Robert H. Cook-Norris

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.

Pediatric erythromelalgia: a retrospective review of 32 cases evaluated at Mayo Clinic over a 37-year period.

BACKGROUND Erythromelalgia has not been well characterized in the pediatric population. OBJECTIVE We sought to review our experience of erythromelalgia in the pediatric age group. METHODS We conducted a retrospective review of patients 18 years of age and younger with a diagnosis of erythromelalgia who were examined at Mayo Clinic in Rochester, MN, from 1970 to 2007. RESULTS The records of 32 patients (girls, 22 [69%]) were evaluated. Mean age was 14.1 years (range, 5-18 years) and mean time to diagnosis was 5.2 years. Seven patients (22%) had a first-degree relative with erythromelalgia; 4 were from the same family. Physical activity was limited because of discomfort in 21 patients (66%) and school attendance was affected in 11 patients (34%). Noninvasive vascular studies, which compared temperature, laser Doppler flow, and transcutaneous oximetry in the toes, identified vascular abnormalities in 13 (93%) of 14 patients. Neurophysiologic studies with autonomic reflex screening (including quantitative sudomotor axon reflex test and thermoregulatory sweat testing) showed evidence of a small-fiber neuropathy involving the skin in 10 (59%) of 17 patients studied; there was no evidence of large-fiber neuropathy in 20 patients in whom electromyographic and nerve conduction studies were performed. Topical lidocaine was the most commonly prescribed treatment (44%). Fifteen patients were monitored for an average of 9.1 years (median, 5.0 years; range, 0.4-23.7 years). At last follow-up, 5 patients had stable disease, 4 showed improvement, two had resolution, one reported worsening of symptoms, and 3 had died (one suicide). LIMITATIONS Conclusions are limited because this was a retrospective chart review. CONCLUSION Erythromelalgia in pediatric patients is associated with substantial morbidity and even death. The majority of cases are not inherited. Most patients studied have associated small-fiber neuropathy. The disease course is variable. A reliable and safe treatment has not been determined.

Iatrogenic immunosuppression and cutaneous malignancy

Patients with autoimmune and inflammatory conditions often receive long-term immunosuppressive therapy. Some of the largest patient populations with iatrogenic immunosuppression include patients who have received solid-organ transplants or who have rheumatoid arthritis or psoriasis. Although treatments improve patient outcomes, individuals with immunosuppression subsequently may have an increased risk of skin cancer, including squamous cell carcinoma, basal cell carcinoma, and malignant melanoma.

Meyerson's naevus: a clinical and histopathological study of 11 cases.

We undertook a clinical and histopathological analysis of patients presenting with Meyersons naevi. Eleven patients with the characteristic histological features of a Meyersons naevus were identified over a 5‐year period. Diagnostic criteria included epidermal spongiosis and a dermal inflammatory infiltrate associated with a banal junctional or compound naevus. Cases were excluded if naevus cells showed moderate to severe atypia or regression. Patients were contacted by phone and interviewed regarding their lesions. The most common clinical appearance was a solitary, pruritic, erythematous eruption encircling a pre‐existing pigmented naevus. The trunk and proximal upper extremities were preferentially affected. Only one clinician listed Meyersons naevus in the clinical differential diagnosis. All cases demonstrated a pigmented junctional or compound naevus with epidermal spongiosis, parakeratosis and a perivascular lymphohistiocytic inflammatory infiltrate with scattered eosinophils. The inflammatory infiltrate consisted almost exclusively of CD3+ lymphocytes, the majority of which were CD4+. However, a substantial number were CD8+. In all patients, the lesions cleared with excision or spontaneously, without recurrence or progression to melanoma. The aetiology of this entity remains unclear and most clinicians are unlikely to be familiar with it.

Purely cutaneous Rosai‐Dorfman disease

Purely cutaneous Rosai-Dorfman disease Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is an uncommon benign proliferative disorder of histiocytes. Patients typically present with painless lymphadenopathy, fever, leukocytosis, elevated erythrocyte sedimentation rate, and hypergammaglobulinemia. 1 Extranodal sites are often involved (43% of cases) with the skin being the most common. 2 Purely cutaneous Rosai-Dorfman disease (CRD) without nodal or visceral involvement, although rare, has been documented. 3,4 We herein present an additional case and succinctly review the clinical and histologic features, differential diagnosis, and course. A 47-year-old African-American woman presented with a 7-month history of a slow growing, asymptomatic, purple plaque on her arm. Physical examination revealed a 5 × 2 cm violaceous plaque studded with multiple, soft, compressible, 6–8 mm nodules (Fig. 1). Lymphadenopathy and hepatosplenomegaly were not appreciated and her past medical history was otherwise unremarkable. A complete blood count, basic metabolic panel, and total serum protein levels were within normal limits, except for an increased erythrocyte sedimentation rate. Computed tomographic scans of the neck, chest, abdomen, and pelvis revealed no lymphadenopathy. The differential diagnosis based on physical examination included cutaneous lymphoma, histiocytoses, sarcoidosis, dermatofibrosarcoma protuberans, infectious processes, or other infiltrating neoplasms. Histopathologic examination showed a mildly acanthotic epidermis with a dense lobular infiltrate of mononuclear cells in the dermis. The infiltrate consisted of loosely packed, large histiocytes with ample foamy to granular eosinophilic cytoplasm, plasma cells, small mature lymphocytes, and occasional eosinophils. Several of the foamy histiocytes demonstrated engulfed plasma cells and lymphocytes (emperipolesis) (Fig. 2). The histiocytes were CD68, S-100, lysozyme, and alpha-1 antitrypsin positive and CD1a negative. Clinically, CRD commonly presents as a confluence of firm, indurated, papules or nodules with surrounding satellite lesions 2 . A xanthomatous or yellowish appearance may suggest aggregating histiocytosis. Histologically, the dermis contains a dense histiocytic infiltrate with background plasma cells and lymphocytes. 5 The large histiocytic cells show indistinct, “feathery” borders, eosinophilic cytoplasm, and prominent vesicular nuclei. 6 Engulfed plasma cells and lymphocytes (emperipolesis) are often seen. The proliferating histiocytes are S-100 positive, which is key, variably CD68 positive, and negative for CD1a. 5 The histologic differential diagnosis of other histiocytic disorders featuring emperipolesis includes malignant histiocytosis (histiocytic lymphoma), hemophagocytic syndrome associated with T-cell lymphoma, reticulohistiocytoma cutis and Langerhans cell histiocytosis. The lack of substantial mitotic activity and atypia help exclude malignant histiocytosis. In the hemophagocytic syndrome, the histiocytes are S100 negative. 7 The histiocytes in reticulohistiocytoma cutis can be S-100, making the distinction from CRD difficult. The histiocytes in this entity demonstrate a ground-glass appearance with a sharp cellular outline; concomitant plasma

Neutrophilic dermatosis of the hands: An underrecognized hematological condition that may result in unnecessary surgery

Neutrophilic dermatosis of the hands (NDH) is a recently described condition that resembles and, in fact, may represent a variant of Sweet syndrome confined to the hands [1]. NDH is characterized by erythematous, edematous plaques with a violaceous border occurring on the dorsal area of the hands. Vesicles, central necrosis, and ulceration can be prominent features. Associated clinical findings include pathergy, fever, and peripheral neutrophilia. Histopathology reveals a dense neutrophilic dermal infiltrate, often with subepidermal edema and occasionally leukocytoclastic vasculitis. A 57-year-old man sought consultation at an outside institution because of a 1-month history of progressive purplish discoloration of his left second digit (Image 1), with associated fever and malaise. Despite negative cultures, the affected digit was amputated because of concern about

The cutaneous manifestations of metastatic malignant melanoma

Cutaneous metastases are common sequelae of primary malignant melanoma. Because patients with melanoma are examined frequently after diagnosis, it is important that dermatologists are aware of the range of findings that may represent metastatic disease. Many case reports and a few retrospective series have been published detailing the wide variety of clinical presentations of cutaneous metastatic melanoma. This article reviews the various manifestations of metastatic melanoma of the skin and oral mucous membranes and summarizes treatment options for metastatic disease.

Painful erosions induced by patch testing in a patient with Hailey–Hailey disease

Editor, We present a 40-year-old woman with a history of biopsy-proven Hailey–Hailey disease. She had a remote history of irritation from adhesive tapes. She presented with pruritic, eczematous patches on her periocular skin and back that were suspicious for allergic contact dermatitis. Patch testing to our standard/preservative series and topical corticosteroid series was performed with paper tape because of her history of adhesive sensitivity. After 48 hours, the patient began to experience significant pain and irritation along her back in the area of the patches. The patches were removed, revealing extensive, urticariallike plaques and a few superficial erosions in areas beneath the paper tape, in addition to likely irritant reactions to lanolin alcohol and benzalkonium chloride (Fig. 1). Four days after placement, multiple erosions and scattered, fluid-filled vesicles were present (Fig. 2). A biopsy was offered to confirm our clinical impression of patch test-induced Hailey–Hailey disease, but the patient declined. Polymerase chain reaction (PCR) testing for herpes simplex virus (HSV) and varicella zoster virus (VZV) from a representative vesicle was negative. Bacterial culture revealed growth of Staphylococcus aureus sensitive to methicillin. The erosions improved with dilute acetic acid wet dressings over topical clobetasol cream applied twice daily for two weeks. There are several reports of allergic contact dermatitis occurring in patients with Hailey–Hailey disease. However, patch testing may be associated with complications in these patients, secondary to their inherent skin fragility. One group described a 43-year-old man with a known diagnosis of Hailey–Hailey disease who experienced a flare-up of disease secondary to infection with HSV type 1. Patch tests were applied to rule out a coexistent allergic contact dermatitis, and the patient subsequently developed severe blistering, which the authors attributed to a combination of sweating and frictional forces associated with patch testing. Another group reported two cases of Hailey–Hailey disease diagnosed when the patients developed severe, painful erosions after patch testing. A review of our database showed that we have patch tested over 5000 patients in the last 10 years, including several patients with Hailey–Hailey disease. This is the first case of patch test-induced exacerbation of Hailey– Hailey disease that we have encountered at our institution. Our case adds further evidence for the occurrence of this rare reaction in patients with Hailey–Hailey disease and indicates that patch testing must be performed with caution in these patients. In order to prevent this complication, some authors have recommended that patches should be removed at 24 hours rather than 48 hours in patients with Hailey–Hailey disease. We would add that, if patch testing is necessary, the least adherent tape possible should be applied to secure the patches, and the patient should be warned of this rare but potential reaction.

Scalp necrosis in giant cell arteritis after initiation of therapeutic corticosteroids

HCV load and aminotransferase levels in three out of four patients. The safety of CyA in the treatment of autoimmune disorders with concomitant HCV infection, even in patients with chronic active hepatitis, was confirmed in two different studies on 26 individuals, seven of whom had psoriatic arthritis. We can conclude that, according to Frankel et al, further investigations on the safety of CyA in the treatment of psoriasis in HCV-infected patients are advisable, but until this time, the available data indicate that CyA can contribute to a good outcome in patients affected by psoriasis and concomitant HCV infection in terms of both safety and efficacy.

Hydroxycarbamide‐induced dermopathy

Hydroxycarbamide (hydroxyurea) is an agent administered orally for the treatment of chronic myelogenous leukemia, myeloproliferative disorders, thalassemias, erythrocytosis, and sickle cell anemia [1–3]. An estimated 13% of patients with chronic myelogenous leukemia have mucocutaneous changes with long-term hydroxycarbamide therapy [4]. Myriad cutaneous adverse effects from long-term hydroxycarbamide therapy have been noted in the medical literature, including a dermatomyositis-like erythematous eruption on the hands, mucositis and oral ulceration, hair loss, nail pigmentation, and hyperpigmentation of the face [5]. The most common cutaneous adverse effect of long-term hydroxycarbamide therapy is painful lower-leg ulcers that typically appear spontaneously, involve the lateral malleoli and exhibit poor healing [6,7]. A 62-year-old woman presented with an 18-month history of a painful and pruritic eruption on the dorsum of her hands. The patient’s medical history showed myelodysplasia that had been treated with hydroxycarbamide for the past 5 years. Her hands showed shiny, violaceous papules over her knuckles and erythematous, reticulated, scaly plaques on her fingers and the dorsum of her hands (Image 1), mimicking Gottron papules and mechanic hands of dermatomyositis. Laboratory evaluation showed a negative result for antinuclear antibody and normal aldolase and creatine kinase values. A skin biopsy showed hyperkeratosis and epidermal atrophy. The basal layer showed vacuolar change and cytoid bodies. Direct immunofluorescence testing was negative for a lichenoid tissue reaction or lupus band. The skin eruption improved with use of a midpotency topical corticosteroid and discontinuation of hydroxycarbamide therapy. After 7 months of follow-up, only cutaneous atrophy remained. Unfortunately, the patient’s myelodysplasia had progressed to acute myelogenous leukemia. Several terms have been used to describe the cutaneous changes of the hands associated with long-term hydroxycarbamide therapy, including hydroxyurea dermopathy, pseudoImage 1. Shiny, violaceous papules over the knuckles and erythematous, reticulated, scaly plaques on the fingers and the dorsum of the hands caused by reaction to long-term hydroxycarbamide therapy.