Nicole Fett

Update on morphea: Part I. Epidemiology, clinical presentation, and pathogenesis

Morphea, also known as localized scleroderma, is a rare fibrosing disorder of the skin and underlying tissues. Morphea is differentiated from systemic sclerosis based on the absence of sclerodactyly, Raynaud phenomenon, and nailfold capillary changes. Patients with morphea commonly have systemic symptoms, such as malaise, fatigue, arthralgias, and myalgias, as well as positive autoantibody serologies. However, involvement of morphea is almost uniformly limited to those tissues derived from the mesoderm. The underlying pathogenesis of morphea is incompletely understood at this time, but ultimately results in an imbalance of collagen production and destruction.

Continuing medical educationUpdate on morphea: Part I. Epidemiology, clinical presentation, and pathogenesis

Morphea, also known as localized scleroderma, is a rare fibrosing disorder of the skin and underlying tissues. Morphea is differentiated from systemic sclerosis based on the absence of sclerodactyly, Raynaud phenomenon, and nailfold capillary changes. Patients with morphea commonly have systemic symptoms, such as malaise, fatigue, arthralgias, and myalgias, as well as positive autoantibody serologies. However, involvement of morphea is almost uniformly limited to those tissues derived from the mesoderm. The underlying pathogenesis of morphea is incompletely understood at this time, but ultimately results in an imbalance of collagen production and destruction.

Update on morphea: Part II. Outcome measures and treatment

Morphea is a rare fibrosing disorder of the skin and underlying tissues. The underlying pathogenesis of morphea is not completely understood at this time, but ultimately results in an imbalance of collagen production and destruction. Evidence-based treatment options of morphea are limited secondary to the rarity of the disease, and the lack of universally used validated outcome measures. The most commonly used outcome measures are skin scores, computerized surface area measurement, durometer, cutometer, thermography, and ultrasound measurements. The Localized Scleroderma Cutaneous Assessment Tool is a promising recently validated skin scoring tool that allows differentiation between activity and damage, is sensitive to change, and requires no additional equipment. The most robust data in the treatment of morphea exists for methotrexate in combination with systemic steroids and ultraviolet A1.

Adjuvant rituximab therapy of pemphigus: a single center experience with 31 patients

BACKGROUND We conducted a retrospective study of patients with pemphigus vulgaris (n = 24) and foliaceus (n = 7) treated with adjuvant rituximab to determine efficacy and adverse events. The end point for efficacy was complete remission of disease taking no or minimal therapy. OBSERVATIONS Eighteen patients (58%) achieved the study end point. Of these, 13 patients achieved complete remission off systemic therapy. Patients achieving the study end point had a median disease duration before rituximab therapy of 19 months vs 86 months in those not achieving the end point (P = .01). For the 18 patients achieving the end point, the median (SD) duration of remission was 19 (2) months. Eight of these 18 patients (44%) relapsed from 6 to 17 months after treatment. Serious adverse events attributed to rituximab treatment (osteomyelitis or phlegmon) occurred in 2 patients (6%). In paired serum samples from 10 patients before and after rituximab treatment, the percent change in serum desmoglein index value (median, -80%) was unrelated to the percent change in pneumococcal antibodies (median, +8%) (Spearman rank correlation coefficient r = -0.2). CONCLUSIONS Patients treated with rituximab earlier in the course of disease may have better outcomes. A discussion of rituximabs mechanism of action supports the rationale for early therapy. Prospective clinical studies are necessary to substantiate this observation.

Scleroderma: Nomenclature, etiology, pathogenesis, prognosis, and treatments: Facts and controversies

Scleroderma refers to a heterogeneous group of autoimmune fibrosing disorders. The nomenclature of scleroderma has changed dramatically in recent years, with morphea (localized scleroderma), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma encompassing the currently accepted disease subtypes. Major advances have been made in the molecular studies of morphea and systemic sclerosis; however, their etiologies and pathogenesis remain incompletely understood. Although morphea and systemic sclerosis demonstrate activation of similar inflammatory and fibrotic pathways, important differences in signaling pathways and gene signatures indicate they are likely biologically distinct processes. Morphea can cause significant morbidity but does not affect mortality, whereas systemic sclerosis has the highest disease-specific mortality of all autoimmune connective tissue diseases. Treatment recommendations for morphea and systemic sclerosis are based on limited data and largely expert opinions. Current collaborative efforts in morphea and systemic sclerosis research will hopefully lead to better understanding of the etiology and pathogenesis of these rare and varied diseases and improved treatment options.

Prevention and management of glucocorticoid-induced side effects: A comprehensive review

Systemic glucocorticoids are an essential therapy for a range of conditions, but their multiple side effects can produce significant morbidity for patients. The objective of this review is to discuss these side effects while addressing 3 questions: 1) What dose and duration of glucocorticoid therapy should prompt concern for individual side effects?; 2) How should clinicians counsel patients about these complications?; and 3) How can these problems be prevented or managed? To accomplish these objectives, we have created a series of tables and algorithms based on a review of relevant data to guide counseling, prophylaxis, and management of 11 glucocorticoid side effects. The first article in this 4-part continuing medical education series begins with a review of glucocorticoid pharmacology followed by a discussion of bone health (ie, osteoporosis and osteonecrosis).

Multicentric Reticulohistiocytosis with Dermatomyositis-Like Features: A More Common Disease Presentation than Previously Thought

Multicentric reticulohistiocytosis (MRH) is a rare form of non-Langerhans histiocytosis that presents with erosive arthritis and skin nodules. Approximately 25% of patients with MRH have an associated malignancy. Dermatomyositis is an inflammatory autoimmune condition that has also been associated with malignancy. To date, 7 cases of MRH have been reported to present with cutaneous features of dermatomyositis. We describe an eighth patient with MRH who presented with dermatomyositis-like features (V-neck erythema, shawl sign, Gottron’s papules and periungual erythema), who developed metastatic breast cancer 1 year after diagnosis. We hypothesized that clinical overlap between MRH and dermatomyositis was not as uncommon as review of the literature suggested. Careful review of the physical exam findings and photographs of the 234 papers reporting MRH revealed 27 cases of MRH with dermatomyositis-like features. Of these 27 cases, 7 (26%) were associated with a malignancy. Skin biopsies of the cutaneous features mimicking dermatomyositis revealed pathologic features of MRH. This is a descriptive analysis of published case reports. Based on a review of published case reports, MRH presenting with dermatomyositis-like features is likely fairly common. Histological examination of skin biopsies allows for disease differentiation. Differentiating MRH from dermatomyositis is important for management decisions and comorbidity screening.

Familial urticaria pigmentosa: report of a family and review of the role of KIT mutations.

Cutaneous mastocytosis is a rare clinically heterogeneous disorder characterized by mast cell infiltration. Mastocytosis affects both children and adults and has been reported to occur in families. Recent data suggest that mutations in the c-kit proto-oncogene are causative of mastocytosis not only in adults but in children and familial cases as well; however, mutation analysis other than D816V is not widely available, making detection of causative mutations problematic. We present the case of a 33-year-old man with a 30-year history of persistent urticaria pigmentosa and his 2 affected children. Sequencing of KIT exons 8, 10, 11, and 17 was carried out on a skin biopsy specimen and mucosal swabs of the incident case and was negative for known KIT mutations. Additional work-up was deferred by the family. Presentation of this familial case of urticaria pigmentosa demonstrates the complexity of genetic evaluation in clinical settings. It suggests that mutations other than those reported in exons 8, 10, 11, and 17 may also result in familial mastocytosis. Presentation of this case also allows for review of the mechanism of action of causative KIT mutations and the recent literature supporting KIT mutations in childhood and familial mastocytosis.

Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Ocular, cardiovascular, muscular, and psychiatric side effects and issues unique to pediatric patients.

The final article in this 4-part continuing medical education series reviews the ocular, cardiovascular, muscular, and psychiatric side effects of glucocorticoids and discusses side effects unique to pediatric patients.

Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Infectious complications and vaccination recommendations

Part 3 of this 4-part continuing medical education series reviews several important infectious complications of corticosteroid use, including a focus on pneumocystis pneumonia (PCP) prophylaxis, tuberculosis, viral hepatitis, and other infections, followed by a discussion of vaccination recommendations in immunosuppressed patients.