Julia S. Lehman

Folliculotropic Mycosis Fungoides: Single-Center Study and Systematic Review

OBJECTIVES To clarify clinicopathologic features and reconcile discrepancies in previous studies of folliculotropic mycosis fungoides (FMF). DESIGN A single-center retrospective clinicopathologic study and a systematic review of FMF. SETTING Tertiary referral center in the midwestern United States. PATIENTS Patients with clinical and histopathologic evidence of FMF seen at the tertiary referral center during a 12(1/2)-year period. MAIN OUTCOME MEASURES Clinicopathologic features of FMF. RESULTS Fifty patients (32 male [64%] and 18 female [36%]) met study criteria for the clinicopathologic review. Pruritic patches, plaques, and folliculocentric lesions (milia, cysts, and alopecia) on the head, neck, and trunk were common clinical findings. The mean time to diagnosis of FMF was 5.0 years. Diagnostic latency did not affect risk of death. One-year and 5-year overall survival rates were 96% and 62%, respectively. Frequent microscopic features were follicular mucinosis (74%) and epidermotropism (54%). Systematic review of 186 additional patients confirmed male predominance (ratio of men to women, 3.2:1.0), prevalent pruritus (73%), frequent follicular mucinosis (69%) and epidermotropism (37%) microscopically, and common head, neck, and trunk involvement. Combined data demonstrated that 6% of patients with FMF had concurrent non-mycosis fungoides hematologic malignant neoplasms and that the 5-year overall survival rate was 62% to 64%. CONCLUSION Folliculotropic mycosis fungoides has distinct clinical and microscopic features and is associated with a poor 5-year overall survival rate.

Role of primary prophylaxis for pneumocystis pneumonia in patients treated with systemic corticosteroids or other immunosuppressive agents for immune-mediated dermatologic conditions

BACKGROUND The incidence of pneumocystis pneumonia (PCP), an opportunistic infection caused by Pneumocystis jiroveci, in patients taking immunosuppressive medications for dermatologic indications is unknown. OBJECTIVE We sought to define the incidence of PCP in patients with dermatologic conditions, to characterize risk factors for PCP development in these patients, to examine PCP prophylaxis practices among dermatologists, and to document adverse effects of PCP prophylaxis medications. METHODS We reviewed the medical records of patients taking immunosuppressive medications for longer than 1 month who were treated for dermatologic conditions between 1998 and 2007 at Mayo Clinic, Rochester, MN. RESULTS Of 198 patients meeting inclusion criteria (150 [75.8%] of whom received no PCP prophylaxis), one patient (0.5% and 0.7%, respectively) had PCP that developed during the follow-up period. In this patient, a 94-year-old woman with bullous pemphigoid, severe interstitial pulmonary fibrosis, aortic stenosis, and hypoalbuminemia, PCP developed within 7 months of diagnosis and was treated with methotrexate and prednisone. She had not received PCP prophylaxis. Only 6 patients (3%) with dermatology as their primary service received PCP prophylaxis. Overall, rates of adverse effects with PCP prophylaxis were low. LIMITATIONS The study design was retrospective. Low rates of PCP precluded our development of concrete PCP prophylaxis guidelines. CONCLUSIONS Results did not support routine administration of PCP prophylaxis in all patients taking immunosuppressive medications. When prescribing immunosuppressive medications for dermatologic indications, physicians should consider PCP prophylaxis on a case-by-case basis.

Increased immunoglobulin (Ig) G4-positive plasma cell density and IgG4/IgG ratio are not specific for IgG4-related disease in the skin.

OBJECTIVES Immunoglobulin (Ig) G4-related disease (IgG4-RD), a fibroinflammatory condition that can affect multiple organs, is suggested by lymphoplasmacytic inflammation, fibrosis, phlebitis, and increased IgG4+ plasma cell (PC) tissue density. In patients with suspected IgG4-RD and skin changes, skin biopsy may serve as a diagnostic screen or to supplement nondiagnostic visceral biopsy specimens. We aimed to determine whether increased cutaneous IgG4+ PCs or IgG4/IgG ratio is specific for IgG4-RD. METHODS We examined 50 mucocutaneous specimens representing seven PC-rich dermatoses and reactive PC-rich infiltrates with IgG and IgG4 immunohistochemical stains. RESULTS IgG4+ density exceeded 10 cells per high-power field in 22 (44%) of 50 specimens, representing six of seven diagnoses and reactive infiltrates. In five specimens (10%), the IgG4/IgG ratio exceeded 0.40. CONCLUSIONS Moderately elevated IgG4+ PC density or IgG4/IgG ratio is a nonspecific finding in the skin. In cutaneous biopsy specimens showing increased IgG4+ PCs, careful consideration should be given to clinical, serologic, and other histopathologic features before attributing clinical changes to IgG4-RD.

Decreased Expression of Intercellular Adhesion Molecules in Acantholytic Squamous Cell Carcinoma Compared With Invasive Well-Differentiated Squamous Cell Carcinoma of the Skin

Intercellular adhesion proteins are poorly characterized in acantholytic squamous cell carcinoma (ASCC), a more aggressive tumor than nonacantholytic invasive well-differentiated squamous cell carcinoma (SCC) of the skin. In this study we compared expression of Dsg3, E-cadherin, and syndecan-1 in ASCC and SCC. Immunohistochemical detection of Dsg3, E-cadherin, and syndecan-1 in 22 ASCCs and 22 SCCs was graded on a semiquantitative scale for intensity of staining (SI) and degree of circumferential staining (CS) about the cell membrane. Results were assessed by means of conditional logistic regression and χ(2) analysis. Dsg3 and E-cadherin expression (SI, CS) was significantly decreased (P < .05) in ASCC compared with SCC, whereas staining for syndecan-1 was similar in the 2 tumor types. Differences in expression of adhesion markers between ASCC and SCC may contribute to the development of acantholysis in ASCC and its more aggressive biologic behavior.

Infection in autoimmune bullous diseases: A retrospective comparative study

Certain autoimmune bullous diseases (AIBD), including pemphigoid and pemphigus, confer increased infection risk. Infections have not been systematically studied in these conditions, however. Little is known about infection risk in these conditions, particularly dermatitis herpetiformis (DH). We aimed to characterize and compare infection patterns and risk factors in patients with pemphigoid, pemphigus, and DH. We retrospectively studied the medical records of Olmsted County, Minnesota, residents who had a diagnosis of AIBD between 1 January 1998 and 1 January 2011. Of 81 patients studied, 54 (67%) had pemphigoid, 11 (14%) had pemphigus and 16 (20%) had DH. Most patients studied developed at least one localized infection (72%) or one systemic infection (83%). Almost one‐third of patients (31%) developed infections requiring hospitalization or contributing to death. All patients taking systemic corticosteroids experienced a localized or systemic infection during the follow‐up period. Systemic infections were significantly less frequent in patients with DH than those with pemphigoid or pemphigus (P = 0.03), as were systemic infections requiring hospitalization or contributing to death (P = 0.002). Patients with DH were significantly less likely to require systemic corticosteroids (P < 0.001) and significantly more likely to receive dapsone (P = 0.002). The study design was retrospective and a limited number of patients met the inclusion criteria. Patients with AIBD frequently developed localized and systemic infections, a substantial portion of which contributed to hospitalization or death. Patients with DH experienced infections of lesser severity than patients with pemphigoid or pemphigus.

Smart teledermatopathology: a feasibility study of novel, high-value, portable, widely accessible and intuitive telepathology methods using handheld electronic devices.

To the Editor, Conventional telepathology may be achieved using one of three primary methods: (i) a storeand-forward method, which involves capturing static photomicrographs and transmitting them electronically from the microscope operator (‘sender’) to a personal computer operated by the interpreting pathologist (‘receiver’); (ii) a virtual slide system, which involves digitization of glass slides that are uploaded to a server accessible to the receiver, who can then virtually navigate the slides on a personal computer for interpretation and (iii) real-time telepathology, which enables the receiver to view streaming images on a personal computer simultaneously with the sender, who operates the microscope.1 High concordance between diagnostic interpretation using virtual microscopic images and that using tangible glass slides has been validated.1– 5 However, barriers to adaptation of virtual pathology include the required use of specialized, expensive hardware and proprietary software.2 Moreover, current telepathology methods are perceived as cumbersome, time-consuming to use and lacking in portability (authors’ personal observations). Traditional glass slides remain inexpensive to produce and stain, can be interpreted with relatively inexpensive and readily available equipment, and are very portable. We identified the need for a high-quality but low-cost, widely available, portable and intuitive telepathology methodology for use in a variety of clinical, research and educational settings. Such technology is needed to improve portability and ease of use. To address this unmet need, we developed novel telepathology methods that require only the use of a smartphone (i.e. cellular telephone equipped with a camera and internet connectivity), a commercially available microscope adapter, a standard professional microscope, an electronic tablet (i.e. computer tablet with internet connectivity and a high-resolution monitor) and a high-speed internet connection (together, referred to here as smart technology). We have termed this new methodology smart teledermatopathology and described and tested the feasibility of specific methods that closely simulate existing telepathology methods.

Kaposi varicelliform eruption in patients with Darier disease: a 20-year retrospective study.

BACKGROUND Kaposi varicelliform eruption (KVE), or herpes simplex virus (HSV) superinfection of pre-existing skin lesions, may complicate Darier disease. OBJECTIVE We sought to compare the clinical features and outcomes of patients with Darier disease who developed KVE superinfection with those who did not. METHODS A 20-year retrospective analysis of 79 patients with Darier disease treated at our institution was performed. RESULTS Eleven (14%) patients developed KVE, of whom 45% required hospitalization for their skin disease during the follow-up period. Patients with KVE had more severe Darier disease (P = .030) and were more likely to be hospitalized (P = .015). HSV was detected in erosions without concomitant vesicles or pustules in 64% of confirmed cases. In all, 23 (55%) patients with erosions had HSV testing pursued. LIMITATIONS Retrospective study design is a limitation. CONCLUSION The majority of KVE occurs in painless or painful erosions that may also appear impetiginized without vesicle or pustule formation. As HSV superinfection is correlated with severe Darier disease and risk for hospitalization, increased recognition of this phenomenon may lead to better patient outcomes.

Infection and infection prevention in patients treated with immunosuppressive medications for autoimmune bullous disorders.

Infection contributes to considerable morbidity and mortality in patients treated for autoimmune bullous disorders because of the impaired cutaneous barrier, alteration of the protective normal flora, and host immunosuppression (inherent and iatrogenic). Prevention of cutaneous impetiginization and infection starts with excellent wound care. In patients to be started on immunosuppressive medications, consideration should be given to vaccination status and possible need for pneumocystis pneumonia prevention. Patients should be educated on the signs and symptoms of early infection and the need to seek early medical intervention as needed.

Specific Causes of Death in Patients with Bullous Pemphigoid as Measured by Death Certificate Data: A Retrospective Cohort Study

Mortality rates in patients with bullous pemphigoid (BP) are higher than those in age‐matched counterparts. However, the specific causes of death in BP subjects have not been evaluated systematically.

Acquired lymphangiectasia (lymphangioma circumscriptum) of the vulva: Clinicopathologic study of 11 patients from a single institution and 67 from the literature.

Acquired lymphangiectasia of the vulva (ALV) is a rare condition thought to be secondary to pelvic lymphatic obstruction. Although benign, this entity often occurs after previous malignancy and can be confused with conditions such as genital warts. We sought to clarify the clinicopathologic features of ALV by studying affected patients from our institution and from the existing literature.