Robert G. Micheletti

Mönckeberg Sclerosis Revisited: A Clarification of the Histologic Definition of Mönckeberg Sclerosis

CONTEXT Medial calcification of muscular arteries is known as Mönckeberg sclerosis (MS). Although this was first described in 1903, disagreement persists over its precise histologic appearance. Some, including Mönckeberg, have written that the media alone are calcified, whereas others maintain that both the media and internal elastic lamina (IEL) are involved. Since vascular calcification is of great interest to investigators and clinicians, defined criteria for classifying calcified arterial lesions are important. OBJECTIVE To clarify the histologic definition of MS with regard to calcification of the IEL. DESIGN We reviewed slides from 14 incisional and excisional surgical biopsies and autopsy specimens containing arteries with previously diagnosed MS. We looked specifically for medial and IEL calcification and used von Kossa, alizarin red, and trichrome/elastic stains to confirm our findings. We also performed a literature search on the histologic appearance of MS. RESULTS Both medial and IEL calcification were present in all specimens. Medial calcification extended alongside calcified IEL. In focal regions, calcification appeared limited to the IEL, with minimal medial calcification. Occasionally, calcified nodules in the media appeared separated from the IEL yet were connected to it in other planes of section. Despite these variations in appearance, IEL involvement was universal. Of 25 journal articles and texts, 10 state that MS involves the IEL with calcification, whereas 15 state or suggest that it does not. CONCLUSIONS Our findings indicate MS involves both the IEL and media with calcification in spite of inconsistencies on this point in the medical literature.

Coronary atherosclerotic lesions in human immunodeficiency virus–infected patients: a histopathologic study

BACKGROUND Studies suggest human immunodeficiency virus-positive (HIV+) patients have an increased risk of coronary artery disease (CAD), yet little is known about the histopathology, severity, or distribution of lesions. METHODS The coronary arteries of 66 deceased AIDS patients and 19 HIV controls (age <55) were dissected and graded for percent luminal stenosis by intimal lesions, percent of intima involved with lipid, and extent of intimal calcification on a scale of 0 to 3. Medical histories, antiretroviral therapies, and CAD risk factors were reviewed. RESULTS HIV+ patients were older than controls (P=.06), and more were male (P=.02). Thirty-five percent of HIV+ patients had stenosis >or=75% of at least one artery. Compared to controls, HIV+ patients had three times greater odds of stenosis >or=75%, controlling for age and sex (one-sided P=.03). Older age and male sex were also risk factors (one-sided P<.001). HIV seropositivity was associated with increased plaque lipid content (one-sided P=.02) and calcification (one-sided P=.08). Duration of HIV infection, antiretroviral therapy, and immune status did not predict severe disease in multivariate analyses. Previously unreported patterns of dystrophic calcification were observed in HIV+ patients and older controls. CONCLUSIONS Young to middle-aged patients dying from advanced AIDS have atherosclerotic CAD that may result in luminal narrowing, heavy calcification, and high plaque lipid content. The pattern of disease, location of lesions, and plaque composition are typical of atherosclerosis in HIV-negative patients. No relationship between antiretroviral therapies and atherosclerosis was seen in this small study of heavily treated patients.

Calcification of the internal elastic lamina of coronary arteries

Two well-recognized patterns of calcification occur in large- and medium-sized arteries, intimal calcification associated with atherosclerosis and medial calcification described by Mönckeberg. Calcification limited to the internal elastic lamina is a third pattern of calcification not previously reported in coronary arteries. Here we describe 19 cases of coronary artery internal elastic lamina calcification. We serially sectioned and examined the coronary arteries of 66 patients with advanced AIDS and 27 HIV− controls with other chronic illnesses. We observed calcification of the internal elastic lamina in 10 HIV+ patients and 9 controls. HIV− patients with internal elastic lamina calcification were significantly older than HIV− patients without it (P=0.008) and HIV+ patients with it (P=0.006). Occasionally, calcification encroached on adjacent intimal or medial tissue with mild fibrosis. There was frequent disruption of the internal elastic lamina but no evidence of inflammation. Calcification was the dominant histologic feature in all cases. Von Kossa, Alizarin red, and trichrome/elastic stains confirmed these findings. Patients with internal elastic lamina calcification often had extensive medical histories but did not suffer from chronic renal failure or other conditions known to cause calcium dysregulation. We describe coronary internal elastic lamina calcification in HIV+ patients and older HIV− adults. The clinical significance of this finding is unknown. It could lead to arterial stiffening and increased pulse pressure and could be mistaken for intimal calcification on coronary imaging. Internal elastic lamina calcification may result from premature aging due to HIV disease and chronic illness or from metabolic disorders in HIV+ patients.

Role of Diet in Rheumatic Disease

Millions of people suffer from rheumatic diseases such as gout, fibromyalgia, osteoarthritis, and rheumatoid arthritis. These can be incapacitating and detrimental to quality of life. Diet, nutrition, and weight loss have shown promise in alleviating some of this disease burden. These lifestyle changes may give patients a feeling of control and ownership over their disease as well as a nonpharmacologic means of treatment. This article reviews the available research on the effects of diet and nutrition on rheumatoid disease.

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).

Small Vessel Vasculitis of the Skin

Small vessel vasculitis in the skin manifests with palpable purpura on the lower extremities. This clinical presentation prompts a complete physical examination, history, and review of systems, as well as biopsies for routine processing and direct immunofluorescence to confirm the diagnosis. The presence of vasculitis in other organs, associated underlying conditions, and the severity of cutaneous manifestations dictate management. The majority of cases are self-limited, and overall the prognosis is favorable. Still, a subset of patients can have serious complications and chronic or recurrent disease.

Atypical manifestations of graft-versus-host disease

BACKGROUND Cutaneous graft-versus-host disease (GVHD) is classically described as morbilliform when acute and lichen planus-like or sclerotic when chronic. In addition to these well-known clinical forms, there are many other presentations of GVHD that are important to recognize. As the number of patients undergoing stem cell transplantation increases and the survival after transplantation improves, the prevalence of GVHD is expected to rise, and its various presentations will be increasingly encountered in clinical practice. OBJECTIVE We sought to report unusual manifestations of skin GVHD and provide a summary of typical and atypical presentations of GVHD reported in the literature. METHODS Patients with stem cell transplantation who developed unusual eruptions after transplantation had biopsy specimens taken to evaluate for histopathologic evidence of GVHD. RESULTS Six patients presented with unusual cases of biopsy-proven GVHD, including follicular hyperkeratosis, thick-appearing white tongue, inverse pityriasis rosea-like, and eczema craquelé-like GVHD. LIMITATIONS This study is limited by case number. CONCLUSIONS Because of the high rate of cutaneous involvement with GVHD, the accessibility of the skin for diagnosis, and the morbidity associated with severe or long-standing skin involvement, it is important for dermatologists to recognize and accurately diagnose cutaneous GVHD in all its protean manifestations.

Hidradenitis suppurativa: current views on epidemiology, pathogenesis, and pathophysiology.

Hidradenitis suppurativa (HS) is a disease characterized by chronic follicular occlusion and secondary inflammation of the apocrine glands. The disease is uncommon but not rare. Further epidemiologic study is required to better determine HS prevalence in various populations. Women are affected three times more often than men, although HS tends to be more severe in men. The typical age of onset is in the second and third decades; HS is rare prior to puberty, and the prevalence is lower in older adults. A number of factors (particularly cigarette smoking) and comorbid conditions (especially obesity) are associated with HS, but causative relationships have not been established.

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.

SJS/TEN 2017: Building Multidisciplinary Networks to Drive Science and Translation

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening, immunologically mediated, and usually drug-induced disease with a high burden to individuals, their families, and society with an annual incidence of 1 to 5 per 1,000,000. To effect significant reduction in short- and long-term morbidity and mortality, and advance clinical care and research, coordination of multiple medical, surgical, behavioral, and basic scientific disciplines is required. On March 2, 2017, an investigator-driven meeting was held immediately before the American Academy of Dermatology Annual meeting for the central purpose of assembling, for the first time in the United States, clinicians and scientists from multiple disciplines involved in SJS/TEN clinical care and basic science research. As a product of this meeting, this article summarizes the current state of knowledge and expert opinion related to SJS/TEN covering a broad spectrum of topics including epidemiology and pharmacogenomic networks; clinical management and complications; special populations such as pediatrics, the elderly, and pregnant women; regulatory issues and the electronic health record; new agents that cause SJS/TEN; pharmacogenomics and immunopathogenesis; and the patient perspective. Goals include the maintenance of a durable and productive multidisciplinary network that will significantly further scientific progress and translation into prevention, early diagnosis, and management of SJS/TEN.