Magalys Vitiello

Cutaneous collagenous vasculopathy successfully treated with pulsed dye laser

An otherwise healthy 42-year-old woman presented to our service with a seven-year history of symmetrical telangiectatic lesions that initially appeared on her feet and then progressively spread to the lower extremities, abdomen, and arms. She was asymptomatic, without photosensitivity or bleeding lesions. Her family medical history was unremarkable for vascular diseases, and she denied the use of any medications. The physical examination revealed numerous punctuate, non-raised, reticulated, and reddish lesions that blanched with pressure, mostly located on her legs but also on her arms, abdomen, and lower neck (Fig. 1). The nails and mucosa were spared of lesions. Darier’s sign was negative. Complete blood count, complete metabolic panel, and coagulation tests were all normal. Antinuclear antibodies, anti-DNA, anti-Ro, and anti-La antibodies were negative. Chest x-ray, CAT scan, and venous Doppler were all normal. A skin biopsy taken from one of the leg lesions showed superficial ectatic blood vessels with thick walls within the papillary dermis and a perivascular eosinophilic amorphous material without inflammatory infiltrate or red blood cell extravasation. Epidermis and adnexal structures were normal (Fig. 2a,b). Immunohistochemical stain with CD34 antibody showed the endothelial basement located between normal endothelial cells and perivascular material. This material was emphasized by collagen type IV antibody stain, and it showed a concentric laminated distribution around the ectatic vessels (Fig. 2c,d). A diagnosis of cutaneous collagenous vasculopathy (CCV) was made. Laser therapy with 585 nm pulsed dye laser (PDL) at 8 J/cm of fluence, 2 ms, and 7 mm spot size was started first on the legs, and when some blanching was obtained with this treatment modality, it was then applied to the rest of the body (Fig. 3) once a month.

Ustekinumab for the treatment of nail psoriasis in heavily treated psoriatic patients

Psoriasis is a chronic, debilitating, T-cell-mediated inflammatory disease that affects the skin, nails, and joints, producing a negative impact on the patient’s quality of life. Nails are affected in up to 78% of psoriatic patients, resulting in pain, disfiguration, and poor cosmetic appearance. Psoriasis of the nail can occur without involvement of the skin or joints and may affect both the nail matrix and the nail bed, presenting with many features that can also be found in other inflammatory conditions. However, onycholysis with erythematous borders, irregular pitting, and salmon-colored patches are highly suggestive findings of psoriasis of the nail. Because most of the biggest trials and registries for psoriasis consider nail dystrophy a secondary change associated with plaque psoriasis and psoriatic arthritis, nail psoriasis does not count with standardized therapeutic regimens for its treatment. Although many effective therapies are available for psoriasis, unfortunately the same level of response is usually not seen for the nail involvement. Furthermore, validated quantitative assessment tools used to evaluate this response are still under constant review, and the resulting score might not reflect the true severity of the disease. Approval of ustekinumab for moderate to severe psoriasis represents a potential advance in the treatment for nail psoriasis. To our knowledge, there have not been reports in the literature of the use of this new drug for the treatment of nail psoriasis. We report our experience using ustekinumab for the treatment of psoriasis with nail involvement on 13 patients with moderate to severe psoriasis that tried multiple different therapeutic modalities in the past with poor results. 358

Utilización de solución de rapamicina tópica para el tratamiento de múltiples angiofibromas faciales en una paciente con esclerosis tuberosa

We report the case of a 27-year-old woman with a 10-year history of tuberous sclerosis. Her first visit to the dermatologist revealed several of the cutaneous manifestations characteristic of the disease, namely, disseminated facial angiofibromas (Fig. 1), multiple periungual Koenen tumors on both feet, hypopigmented macules on the trunk, and a shagreen plaque on the back. The patient also had epilepsy and mental retardation. She had no known internal hamartomatous lesions. A number of treatments----multiple shave excisions, pulsed-dye laser, electrodessication, and 0.1% topical tacrolimus ointment----had been applied in order to improve her facial appearance and reduce the number of angiofibromas. The response to treatment had been poor, with no appreciable reduction in the number of lesions and persistence of erythema. At that time, pharmacy-prepared topical rapamycin, 1 mg/mL, was applied twice daily on the affected areas of both cheeks. A clear clinical improvement was observed after 3 months’ treatment, with a reduction in the number of lesions and in the underlying erythema (Fig. 2). Tuberous sclerosis is an autosomal-dominant genodermatosis characterized by hamartomas affecting various organs, including the skin and central nervous system. Its pathogenesis is based on abnormalities of the proteins hamartin and tuberin, which are coded on the loci 9p34 and 16p13.3, respectively. Symptoms comprise the classic triad of multiple angiofibromas, epilepsy, and mental retardation, although this combination is only seen in 26% of patients. Despite its wide clinical variability and variable penetrance, facial angiofibromas are found in 83--90% of cases. These lesions are considered pathognomic and develop mainly on the nasolabial folds, cheeks, chin, scalp, forehead, and ears. They usually appear during the first decade of life, stabilize during adolescence, and are lifelong. They are not malignant, although their appearance constitutes a very frequent presenting complaint in these patients. Treatment can take several forms, including simple excision, cryosurgery, curettage, dermabrasion, carbon dioxide laser, and photodynamic therapy. No single treatment has proven sufficiently effective to control their onset or prevent recurrence.

Psoriasis treated with ustekinumab in a patient with hepatitis C

Miguel A. González-Gay, MD Department of Rheumatology Faculty of Medicine Marqués de Valdecilla University Hospital University of Cantabria Santander Spain References 1 Amano M, Grant A, Kerdel FA. A prospective open-label clinical trial of adalimumab for the treatment of hidradenitis suppurativa. Int J Dermatol 2010; 49: 950–955. 2 Moul DK, Korman NJ. Severe hidradenitis suppurativa treated with adalimumab. Arch Dermatol 2006; 142: 1110–1112. 3 Scheinfeld N. Treatment of coincident seronegative arthritis and hidradenitis suppurativa with adalimumab. J Am Acad Dermatol 2006; 55: 163–164. 4 Yamauchi P, Mau N. Hidradenitis suppurativa managed with adalimumab. J Drugs Dermatol 2009; 8: 181–183. 5 Blanco R, Martinez-Taboada VM, Villa I, et al. Longterm successful adalimumab therapy in severe hidradenitis suppurativa. Arch Dermatol 2009; 145: 580–584. 6 van der Zee HH, Boer J, Prens EP, Jemec GB. The effect of combined treatment with oral clindamycin and oral rifampicin in patients with hidradenitis suppurativa. Dermatology 2009; 219: 143–147. 7 Sartorius K, Lapins J, Jalal S, et al. Bacteremia in patients with hidradenitis suppurativa undergoing carbon dioxide laser surgery: detection and quantification of bacteria by lysis-filtration. Dermatology 2006; 213: 305–312. 8 Russ E, Castillo M. Lumbosacral epidural abscess due to hidradenitis suppurativa. AJR Am J Roentgenol 2002; 178: 770–771. 9 Dixon WG, Watson K, Lunt M, et al. Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving antitumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 2006; 54: 2368–2376.

Ustekinumab: when everything else fails?

Psoriasis is a chronic, debilitating, T-cell-mediated inflammatory disease that affects the skin and joints, producing a negative impact on the patient’s quality of life. One to three percent of the world’s population suffers from this condition in which the activated T helper-1 (Th1) lymphocytes play a pivotal role by releasing cytokines such as interferon gamma, tumor necrosis factor alpha (TNF-a), and interleukins (IL)-12 and 17. These cytokines are believed to be responsible for the characteristic keratinocyte and vascular changes of the disease. Recent findings also give IL-23, an effector of the Th17 pathway, an important role in the development of the disease because it elaborates other cytokines (IL-17A, IL-17F, IL-22 and IL-6) also linked to the production of the inflammatory response seen in psoriasis. Higher levels of these Th17 lineage cells have recently been associated with more severe disease as they are known to promote chemotaxis, activate the downstream inflammation, produce keratinocyte hyperproliferation, and cause acanthosis and hyperparakeratosis. IL-17, a very important cytokine produced by Th17 cells, activates a wide variety of cell types, including dendritic cells, macrophages, neutrophils, epithelial cells, and other T-cells implicated in multiple autoimmune and inflammatory diseases. This new evidence about the role of IL-23 in the pathogenesis of psoriasis suggests that blocking its activity may be useful for the treatment of this condition. Conventional psoriasis treatment includes topical modalities, phototherapy, and systemic therapy. These treatments target specific cells and cytokines to achieve remission and are used alone or in combination. A wider understanding of the disease pathogenesis, and the need for therapeutic alternatives that are convenient for the patient and that can provide long-term efficacy and safety, has led to the designing of new immunotherapeutic options (biologicals) that are more selective, have early response, and fewer side effects than the traditional systemic agents. Approval of ustekinumab (Stelara , Centocor Ortho Biotech Inc. Horsham, PA. USA), a fully human monoclonal antibody that binds to the p40 subunit shared by IL12 and IL-23 and targets both Th1 and Th17 pathways by preventing the interaction of these cytokines with their cell-surface interleukin-12Rb receptor, for moderate to 478

Erythema multiforme major associated with CMV infection in an immunocompetent patient.

Background: Cytomegalovirus (CMV) infection usually remains asymptomatic in immunocompetent adults, and few cases of complicated disease in nonimmunosuppressed patients have been reported. Erythema multiforme (EM), an acute and self-limiting skin eruption characterized by a typical targetoid lesion that may also affect the mucosa, is a hypersensitivity reaction that usually occurs after herpes simplex virus infection or use of certain drugs and resolves without complications in healthy individuals. To our knowledge, CMV infection has been associated with EM in only six patients. Objective: We present a case of an EM caused by CMV infection in a 35-year-old nonimmunosuppressed patient who was successfully treated with ganciclovir. Conclusion: Our report, like other similar reports found in the literature, suggests that CMV can trigger EM in apparently healthy individuals. Intravenous ganciclovir appears to be a good treatment option in these cases.

Exacerbation and change of psoriasis morphology in a patient treated with ustekinumab.

To the Editor: Ustekinumab is a newly developed human monoclonal antibody that binds to the shared p40 subunit of interleukins 12 and 23. It has shown efficacy in the treatment of chronic plaque psoriasis, with no remarkable short-term adverse events. Rapid worsening after drug discontinuation has been observed with other therapies for psoriasis, so dermatologists have experience managing these types of event. To our knowledge, this is the first report of this phenomenon in a patient treated with ustekinumab. A 53-year-old woman with an unremarkable medical history except for 12 years of chronic plaque psoriasis, which was biopsy confirmed, was referred to our office with a 10-day history of progressive worsening of her cutaneous disease. Previous treatments included acitretin, methotrexate, adalimumab, and etanercept. These treatments provided variable levels of improvement; however, complete clearance of the skin and/or long-term efficacy were never achieved with any of them. At the moment of this presentation, her chronic and recalcitrant plaque psoriasis was being treated with ustekinumab. She had begun treatment with this new drug 7 months previously, and three injections of 90 mg had been administered (day 0, month 1, and month 4). The dose was chosen according to her weight, which was 105 kg. Initially, the psoriatic plaques had improved after the first three injections. The patient was supposed to receive a new injection 3 weeks before being referred to our service; however, she did not once she started noticing ‘‘different-looking lesions’’ and worsening of her disease. On clinical examination, she presented marked erythroderma with disseminated pustules predominantly in the neck, trunk, palms, and soles (Figure 1). The patient was not taking any other medications, and no precipitating factors were identified. The patient was hospitalized and started on infliximab 5 mg/kg, showing improvement after the first infusion. Historically, the definition of rebound in the management of psoriasis has been controversial. For this purpose, the National Psoriasis Foundation Medical Advisory Board proposed to standardize the definition of this and other events in the recurrence of psoriasis. Rebound was defined as a Psoriasis Area and Severity Index (PASI) score of 125% of baseline or new generalized pustular, erythrodermic, or more inflammatory psoriasis ocurring within 12 weeks of stopping therapy. As is recognized by the authors, this term was designed for clinical study purposes and may not capture all cases that a physician would identify as a rebound. Moreover, the definition fails to recognize the biologic and clinical half-life of therapies, especially ustekinumab, which has a median half-life of around 21 days and is administered every 12 weeks. In our patient, the exacerbation of the cutaneous disease was noted at the time the patient was due to get her fourth injection. However, a change in morphology was detectable only 3 weeks after she should have received her indicated ustekinumab injection. Taking these into account, we consider our case a psoriasis flare with subsequent rebound. This may represent a continuum. In a phase III placebo-controlled clinical trial, 160 patients achieved a long-term response (PASI 75) when treated with ustekinumab 45 or 90 mg for 40 weeks; when it was withdrawn, psoriasis gradually recurred. The median time to loss of PASI 75 after withdrawal was close to 15 weeks, with no reports of rebound psoriasis. The maintenance of efficacy for more than 12 weeks may be related to the fact that the pharmacodynamic effects of DOI 10.2310/7750.2011.10114

Granulomatous slack skin-like clinical findings in Sézary syndrome

Granulomatous slack skin (GSS) is a very rare condition that has been described as a variant of mycosis fungoides. It is characterized by the development of bulky and pendulous skin folds in flexural areas that are histologically formed by atypical T lymphocytes, histiocytes and giant cells. We report the case of a 37‐year‐old African‐American female with history of Sézary syndrome (SS) that while on treatment for the disease and in a space of 1 month developed exorbitant slack folds in the axillae and cervical area mimicking GSS. The absence of giant cells and epithelioid granulomas in the biopsy ruled out this diagnosis. We report this peculiar SS presentation that clinically resembles GSS, but with histopathology that does not show the typical features of this condition. We also review the literature in regard to SS, GSS and granulomatous mycosis fungoides (GMF), particularly the existing criteria to differentiate these various entities.

Crioglobulinemia tipo I de desenlace fatal

Type I cryoglobulinemia, a condition associated with lymphoproliferative disorders, is caused by monoclonal immunoglobulins that precipitate at low temperatures. It mostly involves the skin and pathology study shows no signs of vasculitis. Management is usually based on immunosuppressive drugs associated with plasmapheresis for severe disease. The use of rituximab has recently been described for resistant cases. We present an unusual case of long-standing type I cryoglobulinemia associated with a monoclonal gammopathy of unknown significance. The patient developed extremely severe skin lesions with histological signs of vasculitis. The patient died due to the onset of noncutaneous manifestations of the cryoglobulinemia and complications of the immunosuppressive treatment.

Type I Cryoglobulinemia With a Fatal Outcome

KEYWORDS Cryoglobulinemia; Plasmapheresis; Sepsis Abstract Type I cryoglobulinemia, a condition associated with lymphoproliferative disorders, is caused by monoclonal immunoglobulins that precipitate at low temperatures. It mostly involves the skin and pathology study shows no signs of vasculitis. Management is usually based on immunosuppressive drugs associated with plasmapheresis for severe disease. The use of rituximab has recently been described for resistant cases. We present an unusual case of long-standing type I cryoglobulinemia associated with a monoclonal gammopathy of uncertain significance. The patient developed extremely severe skin lesions with histological signs of vasculitis. The patient died due to the onset of noncutaneous manifestations of the cryoglobulinemia and complications of the immunosuppressive treatment.