Faculty Bibliography

Fox-Fordyce disease (FFD) is a rare inflammatory disorder that affects the apocrine sweat glands. Clinically, lesions are equidistant, smooth, uniform, firm, folliculocentric papules, which can range in color from flesh-colored to red-brown to slightly yellow. Whereas the axillae are most commonly involved, FFD also can involve the anogenital and periareolar areas, lips, umbilicus, sternum, perineum, and upper medial aspects of the thighs. The underlying etiology of FFD remains unclear although epidemiologic data support a hormonal component because women are more commonly affected than men. Moreover, symptoms initially present after the onset of puberty, flare perimenstrually, and often resolve during pregnancy and after menopause. Histopathologic findings include the obstruction of the apocrine duct by a hyperkeratotic plug in the follicular infundibulum, which is believed to represent the primary pathophysiologic process; subsequent ductal rupture and resulting inflammatory response produce the typical clinical picture. Treatment of FFD is difficult because no one agent has proven particularly effective. Topical and interlesional glucocorticoids are often considered the first-line pharmacologic agents, although use is often limited by concerns for atrophy. Other agents that have shown some success include topical and systemic retinoids, topical clindamycin, topical pimecrolimus cream, benzoyl peroxide, and oral contraceptives. For medication-refractory cases, mechanical destruction or removal of the apocrine glands has been efficacious in small case series.

Morbihan disease, which consists of solid facial edema, is a rare complication of rosacea, a common cutaneous disorder in middle-aged individuals. The characteristic features of Morbihan disease are its chronic course, typical clinical picture, lack of specific laboratory and histopathologic findings, and refractoriness to therapeutic measures. Since its initial description in 1957, only a small number of cases have been reported in the dermatologic literature. We report a 54-year-old man who developed a two-year duration of erythema and edema that affects the upper and mid face, with accentuation in the periorbital region. Patch tests excluded an allergic contact dermatitis and histopathologic investigation showed small, nodular clusters of epithelioid cells in the dermis that were consistent with sarcoidal granulomata. A diagnosis of Morbihan disease was made owing to the combination of clinical and histopathologic findings. Therapeutic options for the disease remain unsatisfactory and treatments reported in the literature include systemic glucocorticoids, oral tetracyclines, thalidomide, isotretinoin, ketotifen, and clofazimine. Our patient failed a six-to-seven months course of minocycline prior to presentation and has since experienced improvement on gradually-increasing doses of isotretinoin.

Anetoderma is an elastolytic disorder that is associated with a number of infectious and autoimmune disorders. We present a case of a patient with generalized anetoderma, who was later found to have positive antinuclear antibodies and antiphospholipid antibodies (APAs). Numerous other cases have been reported in literature and some authors have suggested that anetoderma is a highly specific sign of APAs, with or without other manifestations of systemic lupus erythematosus or antiphospholipid syndrome [14]. Thus, work up for connective-tissue disorders should be considered in any patients who present with this skin finding.

We present a 56-year-old man with a two-year history of erythematous nodules and plaques on the forehead, frontal aspect of the scalp, and left side of the neck. Histopathologic findings are compatible with a diagnosis of diffuse large B-cell lymphoma (DLBCL). We present a brief review of primary cutaneous DLBCLs and address the putative association between DLBCLs and hepatitis C virus infection.

Minocycline has been used in the treatment of leprosy since the demonstration of its efficacy in inhibiting Mycobacterium leprae growth in 1987. Hyperpigmentation, a well-documented adverse effect, classically shows 3 clinical and histological patterns: type I consists of blue-black pigmentation in areas of current or previous inflammation, type II consists of blue-gray pigmentation of normal skin, often seen on the legs, and type III consists of diffuse muddy-brown pigmentation accentuated on sun-exposed sites. Whereas type I hyperpigmentation stains positively for hemosiderin and type III hyperpigmentation stains positively for melanin, type II hyperpigmentation stains positively for both. We describe 2 patients with leprosy on minocycline therapy who developed multiple patches of blue-gray pigmentation within preexisting leprosy lesions. Biopsies from both patients demonstrated deposition of brownish-black pigment granules within the cytoplasm of foamy histiocytes that was highlighted by both Perls and Fontana-Masson stains. Given the clinical and histological findings in our patients, it is as yet unclear whether this coexistent type I clinical pattern and type II histopathologic pattern of pigmentation is unique to multibacillary leprosy. These findings provide support for the existence of additional subtypes of minocycline-induced hyperpigmentation that do not adhere to the classic 3-type model described.

BACKGROUND: The longstanding concept of a Th1-Th2 dichotomy in leprosy, with Th1-predominant tuberculoid leprosy and Th2-predominant lepromatous leprosy (LL), has recently been challenged, and Cbl-b overexpression may emerge as an important factor in anergy and progression of LL. Moreover, Th17 and Th22 subsets have been identified as Th1-Th2 modulators in inflammatory skin diseases, most notably psoriasis, but their roles in leprosy have not yet been elucidated. The occurrence of pseudoepitheliomatous hyperplasia (PEH) with transepidermal elimination of mycobacteria in LL patients, which could theoretically be a portal for contact transmission, thus raises important immunological questions: Do Th17 and/or Th22 subsets mediate epidermal proliferation akin to Th1-driven psoriasis in supposedly Th2-predominant LL disease, and is the Th1-Th2 immunostat set systemically or locally? Furthermore, which microRNAs (miRs), signal transducers, and activators of transcription (STAT) proteins regulate this transition in leprosy, if any, and does differential Cb1-b expression play a role? OBSERVATION: A 71-year-old man presented with an infiltrative dermopathy characteristic of LL, as well as several hyperkeratotic plaques. Microscopic examination of the hyperkeratotic lesions demonstrated PEH with loss of the grenz zone and transepidermal elimination of acid-fast bacilli, whereas classic histopathologic features of LL were present at other sites. HYPOTHESES: We hypothesize that: Th17 and Th22 T-cell subsets act locally to induce T-cell plasticity in LL lesions, manifesting PEH; miR-181a is normal or increased in LL lesions with PEH compared to its expressional loss in classic LL lesions; miR-21 and STAT3 are increased in LL lesions with PEH, given their association with epithelial hyperproliferation; and Cbl-b is diminished in LL lesions with PEH compared to classic LL lesions. CONCLUSION: By understanding the factors that regulate T-cell and cytokine responses in leprosy, it should be possible to recognize these dynamic immunologic processes clinically and histopathologically and devise specific immunologic interventions.

The ideal dermal filler should offer long-lasting aesthetic improvement with a minimal side-effect profile. It should be biocompatible and stable within the injection site, with the risk of only transient undesirable effects from injection alone. However, all dermal fillers can induce serious and potentially long-lasting adverse effects. In Part II of this paper, we review the most common adverse effects related to dermal filler use.

Demonstration of T-cell receptor gene monoclonality often plays an important role in the diagnosis of T-cell lymphoma. When a test to detect monoclonality is performed on whole tissue sections, the presence of a reactive lymphocyte population may reduce sensitivity. This may be especially true for early or borderline cases of lymphoma. Microdissection techniques may be utilized to more readily identify a clonal population of lymphocytes. Subcutaneous panniculitis-like T-cell lymphoma represents a cutaneous lymphoid neoplasm whose clinical course may vary from an indolent, waxing and waning course to an aggressive course resulting in death. We report the first case of a microdissection technique used to facilitate diagnosing a case of subcutaneous panniculitis-like T-cell lympoma.

We report two unique cases of dermatofibrosarcoma protuberans (DFSP) that included a pseudocystic component. Molecular analysis of one of the cases showed a characteristic COL1A1-PDGFB rearrangement in both the main tumor and also in the cells lining the pseudocystic portion of the tumor, confirming the diagnosis and indicating that the lining represented a component of the proliferation. It is important to raise awareness of this rare variant within the varied spectrum of DFSP. Shvartsbeyn M, Lazar AJF, Lopez-Terrada D, Meehan SA. Pseudocystic dermatofibrosarcoma protuberans: report of two cases and demonstration of COL1A1-PDGFB rearrangement.

OBJECTIVE: Membrane endothelial protein C receptor (mEPCR) is highly expressed in peritubular capillaries of kidneys from patients with active and poorly responsive lupus nephritis (LN). We investigated the hypothesis that changes in the microvasculature are widespread with extension to the dermal vasculature. METHODS: Skin biopsies from uninvolved skin (buttocks) were performed in 27 patients with LN and 5 healthy controls. Sections were stained with specific antibodies reactive with mEPCR, adiponectin, intercellular adhesion molecule-1 (ICAM-1), and CD31; then assessed by enumeration of stained blood vessels (percentage positive blood vessels) blinded to knowledge of clinical information. RESULTS: There was a significant increase in the prevalence of blood vessels that stained for mEPCR and ICAM-1 in patients compared to controls [94% vs 59% (p = 0.045) and 81% vs 67% (p = 0.037), respectively]. Adiponectin staining and CD31 staining were similar between the groups (45% vs 43% and 98% vs 92%). Dermal staining for mEPCR was greater in patients with proliferative glomerulonephritis than in those with membranous disease (96% vs 60%; p = 0.029). A composite of poor prognostic renal markers and death was significantly associated with greater expression of mEPCR staining. CONCLUSION: These data are consistent with the notion that in patients with LN, activation of the microvasculature extends beyond the clinically targeted organ. The insidious expression of this widespread vasculopathy may be a contributor to longterm comorbidities.