral lesions are associated with significant morbidity and mortality generally within the first few months of life secondary to obstruction of a vital organ, failure to thrive, or infection. OBSERVATION: We present a case of congenital myofibromatosis initially presenting as a single, asymptomatic nodule on the midback of an otherwise healthy 1-month-old white boy. Over the subsequent 6 months, the child developed a left-sided head tilt with the formation of additional myofibromas of the skin and musculature, but without visceral involvement. Physical examinations have continued to show age-appropriate growth and development. CONCLUSION: Clinicians should be aware of this rare but potentially life-threatening entity and consider infantile myofibromatosis in the differential diagnosis of pediatric dermal and subcutaneous nodules, particularly when associated with a new onset of head tilt. Close clinical follow-up is recommended in all cases of infantile myofibromatosis.

Mucocutaneous changes in patients with lupus erythematosus. The relationship of these lesions to systemic disease.

The gamut of cutaneous lesions, as well as the spectrum of systemic disease, has been better characterized. In this section, the relationship of the skin lesion to systemic disease is discussed. Also, the importance of a careful characterization of the skin lesion is stressed. The therapy of cutaneous LE is also discussed.

Relationship of cancer to inflammatory muscle diseases. Dermatomyositis, polymyositis, and inclusion body myositis.

Dermatomyositis (DM) is probably associated with a greater frequency of malignancy than expected in the general population. For polymyositis (PM), there does not appear to be greatly increased risks. Ovarian cancer may be over-represented in women with DM. A paraneoplastic course occurs in some patients with DM, but is unusual. Even young patients with DM should be evaluated. The malignancy evaluation should be directed by symptoms, findings on physical examination or laboratory testing, or be age-appropriate.

Urticaria, angioedema, and rheumatologic disease.

Urticaria and angioedema are common processes that are experienced by 15% to 25% of the population at least once during a lifetime. This article presents an overview of urticaria and angioedema with emphasis on these processes as they relate to rheumatic disease. Discussion includes classification of urticaria and angioedema and recommended evaluation and treatment of patients presenting with such problems.

Cutaneous leukocytoclastic vasculitis. Clinical and laboratory features of 82 patients seen in private practice.

Eighty-two patients, with pathologically confirmed cutaneous leukocytoclastic vasculitis (LV), were seen in private dermatology offices. An analysis of the group was made to determine the relationship of cutaneous to systemic disease, the incidence and importance of laboratory abnormalities, and the prognosis of patients with cutaneous LV and to compare these results with previously published data derived from medical centers. Systemic disease occurred in 42 patients, but was transient and mild in most. Two patients died as a result of systemic vasculitis. The morphologic type of skin lesions most commonly found were palpable purpura (51 patients), urticarial-like lesions (17 patients), ulcers (eight patients), erythematous plaques (five patients), and/or nodules (five patients). Possible causative agents could be identified in 38 patients and included drugs (eight patients), infections (eight patients), or collagen vascular disease (17 patients). The course of the disorder was acute in 46 cases, chronic in 24, and recurrent in 12. The patients described herein fared better and had less significant systemic disease than those described in studies from medical centers. The data support the usual benign course of cutaneous LV as seen by practitioners despite frequent systemic symptoms or findings.

Chronic cutaneous lupus erythematosus. Clinical, laboratory, therapeutic, and prognostic examination of 62 patients.

Chronic discoid lupus erythematosus (DLE) is a common condition. Sixty-two patients with biopsy-proved, active DLE were observed and their conditions were analyzed for clinical, laboratory, and therapeutic data. Fifty-six patients had disease limited to the skin-26 localized and 30 widespread (above and below the neck). At the time of follow-up examination, active disease was present in 32 patients, 28 of whom had widespread DLE. Six patients had DLE as a manifestation of systemic LE (SLE). In four patients, the DLE preceded the development of SLE. Laboratory abnormalities were substantially more common in patients with widespread DLE than in patients with localized DLE. An analysis of therapeutic results in this series confirmed the beneficial effects of intralesional corticosteroids and antimalarial agents and demonstrated relatively poor responsiveness to topical or oral corticosteroids.

Sarcoidosis appearing initially as polymyositis.

Polymyositis is an idiopathic progressive muscle disease. Occasionally, sarcoidosis can be associated with a polymyositis-like picture, both clinically and on laboratory investigation. However, serial sections of muscle biopsies will usually demonstrate sarcoid granulomas. A case of sarcoidosis that began as polymyositis with diffuse interstitial pneumonitis is presented.

Keratoacanthoma. A clinical study.

Keratoacanthoma (KA) is a relatively common tumor believed to be a benign epidermal neoplasm. Ninety patients with one or more KAs were observed in regard to clinical, therapeutic, and prognostic implications. In particular, we were able to analyze the relationship of KA to internal malignant neoplasms in 78 patients. Keratoacanthoma is a disease of the elderly (mean patient age, 64.1 years). It is associated with other nonmelanoma cutaneous neoplasias in 21% of cases, a figure lower than that seen with squamous cell carcinomas. When solitary, KA is not associated with concurrent or subsequent internal malignant neoplasms more often than would be predicted by population statistics. Therapy is generally curative, but about 8% of the patients had recurrences. These patients may be successfully treated with several existing modalities.

Serum angiotensin I-converting enzyme level in patients with cutaneous sarcoidal granulomas.

In a previous study we found that only half of those patients presenting with cutaneous sarcoidal granulomas have evidence of systemic involvement. The current study was designed to determine whether abnormal angiotensin-converting enzyme (ACE) levels were predictive of multisystem disease. Serum ACE levels were determined in 15 patients with active cutaneous sarcoidal granulomas. The ACE levels were elevated in ten of the patients but did clearly differentiate those with systemic involvement. Three of the six patients with disease localized to the skin had elevated ACE levels, whereas seven of the nine patients with systemic disease had elevated ACE levels. The ACE levels did not correlate with the extent of cutaneous disease, or any individual or combined system involvement. A normal ACE level cannot be used to rule out a diagnosis of sarcoidosis and, conversely, an abnormal level does not confirm multisystem involvement.

Acute febrile neutrophilic dermatosis. Sweet's syndrome.

Acute febrile neutrophilic dermatosis (AFND) (Sweet's syndrome) is characterized by warm, erythematous plaques, accompanied by arthralgias, fever, and leukocytosis. A 53-year-old man was seen with chronic, recurrent, and unusually persistent AFND. The patient had a history of a gastrojejunostomy for peptic ulcer disease and had symptoms of the blind loop syndrome. Medical therapy for the blind loop syndrome failed to control his skin lesions, fever, or leukocytosis. His symptoms did respond to prednisone therapy, however. The relationship of AFND to the bowel bypass syndrome is discussed.

Cutaneous leukocytoclastic vasculitis with hyperglobulinemia and splenomegaly. A variant of hyperglobulinemic purpura of Waldenström.

Patient with hepatosplenomegaly and recurrent small purpuric lesions of cutaneous leukocytoclastic vasculitis was found to have a polyclonal elevation of gamma-globulin and a persistently elevated ESR. Circulating immune complexes were detected that support the concept of a postulated immune complex pathogenesis. Indomethacin therapy was ineffective, but prednisone therapy resulted in notable clinical improvement and the return of elevated immunoglobulin levels to the normal range. Patients with hyperglobulinemic purpura, which may be a subset of leukocytoclastic vasculitis, should be examined for associated conditions.

Bowen's and non-Bowen's squamous intraepidermal neoplasia of the skin. Relationship to internal malignancy.

The relationship of Bowen's disease to internal malignancy is controversial. We have studied 72 cases of Bowen's disease and compared them with 58 cases of non-Bowen's squamous intraepidermal neoplasia (SIN). Clinical data were obtained in all cases in an attempt to identify carcinogens and to detect the occurrence of other cutaneous or internal malignancies. Internal malignancy was not found more commonly in patients with Bowen's disease than in those with other forms of SIN. However, 5.7% of all patients win SIN were found to have a concurrent internal malignancy. Other cutaneous malignancies were also more frequent in these groups and may relate to sun exposure. Evidence for arsenic ingestion was not found in most patients. We believe that SIN either as Bowen's or non-Bowen's type may serve as an important marker for the presence of internal malignancy.

Isolated nodular cutaneous histoplasmosis. The initial manifestation of recurrent disseminated disease.

Cutaneous manifestations of histoplasmosis may be divided into primary and secondary lesions. Primary cutaneous histoplasmosis is rare; to our knowledge, there are only three reported cases in the literature. Secondary cutaneous histoplasmosis develops during the course of disseminated disease. An isolated nodule of the hand was the initially appearing sign of recurrent disseminated disease in our patient. Because of the extreme rarity of primary cutaneous histoplasmosis, cutaneous lesions that are proven to be due to histoplasmosis should alert the physician to the presence of disseminated disease.

Azathioprine. An effective, corticosteroid-sparing therapy for patients with recalcitrant cutaneous lupus erythematosus or with recalcitrant cutaneous leukocytoclastic vasculitis.

Azathioprine sodium has been reported to be effective therapy for chronic cutaneous lupus erythematosus (LE) but rarely for chronic cutaneous leukocytoclastic vasculitis (LV). We used azathioprine in the treatment of six patients with cutaneous LE, four of whom had subacute cutaneous (nonscarring) LE and two of whom had chronic cutaneous (scarring, discoid) LE, and six patients with chronic cutaneous LV. The conditions of all patients had been resistant to conventional therapy, and they required long-term oral corticosteroid therapy for control of their disease. Two of the patients with LE had prominent palmar and/or plantar involvement. Three patients with LE had an excellent response to azathioprine, with near complete clearing of the skin lesions, allowing a decrease in prednisone dosage. One patient with LE initially demonstrated significant improvement, but azathioprine therapy had to be discontinued because of pancreatitis. The treatment failed in two patients with LE; one had nausea and the other repeatedly developed a drug-induced fever. Five of the six patients with LV had improved conditions, with complete control of the disease occurring in two patients and partial control in three patients. Azathioprine is effective for some patients with cutaneous LE and chronic cutaneous LV, but it should be reserved for patients with severe disease in whom more conventional treatment fails.

Cutaneous sarcoidal granulomas and the development of systemic sarcoidosis.

Studies of patients with systemic sarcoidosis have indicated that those patients with cutaneous lesions have a poorer prognosis with a greater incidence of symptomatic pulmonary and ocular sarcoidosis. We examined 18 patients who had biopsy-proved cutaneous sarcoidosis for evidence of systemic involvement. Of the 13 patients who had no history of previously documented sarcoidosis, six had no evidence of systemic disease on history and physical examination, chest roentgenogram, pulmonary function testing, ocular examination, skin testing, and baseline laboratory testing. The seven remaining patients had evidence of sarcoidosis in another organ system, but six of the seven were essentially asymptomatic and required no therapy. The poorer prognosis associated with cutaneous sarcoidal granulomas drawn from populations with proved systemic sarcoidosis does not seem to apply to generally healthy outpatients with skin lesions as the initial manifestation of their disease.