Cutaneous side effects in a cohort of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: General description and further characterization, correlation with photoexposition and study of hypopigmentation as treatment's prognostic factor.

Cutaneous adverse effects (AE) related to tyrosine-kinase inhibitor (TKI) drugs have been mainly described as case reports. We have characterized their appearance and correlation with patient's photoexposition habits and, further, with treatment response, in 61 patients with chronic myelogenous leukemia (CML) treated with TKI drugs. We have found hypopigmentation in 49.2% of the cases and a statistically significant association with interferon (IFN) intake. Eyelid edema's frequency was 45.4%. Mean photo-exposure was 1.95 h/day and only 8.3% of the patients used sunscreen daily. 44.3% of the patients reported a lighter skin color with the treatment and a statistically significant relationship with conjunctival hemorrhage was also found. Concordance between patients and dermatologist was moderate (kappa index 0.41). We found xerosis (21.3%), eczematous eruptions (21.3%), melasma (4.9%) and other isolated skin problems (ie, granulomatous panniculitis) in up to 16.4% of cases. Appearance of hypopigmented macules is associated to vascular conjunctival fragility and these patients need a slightly longer time to reach a complete molecular response, but without additional changes in survival or relapse frequency. We have stablished a specific dermatologic diagnosis in all the cases and we have not found the previously published as maculopapular rashes. Hypopigmentation, the more frequent AE, was not perceived as a relevant side effect. Photosensitivity, in our cases, was not reported, although imatinib-treated patients avoided sun-exposure. In addition, we identified some nonpreviously described dermatologic conditions in patients taking TKI drugs, like granulomatous panniculitis tufted folliculitis or oral spindle cell lipoma.

Specific skin infiltration as first sign of localized stage Hodgkin's lymphoma involving an epitrochlear node.

Cutaneous manifestation as the first sign of Hodgkin lymphoma (HL) is very rare and diagnostically challenging; especially, because the clinical presentation of specific skin involvement by HL is polymorphous. We present a 44-year-old man with erythematous indurate papules and plaques in the right forearm and arm where skin biopsy showed an HL. He also has an enlarged epitrochlear node, and later histopathologic study confirmed the diagnosis of HL subtype-mixed cellularity. Immunohistochemical stains in both biopsies showed that the atypical cells were positive for CD30 and CD15, and negative for CD20 and CD3. PAX5 stained the nuclei of the atypical large lymphoid cells weakly and Oct-2 staining was negative in the atypical cells. EBER and LMP1 protein were negative in both biopsies. Epitrochlear involvement in HL, like in our case, is a rare event (<1%). We reviewed data about prognosis, clinical appearance, and treatment of all the cases of HL specific skin involvement published after Sioutos et al, emphasizing the cases where HL specific skin involvement was the first sign of the disease as in our patient.

Hypopigmented macules secondary to imatinib for the treatment of chronic myeloid leukemia: a histopathologic and immunohistochemical study.

BACKGROUND: A few series addressing the cutaneous side effects related to imatinib in the skin have been published, but only one described scarce histopathologic information in seven patients. OBJECTIVE: To characterize these lesions and compare the number of melanocytes between hypopigmented lesions and normal appearing skin. METHODS: We retrieved clinical data of the patients and performed 24 skin biopsies (13 from hypopigmented skin and 11 from normal-appearing skin) within a cohort of 41 patients with chronic myeloid leukemia treated with imatinib. We classified the biopsies into three patterns. RESULTS: About 45% of patients presented with periocular hypopigmentation. Perifollicular fibrosis was observed in hypopigmented skin biopsies (76.9%) and in normal-appearing skin (45.5%). Epidermal melanin, as determined with Masson-Fontana staining, and melanocyte number, as evaluated with MiTF, Melan A and c-kit immunostains, were lower in hypopigmented skin. CONCLUSIONS: Histopathologic study of hypopigmented macules demonstrates the presence of melanin with a statistically significant decrease in the number of melanocytes. Therefore, these findings differ from vitiligo, as melanocytes are present. Three histopathological patterns may be found, namely (a) perifollicular fibrosis, (b) lichen planopilaris-like and (c) apparently normal skin. One of the most striking histopathologic finding consisted of the presence of perifollicular fibrosis in both hypopigmented lesions and apparently normal skin.

Perforating folliculitis in a patient treated with nilotinib: a further evidence of C-kit involvement.

We present a case of perforating folliculitis in a patient treated with nilotinib, a kinase inhibitor. A 48-year-old man presented with a severely pruritic follicular rash for several months that started after reaching a complete molecular response of his myeloid chronic while treated with nilotinib. Clinical examination showed predominantly follicular pinpoint papules on trunk and proximal extremities and a biopsy showed a slightly dilated hair follicle with a focal disruption of the infundibular follicular epithelium. Other diseases related with perforating folliculitis were ruled out. The temporary relationship between the treatment and the appearance of the lesions suggests some pathogenic role of nilotinib. Relationship with nilotinib is also supported by previous similar cases related with sorafenib therapy. Both drugs inhibit c-kit and PDGF-R. PDGF-R has been previously involved in murine and human in vitro models of hair follicle cycle. So, our case supports in vivo the previous evidence of the importance of PDGF-R, a kinase, in the normal hair follicle development.

Psoriasis in humans is associated with down-regulation of galectins in dendritic cells.

We have investigated the expression and role of galectin-1 and other galectins in psoriasis and in the Th1/Th17 effector and dendritic cell responses associated with this chronic inflammatory skin condition. To determine differences between psoriasis patients and healthy donors, expression of galectins was analysed by RT-PCR in skin samples and on epidermal and peripheral blood dendritic cells by immunofluorescence and flow cytometry. In the skin of healthy donors, galectin-1, -3 and -9 were expressed in a high proportion of Langerhans cells. Also, galectins were differentially expressed in peripheral blood dendritic cell subsets; galectin-1 and galectin-9 were highly expressed in peripheral myeloid dendritic cells compared with plasmacytoid dendritic cells. We found that non-lesional as well as lesional skin samples from psoriasis patients had low levels of galectin-1 at the mRNA and protein levels, in parallel with low levels of IL-10 mRNA compared with skin from healthy patients. However, only lesional skin samples expressed high levels of Th1/Th17 cytokines. The analysis of galectin-1 expression showed that this protein was down-regulated in Langerhans cells and dermal dendritic cells as well as in peripheral blood CD11c(+) DCs from psoriasis patients. Expression of galectin-1 correlated with IL-17 and IL-10 expression and with the psoriasis area and index activity. Addition of galectin-1 to co-cultures of human monocyte-derived dendritic cells with autologous T lymphocytes from psoriasis patients attenuated the Th1 response. Conversely, blockade of galectin binding increased IFNγ production and inhibited IL-10 secretion in co-cultures of monocyte-derived dendritic cells with CD4(+) T cells. Our results suggest a model in which galectin-1 down-regulation contributes to the exacerbation of the Th1/Th17 effector response in psoriasis patients.

Eccrine squamous syringometaplasia secondary to cutaneous extravasation of docetaxel: report of three cases.

Eccrine squamous syringometaplasia is characterized by the metaplasia of cuboidal epithelial cells of the eccrine sweat ducts into squamous epithelial cells. It has been associated with several conditions including chemotherapy-related bilateral dermatitis, an entity that can take place in body areas rich in eccrine glands, as well as in acral erythema related to chemotherapy. Only a few cases because of cutaneous extravasation of chemotherapy have been previously reported. We report three cases of eccrine squamous syringometaplasia secondary to extravasation of docetaxel.

Sweet's syndrome with subcutaneous involvement associated with pegfilgrastim treatment: first reported case.

Neutrophilic panniculitis is an infrequent entity, considered by most authors as part of the 'neutrophilic dermatosis' spectrum. Few cases have been reported to be related with granulocyte colony-stimulating factor (G-CSF); we report a case of neutrophilic panniculitis and Sweet's syndrome lesions related with pegfilgrastim, a long-acting G-CSF. A 77-year-old woman with M2 acute myeloid leukemia was treated with chemotherapy as well as broad-spectrum antibiotics and antifungal drugs because of febrile neutropenia. Ten days after a single dose of pegfilgrastim, she developed a limited number of purple plaques on the neck, left leg, both arms and several indurated and slightly mobile nodules on her forearms. Skin biopsy of a plaque showed a diffused dermal neutrophilic infiltrate with dermal edema. Biopsy of a nodule showed a lobular neutrophilic panniculitis without vasculitis. No foreign material was found in those biopsies. No organisms were detected in blood, urine or tissue cultures. She was started with prednisolone 40 mg once a day, with dramatic improvement within the next 2 days. This case is noteworthy for the simultaneous appearance of Sweet's syndrome and neutrophilic panniculitis and it is the first case of neutrophilic panniculitis associated with this drug, pegfilgrastim.

Phototolerance induced by narrow-band UVB phototherapy in severe erythropoietic protoporphyria.

Erythropoietic protoporphyria arises from an inherited disorder of porphyrin metabolism which leads to an accumulation of protoporphyrin IX in the erythropoietic system and other tissues. It is characterized by cutaneous photosensitivity, usually difficult to keep under control. Among the scant therapeutic options proposed to reduce photosensitivity in erythropoietic protoporphyria, narrow-band UVB phototherapy has occasionally been used to induce sunlight tolerance. We report an adult case of erythropoietic protoporphyria with a severe photosensitivity treated with narrow-band UVB that developed an appropriate sunlight phototolerance, without adverse events during phototherapy.

Solar urticaria unresponsive to intravenous immunoglobulins.

The treatment of solar urticaria (SU) can be difficult. Only a few cases of SU have been treated with intravenous immunoglobulins (IVIg) (as monotherapy or combined with phototherapy), with reported fast and durable increase of solar exposure tolerance. A 61-year-old female with severe UVB- and UVA-induced SU and a 62-year-old female with severe UVA and visible light-induced SU were both treated with a single course of IVIg (total dose of 2 g/kg), infused over 3 days. Phototest, performed 3 months after the treatment, showed only a slight minimal urticating dose improvement, and both patients reported just a moderate and 'transient' subjective improvement. Our patient's poorer response, compared with previous reports, may be due to differences in IVIg's treatment schedules, which are reviewed.

Empyema necessitatis revisited.

Empyema necessitatis (EN) is a rare disease, with unknown incidence, which has received little attention from a dermatological point of view but it is essential to recognize it because of the possibility of causing mortality if not treated properly and in time. We report a 32-year-old woman, diagnosed with nervous anorexia, with an enlarging mass on the anterior right thoracic wall. Cultures showed Actinomyces gerencseriae as the main etiological agent of her empyema "necessitatis". She was successfully treated with amoxicillin with clavulanic acid. We found that 1) M. tuberculosis (35%) is still the most frequent agent, but Actinomyces (25%) and MRSA (10%) are becoming more relevant; 2) the most frequent dermatological finding is a subacute erythematous mass on costal wall; 3) new treatments have lowered mortality. Any enlarging and painful subacute thoracic mass with fluctuation should be considered as an EN suspicious lesion and the diagnostic approach must include a chest X-ray to rule out lung infection. Dermatologists should know about this infrequent entity in order to properly identify the potentially life-threatening process under these cutaneous lesions, achieving an early diagnosis and proper treatment.

Therapeutic drug monitoring of mycophenolic acid in patients with psoriasis.

Mycophenolate mofetil (MMF) has been shown to be effective in the treatment of psoriasis. MMF is the morpholinoethyl ester of mycophenolic acid (MPA), the active compound. Our objective was to characterize the pharmacokinetic profile of MPA in patients with psoriasis treated with MMF and to examine its correlation with effectiveness and toxicity. Eleven patients with moderate-to-severe chronic plaque psoriasis were treated with oral MMF 30 mg kg-1 daily over a period of 16 weeks. Patients were reviewed at 3, 8 and 16 weeks, checking the Psoriasis Area and Severity Index (PASI) and possible adverse events, and performing MPA C0 (trough) and C1 (1-hour post-dose) plasma levels. The reduction in PASI was statistically significant in all our patients. The drug was well tolerated. There was no significant correlation between C0 and C1 MPA levels and the reduction of PASI, improvement rates of PASI from baseline, weight of the patients and total dosage of MMF. Nevertheless, the highest detected mean levels of MPA C1 were observed in two of the patients with the highest improvement rate of PASI at the end of the study. Although C1 levels do not seem to strongly correlate with the effectiveness of the drug, the finding that the highest detected mean levels of MPA C1 were observed in two of the patients with the highest improvement rate of PASI suggests that the monitoring of C1 could be useful in some individual cases.

What characterizes the severity of psoriasis? Results from an epidemiological study of over 3,300 patients in the Iberian region.

BACKGROUND: Understanding the epidemiology of moderate-to-severe psoriasis is essential for its management. OBJECTIVE: To assess the epidemiological characteristics of patients with moderate-to-severe psoriasis. METHODS: Cross-sectional, observational epidemiological study conducted in Spain and Portugal. Data were collected by 332 dermatologists for >or=10 consecutive presenting patients. RESULTS: Based on body surface area (BSA) and Psoriasis Area and Severity Index (PASI) criteria, moderate-to-severe psoriasis was confirmed in >or=79.3% of patients (n = 3,320). Preexisting comorbid conditions included psoriatic arthropathy (13%), dyslipidemia (14.1%) and hypertension (20.2%). The mean BSA involvement was 23% (95% confidence interval, CI: 22.2-23.3%), and the mean PASI score was 14.3 (95% CI: 13.9-14.6%). During the 2 years prior to assessment, 97.0% of patients had received topical treatments, whereas 31.3% had not received systemic treatment or phototherapy. The median annual cost of treatment was 825 EUR. CONCLUSION: Moderate-to-severe psoriasis is accurately diagnosed, but inadequately treated in many patients in Spain and Portugal.

Lupus erythematosus panniculitis.

Lupus erythematosus panniculitis is an uncommon variant of lupus erythematosus characterized by a specific involvement of the subcutaneous fat. It is a panniculitis with peculiar clinical features and histopathologically characterized by a mostly lobular panniculitis. It may appear in patients with discoid lupus erythematosus and systemic lupus erythematosus, but also as the unique manifestation of lupus erythematosus, and in the latter cases the diagnosis may be problematic. Histopathologic differential diagnosis with subcutaneous panniculitis-like T-cell lymphoma may also be extremely difficult. This article reviews the salient clinicopathologic features and treatment of lupus erythematosus panniculitis, with special emphasis on the histopathologic features.

Subcutaneous sweet syndrome.

Neutrophilic panniculitis encompasses a heterogeneous group of diseases histopathologically characterized by an inflammatory infiltrate in the subcutaneous fat mainly composed of mature neutrophils. This group of panniculitides includes alpha(1)-antitrypsin deficiency, infectious panniculitis, factitious panniculitis, subcutaneous Sweet syndrome, neutrophilic/pustular panniculitis associated with rheumatoid arthritis, erythema nodosum-like lesions of Behçet disease, bowel bypass panniculitis, and iatrogenic panniculitis. This article reviews subcutaneous Sweet syndrome, which is a rare idiopathic panniculitis characterized by a dense neutrophilic infiltrate in the subcutis and is often related to hematologic malignancies. The relationship of subcutaneous Sweet syndrome and erythema nodosum is discussed as well as the differential diagnosis with other neutrophilic panniculitis.

Infective panniculitis.

Infective panniculitides are infections of the subcutaneous fat induced by any kind of micro-organism. They have rarely been considered as an entity within the spectrum of the panniculitis. Because of the increase in the immunosuppressive population, cutaneous infections' incidence is growing and atypical clinical presentations can be found. In this article, we analyze the etiology, clinical picture, histopathologic findings, diagnostics tools, and treatment of the more relevant infective panniculitis. We divide them according to the causative micro-organisms in bacterial, mycobacterial, fungal, and viral panniculitis.

[Schönlein-Henoch purpura with intestinal involvement: a clinic exposure]. / Púrpura de Schönlein-Henoch con afectación intestinal: exposición clínica.

Vasculitides are a group of diseases characterized by inflammation of the blood vessels and can affect any type of blood vessel in the body. Schönlein-Henoch purpura is a type of vasculitis secondary to hypersensitivity that affects the small blood vessels. Due to the rarity of this association, we present the case of a male patient with cutaneous purpura and intestinal involvement.

Eosinophilic folliculitis following allogeneic peripheral blood stem cell transplantation: case report and review.

Eosinophilic folliculitis is considered a heterogeneous group of disorders, with several clinical subsets, sharing a common histopathological appearance. Increasing numbers of cases, following bone marrow transplantation (BMT), have been reported in recent years. We herein present a case of eosinophilic folliculitis that appeared in a 26-year-old woman 5 months after allogeneic peripheral blood stem cell transplantation as treatment for eosinophilic acute leukemia. Our review of the published cases has shown that eosinophilic folliculitis in patients after BMT could be considered as a pattern of reaction related to immune dysregulation.