Michael M. Wolz

Human Herpesviruses 6, 7, and 8 From a Dermatologic Perspective

Human herpesviruses (HHVs) have frequently been suspected as etiologic agents or cofactors in cutaneous disease. However, clearly established associations are rare. Investigations into an etiologic association between HHVs and cutaneous disease are complicated by the ubiquity and nearly universal prevalence of some herpesviruses. This article summarizes the associations between cutaneous disease and HHV-6, HHV-7, and HHV-8. In addition to a personal library of references, the PubMed database of biomedical literature was searched using the following Medical Subject Heading terms: HHV-6, HHV-7, and HHV-8, each in conjunction with cutaneous manifestations, virology, epidemiology, dermatopathology, and therapeutics, between 1998 and March 2011. Free-text searches with known or suspected disease associations were added for broader coverage. The results have been summarized to provide a practical review for the physician likely to encounter cutaneous diseases.

Pemphigus vegetans variant of IgA pemphigus, a variant of IgA pemphigus and other autoimmune blistering disorders.

Abstract:Pyodermatitis-pyostomatitis vegetans (PPV) constitutes an inflammatory mucocutaneous dermatosis that is associated with inflammatory bowel disease. Clinically, PPV appears as pustules on mucosal surfaces and as vegetating exudative plaques on intertriginous surfaces. It is typically a clinical diagnosis supported by histological findings. Microscopic findings include epidermal hyperplasia, focal acantholysis, and a dense mixed inflammatory infiltrate with intraepithelial and subepithelial eosinophilic microabscesses. In the recent literature, immunofluorescence has been thought to be negative in PPV or, if positive, an aberrant finding. Herein, we report 2 cases of PPV associated with inflammatory bowel disease, which display intercellular IgA deposits. Although these cases may represent isolated epiphenomena, it is possible that the paucity of PPV cases with immunofluorescent studies hitherto has led to an oversight of an interesting association between intercellular IgA and PPV.

Clinicopathologic features of IgG/IgA pemphigus in comparison with classic (IgG) and IgA pemphigus.

The pemphigus group is characterized by the presence of circulating immunoglobulins against desmosomes. IgG/IgA pemphigus is defined by the presence of IgG and IgA cell surface deposits upon direct immunofluorescence (DIF) and/or circulating IgG and IgA autoantibodies upon indirect immunofluorescence. Previous reports of patients with IgG/IgA pemphigus are sparse. Whether IgG/IgA pemphigus is best classified as a subtype of IgG (classic) pemphigus or IgA pemphigus, or as a distinct entity, has yet to be determined.

Eosinophils in lichen sclerosus et atrophicus

The classic histopathologic features of lichen sclerosus et atrophicus (LS) include lymphoplasmacytic inflammation below a zone of dermal edema and sclerosis. The presence of eosinophils in LS has received little attention, but the finding of tissue eosinophils, particularly eosinophilic spongiosis in LS, has been suggested as a marker for the coexistence of autoimmune bullous disease or allergic contact dermatitis (or both). We sought to determine whether the histopathologic presence of dermal eosinophils or eosinophilic spongiosis (or both) in biopsies from patients with LS is associated with autoimmune bullous disease, autoimmune connective tissue disease or allergic contact dermatitis.

Reticulated acanthoma with sebaceous differentiation: another sebaceous neoplasm associated with Muir–Torre syndrome?

Reticulated acanthoma with sebaceous differentiation (RASD) represents a rare benign cutaneous epithelial neoplasm with sebaceous differentiation. There has been much speculation about the relationship between RASD and Muir–Torre syndrome (MTS). We report a 53 year‐old man who presented with RASD in addition to a prior history of sebaceous adenomas. Immunohistochemically, the tumour cells in the RASD and sebaceous adenomas showed a significantly reduced MSH6 protein expression, whereas there was no loss of MLH1, MSH2 and PMS2. This benign neoplasm, which can be mistaken for various other cutaneous lesions with sebaceous differentiation, deserves wider recognition for its possible association with MTS.

Phosphatase and tensin homologue status in sporadic and Cowden syndrome-associated trichilemmomas: evaluation of immunohistochemistry and fluorescence in situ hybridization

16 years. From the data collected (Table 1) we have patch tested 310 paediatric patients between January 2011 and September 2013. Of these 310, 13 (4 2%) were found to be allergic to MCI/MI. Recent publications suggest testing MI alone, as it produces a higher yield of positive reactions, highlighting the fact that MI in combination with MCI may not be adequate to detect all MI allergies. Since August 2013 we have been testing MI as a separate entity on our standard series in paediatrics, to see whether we are able to pick up a greater volume of patients who are allergic to MI that were not being picked up when tested for MCI/MI alone. We have patch tested 18 paediatric patients since August 2013 and have identified two patients positive to MI alone giving a percentage positivity of 11%. We felt that all positive reactions are universally relevant due to the widespread exposure to wet wipes and cosmetics. Table 1 illustrates that in the 0–5-year age group, four patients or 6% were found to be allergic to MI or MCI/MI. The 6–11-year group identified nine positives to MCI/MI, equating to 7% positivity. The older age group, 12–16-yearolds, identified two positives to MCI/MI, giving 2% positivity in that age group. We noticed that the positive allergic reactions were more intense and thus achieved crescendo at the 96-h point. No irritant reactions were seen. We hypothesized that the highest frequency of allergy would been seen in the 0–5-year age group due to the likelihood of increased wet wipe use in that cohort. Fewer patients are patch tested in the 0–5-year age range as it is not very well tolerated and is rarely warranted. However, as we have seen when patch testing to MI alone, our two positives to date are in the under 5 years age group. However, an important factor to note is that allergy develops over recurrent exposure and so may not develop until later on in childhood. We propose that testing to MI alone as well as MCI/MI in the paediatric population will help to identify more allergy. This in turn will aid better management of eczema. It is also likely to reflect that there is indeed an epidemic of allergy to MI in the paediatric population as seen in the adult population.

Language barriers: challenges to quality healthcare.

Language barriers pose significant challenges to providing effective and high-quality healthcare. Of 291.5 million Americans 5 years of age and over, 60.6 million people (21%) speak a language other than English at home. In the United States, federal and state laws provide a framework to ensure healthcare access for individuals unable to speak English. Many larger healthcare institutions have access to interpreter services, and the availability of professional translators has been associated with improvements in patient satisfaction, communication, and healthcare access. However, it is not only the availability of professional translators that helps ensure quality healthcare; it is also the individual healthcare provider’s cultural competence that is a cornerstone in reducing ethnic and racial disparities. An in-depth survey of 39 immigrant Somali women at a London obstetric center showed that the availability of translators alone is insufficient to overcome cultural barriers. Trust, accessibility, and quality of translation were other important factors. In addition to the logistical problem of providing adequate translation service, healthcare providers face individual ethical and epistemological predicaments in approaching patients with language barriers. These challenges can be divided into three main categories: space, time, and interpretation. Failure to recognize these challenges can lead to compromises in the quality of care. First, the presence of a translator can complicate the healthcare encounter as the interpreter may quite literally interpose between the healthcare provider and the patient. For example, if the interpreter stands between the healthcare provider and the patient, the latter two focus their attention on the interpreter rather than each other. This leads to the loss of important components of communication, including body language. In the most extreme of cases, the healthcare provider may even miss important clues to the diagnosis, such as constant lip-licking by the patient who presents for a perioral rash. Moreover, it leads to the loss of an opportunity of the healthcare provider and the patient to connect on a level beyond the spoken words, where smiles and warm gestures can establish trust and rapport. The physical presence of a translator leads to even more complexities when the translator is not a professional interpreter but a family member of the patient. In such scenarios, conflicts of interest and patient confidentiality come into play. Institutional guidelines often state that, whenever possible, translations should be performed by professional interpreters. In practice, professional translators are not always readily available, and the presence of bilingual family members can expedite and promote highquality healthcare. However, the principle of autonomy dictates that each patient should have a choice whether family members are present. Healthcare providers should also be open to alternative solutions the patient provides, such as mobile translators or other electronic devices. The patient and healthcare provider have a mutual interest and, as such, both may contribute to overcoming any language barrier. In many parts of the world, it is mandatory for healthcare providers to speak more than one language. Appropriate comfort with medical terms in different languages becomes a natural part of such a requirement. Ultimately, both the healthcare provider and patient should be comfortable with the translation services provided. Second, time is a critical factor in communication. The temporality of listening allows recourse to memory and interpretation in the listener. In the setting of healthcare, this often helps in reaching a diagnosis by recognizing patterns in the perceived communication. The words used by the patient may remind the healthcare provider of similar cases. However, it is not only the words used but also the time for interpretation that matter. Translation, even when real-time, stretches the time factor of communication and, thus, alters the healthcare provider’s usual method of working. For example, the healthcare provider might use the time necessary for translation to review the patient’s record or, more worryingly, pursue a different, unrelated task. The provider’s attention is therefore diverted from the communication with the patient. Similarly, the time needed to explain a diagnosis is also a time of interpretation of the patient’s reaction. Because of this interpretation, the healthcare provider can create an individualized management plan. If the patient’s reaction is

The philosopher in the clinic.

The unexamined life is not worth living. Socrates’ words have traditionally been used to promote the cause of philosophy. Accordingly, medicine without philosophy may not be worth practicing. Enormous resources are devoted to health and healthcare, but the goals of such expenditure are often vague. Similarly, the questions of what constitute health and healthcare, are often ignored in daily practice. In an age when medicine can be tailored to individual molecular variations, individual well-being enhanced by psychopharmacology, and genetic planning can influence embryonic morphology, the need to define the objectives of medicine is greater than ever. The medical practitioner should not blindly follow algorithms but rather should critically examine her daily work. Three considerations are crucial in such examination. First, medicine and the promotion of well-being are not equivalent. Second, pure science does not constitute medicine. Third, the starting point for the practice of medicine is not the disease but the relationship between the practitioner and the patient. Edmund Pelligrino wrote that ‘‘medicine cannot be successful until it knows exactly what it is trying to achieve, whether this achievement is possible, and whether it reflects a desirable goal of contemporary human culture’’. The questions of what constitutes health and its corollary, what constitutes disease, are existential. The concept of health has changed dramatically over history. What was once thought of as part of normal life is now considered a remediable health defect. However, the fact that modern medicine can fix something does not mean that it is broken. Health is a value-laden judgment, which does not depend solely on laboratory data. Values cannot be deduced from broken bones but must be derived from critical thinking. Put differently, what ‘‘ought to be’’ does not automatically follow from what ‘‘is’’. Similarly, what ‘‘should be done’’ does not follow from what ‘‘can be done’’. Thus, there must be an analysis of what society means when it refers to ‘‘health’’ or ‘‘disease’’. The results of such analysis are not for the ivory tower. They will translate into the optimization of scare resources and affect day-to-day clinical judgment. For example, if cancer were not thought to be a treatable disease, healthcare would be considerably cheaper, however poorer society might become for making such a judgment. In addition to understanding values and meanings, practitioners must understand the limits of knowledge. William James asserted that ordinary empiricism has a tendency to emphasize whirling particles at the expense of the bigger picture. Analogously, medicine has a tendency to emphasize drug composition and mortality ratios at the expense of causality and meaning. Even if a physician were to claim biological organisms are constituted by nothing but molecules and their interactions, the fact that most patients disagree with this claim already catapults the physician–patient interaction to the level of a relationship that cannot be defined in solely molecular terms. Thus, the practice of medicine does not only involve an understanding of objective data but also an understanding and appreciation of the patient’s point of view. The patient’s perspective crucially influences his condition and, thus, the applicability of generalized rules about the pathology is individually varied. Clinical judgment requires individualization, not only of individually organized biology but of individually understood biology. For example, every dermatologist knows that the same degree of acne can cause very different reactions in a teenager. Medicine cannot be equated with experimental science because a purely biological explanation of disease is insufficient to account for the patient’s experience of the disease and, therefore, insufficient, for the practice of medicine. Furthermore, the objectivity of science itself can be questioned. At the quantum level, the observer directly influences the experiment; observation defines outcome. Analogously, the interaction of physician and patient fundamentally influences the variables observed. Observation is shaped by the expectations of the observer. As the observed (patients) in medicine are not inert, it is even more likely that these expectations exert considerable influence. Essentially, there is no wholly neutral observation. Furthermore, the adoption of a particular theory (or diagnosis) influences the meaning of what is observed. For example, subscribing to an infectious etiology of an illness narrows the spectrum of investigations and hence diagnoses. Similarly, choosing the framework in which an observation is expressed shapes its results. As Wittgenstein persuasively argued, language itself is not neutral. In practice, how a physician phrases her patient’s 629

Ultrasound and Fine-Needle Aspiration in Dermatology, Underuse of Minimally Invasive, Efficient Diagnostic Tools

BACKGROUND Ultrasound imaging and ultrasound‐guided fine‐needle aspiration (FNA) are common procedures used to evaluate and sample cutaneous and subcutaneous tissue. Although ultrasound and FNA have been explored for individual neoplasms, lymph node involvement, and metastases, their use in day‐to‐day dermatology is not well defined. OBJECTIVE To investigate the use and utility of ultrasound and FNA in the dermatologic surgery division of a large academic institution. METHODS Retrospective case review of all ultrasound and FNA procedures ordered by a dermatologic surgeon over a 3‐year period. RESULTS Metastatic disease was suspected in 11 of 21 (52.4%) cases. Cytology confirmed the presence of metastatic disease in two of the 11 cases, and metastatic disease was identified in one additional case in which the diagnosis was not suspected at clinical presentation. Cytology revealed leukemia or lymphoma in three (14.3%) cases, two of which were new diagnoses. Sonographic imaging and cytology revealed a benign diagnosis in 16 (76.2%) cases, five of which were reactive lymph nodes. CONCLUSIONS The results suggest that ultrasound and FNA are underused techniques that may play an important role in dermatology diagnostics and have the potential for expansion in day‐to‐day clinical practice.

The unscheduled and incidental bystander: Legal, moral, and ethical considerations in the office

332 CASE SCENARIO 1 A 57-year-old woman presents for her annual skin examination. She is accompanied by her 61-yearold husband who the physician has not previously met. Both have an extensive history of intermittent high-intensity sun exposure. During the clinical encounter the physician cannot help but notice an irregular, hyperkeratotic, centrally ulcerated nodule on the bald scalp of the patient’s husband. The physician’s experience and clinical acumen lead her to suspect a squamous cell carcinoma.