Use of imatinib in a patient with cutaneous vasculopathy in the context of von Recklinghausen disease/neurofibromatosis.

von Recklinghausen disease/neurofibromatosis (NF) is caused by an autosomal dominant mutation in NF1, resulting in a deficiency of neurofibromin 1, a protein with a tumour suppressor function in the Ras-extracellular regulated kinase pathway. The disease comprises a variety of clinical manifestations, including vascular abnormalities. Large vessel abnormalities are well known, while small vessels of the skin are very rarely involved. The latter can cause livedo, necrosis and painful ulcers. For such ulcers, all invasive therapies (e.g. surgery and radiotherapy) are harmful and should be avoided. Herein, we describe a patient with NF and cutaneous vasculopathy treated with imatinib, a tyrosine kinase inhibitor.

Effect of TEX-OE(®) treatment on the development of heat shock proteins in commercial broiler chicks and the impact on performance indicators in the grow-out period.

Heat shock proteins (HSPs) are highly conserved proteins, shown to protect organisms against physical and physiological stress. TEX-OE(®) is a patented total extract of the fruit of Opuntia ficus indica, which has been demonstrated to accelerate the development of HSPs in several animal species. One-day-old commercial broiler chicks were treated with TEX-OE(®); HSP was measured by enzyme-linked immunosorbent assay (ELISA), and a large commercial field trial investigated key performance indicators (KPIs) in treated versus untreated controls chicks. TEX-OE(®) significantly increased HSP concentrations in treated chicks versus controls. Final cumulative mortality, liveweight and percentage factory-rejects were better than in controls. The accelerated HSP response may enable chicks to cope with early stressors, which is reflected in improved KPIs.

[Cutaneous B-cell lymphoma]. / Lymphomes B cutanés: diagnostic et prise en charge.

Primary cutaneous B-cell lymphomas (PCBCL) present as skin lesions without evidence of extracutaneous involvement at diagnosis. This article summarizes clinical and histopathological features of the three main types of PCBCL: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type. It will discuss initial staging procedures, necessary to differentiate PCBCL from systemic lymphoma with secondary skin involvement. Finally, we will review the main treatments, local therapy (radiotherapy, surgical excision) for indolent PCBCL and multiagent chemotherapy for primary cutaneous diffuse large B-cell lymphoma, leg type.

[Case report: unusual clinical presentation of a follicular lymphoma]. / Présentation atypique d'un lymphome B centrofolliculaire.

Follicular lymphoma is an indolent B-cell lymphoma. Fluctuant asymptomatic lymphadenopathies are their usual clinical manifestation. B-cell neoplasms can sometimes involve the skin. In this case, it is important to distinguish a systemic B-cell lymphoma with secondary skin involvement from primary cutaneous lymphoma. Immunohistochemical stainings and staging usually allow to make the difference. Here we report the first case of a systemic follicular lymphoma with secondary cutaneous involvement presented with papular lesions on the face mimicking a rosacea.

Subcutaneous fasciotomy and eradication of superficial venous reflux for chronic and recurrent venous ulcers: mid-term results.

OBJECTIVE: Increased intramuscular and subcutaneous tissue pressures are often found in patients with severe chronic venous insufficiency venous ulcer disease. Additional subcutaneous para-tibial fasciotomy promotes early ulcer healing. This study evaluates the mid-term effect of eradication of superficial reflux with additional fasciotomy in patients with increased tissue pressures. METHOD: Between January 2006 and June 2009, 58 patients underwent fasciotomy. Tissue pressures (intramuscular and subcutaneous) were measured. Sixty-nine limbs with 91 venous ulcers were treated. Mean duration of the venous ulcer was 3.4 years. Underlying disease was post-thrombotic syndrome (PT) in 19 patients (33%, 24 limbs, 27 ulcers) and non-post-thrombotic (non-PT) severe chronic venous insufficiency in 39 (67%, 45 limbs, 64 ulcers). All patients were C6 at the time of surgery. Preoperative tissue pressures were 23.5 ± 6.1 mmHg (intramuscularly) and 9.8 ± 3.2 mmHg (subcutaneously). RESULTS: Ninety ulcers (99%) healed postoperatively (42 with and 48 without skin grafting). Tissue pressures significantly decreased following surgery and remained low at three months postoperatively. Ten ulcers in six patients recurred six to 20 months postoperatively (11%), resulting in 86.4 actuarial freedom from venous ulcer recurrence at three years following surgery. Four patients (1 non-PT and 3 PT) had re-fasciotomy; all healed initially but two ulcers (2 patients, PT) recurred at 11 and 12 months. Those patients underwent re-fasciotomy, one healed and one recurred six months later. CONCLUSION: Eradication of superficial reflux with additional subcutaneous fasciotomy for chronic and recurrent venous ulcer improves ulcer healing or success of skin grafting. Mid-term results are excellent particularly in patients with non-PT disease. Recurrence is more frequently seen in patients with PT syndrome. In patients with ulcer recurrence and high tissue pressures, re-fasciotomy can be helpful to promote healing, particularly in patients with primary venous disease.

Tuberculous Cutaneous Ulcers Associated with Miliary Tuberculosis in an Elderly Woman.

Skin localizations in disseminated tuberculosis may present a clinical resistant evolution. An 81-year-old woman, treated by long-term steroids and methotrexate for rheumatoid polyarthritis, developed a disseminated tuberculosis in chest, bones and skin. While pulmonary symptoms quickly improved under conventional tuberculostatic drugs, skin ulcers showed positive cultures for 5 months and healed after 12 months of treatment.

Amicrobial pustulosis of the folds associated with auto-immune disorders. A case report with an analysis of cytokine expression profile in skin lesions of cutaneous neutrophilic lupus.

A new entity was described by Crickx et al. in 1991, associating amicrobial pustulosis of the folds with systemic lupus erythematosus in young females. It is proposed to regroup this entity under the name of 'neutrophilic cutaneous lupus'. We report a case of a 13-year-old girl with a pustular eruption of the cutaneous folds and scalp associated with undetermined connective tissue disease. We performed a screening for the expression of 174 cytokines in the pustules and compared it with other pustular diseases (acne flare, acute generalized exanthematous pustulosis, pustulosis of Sneddon and Wilkinson). Matrix metalloproteinase 9 and Siglec-5 (CD170) were highly expressed in all types of pustules and reflect high neutrophil density. Amicrobial pustulosis of the folds was characterized by a higher expression of interleukin (IL) 1alpha, IL-2 receptor alpha, macrophage colony-stimulating factor, insulin-like growth factor binding protein 1, brain-derived neurotrophic factor, tumour necrosis factor (TNF) alpha and a lower expression of CD14, IL-1beta, IL-12, soluble TNF receptors I and II, growth-regulated oncogene alpha, fibroblast growth factor 4 and vascular endothelial growth factor as compared to the controls.

Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients.

BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by the association of skin lesions, hearing loss and vascularizing keratitis. KID syndrome is caused by autosomal dominant mutations in the connexin 26 gene (GJB2). OBJECTIVES: To establish whether there is a correlation between genotype and phenotype in KID syndrome. METHODS: Clinical examination and molecular analysis of GJB2 were performed in a cohort of 14 patients with KID syndrome originating from 11 families. We also reviewed the 23 cases with molecular analysis previously reported in the literature. RESULTS: The patients displayed the classical signs of KID syndrome with the additional finding of inflammatory nodules in six patients (43%); this clinical finding has not been described previously in the literature. One patient presented at the age of 18 years with a fatal carcinoma of the tongue, an extremely rare reported complication. For seven of the 11 families (64%) the disease was sporadic, whereas it was familial in the remaining four families (36%). Twelve patients (86%) were heterozygous for the p.Asp50Asn mutation and two patients (14%) were heterozygous for the p.Ser17Phe mutation. Surprisingly, a family in which we personally examined the healthy parents had two affected children heterozygous for the p.Asp50Asn mutation, suggesting germinal mosaicism. Compared with patients with the p.Asp50Asn mutation, the two patients with the p.Ser17Phe mutation had more severe skin involvement. One of these two patients experienced a carcinoma of the tongue. CONCLUSIONS: Familial cases appear to be more frequent than reported in the literature. The possibility of germinal mosaicism must be taken into account for genetic counselling. This study also suggests that patients with the p.Ser17Phe mutation may have a more severe phenotype and could be at higher risk for tongue carcinoma.

Effect of tuberculin skin testing on a Mycobacterium tuberculosis-specific interferon-gamma assay.

Recently, interferon-gamma release assays (IGRA) for specific diagnosis of Mycobacterium tuberculosis infection have become available. In recent UK tuberculosis (TB) guidelines, it has been advised to screen for latent M. tuberculosis infection using the tuberculin skin test (TST), followed by IGRA if the TST is positive. Since TST can boost immune responses to tuberculin, the present authors evaluated whether TST administration affects the result of QuantiFERON-TB Gold in-tube (QFT-GIT), a whole blood-based IGRA. QFT-GIT was performed on the day of TST administration and the day of reading in 15 TST-negative subjects, 46 TST-positive subjects with recent or remote exposure to M. tuberculosis and five cured TB patients. No systematic boosting of QFT-GIT responses from negative to positive was observed. Only in a few TST-positive persons did TST enhance pre-existing QFT-GIT responses. Screening for latent Mycobacterium tuberculosis infection using tuberculin skin testing followed by interferon-gamma release assays on the day of reading is a reliable approach, as the specificity of QuantiFERON-TB Gold in-tube is not affected by prior tuberculin skin test administration.

Intralesional and intravenous treatment of cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: report and follow-up of eight cases.

BACKGROUND: Rituximab (MabThera); Roche, Basel, Switzerland; an anti-CD20 chimeric monoclonal antibody) has been shown to have significant activity in nodal B-cell lymphomas, with few associated adverse effects. Its efficacy and safety were first demonstrated in the treatment of systemic B-cell lymphomas. Intravenous and subsequently intralesional administration of rituximab have also been reported to be effective and well tolerated in cutaneous B-cell lymphoma (CBCL). The comparative efficacy of intravenous vs. intralesional rituximab in CBCL is not known. OBJECTIVES: To evaluate the objective response rate, relapse rate, time to progression, and tolerance in patients with CBCL treated with intravenous or intralesional rituximab. METHODS: Eight patients with multiple primary CBCL (four follicle centre lymphoma and four marginal zone lymphoma) were treated with intralesional rituximab (six patients; 10-30 mg per lesion, three times weekly for one or two cycles at a 4-week interval) or intravenous rituximab (two patients; 375 mg m(-2) once weekly for four consecutive weeks). RESULTS: Complete clinical remission was obtained in all cases. The two patients treated intravenously did not relapse during a follow-up period of 18-24 months. Four of six patients treated intralesionally presented a relapse of new lesions at another site within a mean of 6 months after treatment. The injected lesions did not, however, recur. New lesions also responded to another cycle of intralesional rituximab. Tolerance to treatment was very good in both treatment groups. CONCLUSIONS: Rituximab therapy of CBCL appears to have a potential advantage in cases where lesions are localized in sites that are difficult to treat with radiotherapy or surgery and in which secondary scarring or alopecia is likely. Intralesional injections of rituximab allow the use of considerably smaller doses compared with intravenous treatment, with similar response rates and tolerance. However, within a 12-month follow-up period, relapse of CBCL with new lesions at distinct sites was frequently observed after intralesional treatment.

Regression of extranodal natural killer/T-cell lymphoma, nasal type with denileukin diftitox (Ontak) and bexarotene (Targretin): report of a case.

Denileukin diftitox (Ontak) is a fusion protein comprising a diphtheria toxin and an interleukin (IL)-2 moiety that specifically targets CD25 (IL-2 receptor)-positive tumour cells. We report a patient with rapidly progressive Epstein-Barr virus-positive nasal type extranodal natural killer/T-cell lymphoma (extranodal NKTCL), treated with a combination of denileukin diftitox (Ontak) and oral bexarotene (Targretin). A significant regression of the cutaneous tumours was observed already after the first cycle of denileukin diftitox and was maintained for a period of 5 months with monthly cycles of denileukin diftitox. The treatment was well tolerated. Following this response the patient decided to stop the treatment. He was then followed by his oncologist and lost from dermatological follow-up. Shortly after treatment withdrawal the disease progressed and the patient received one cycle of doxorubicin (Caelyx). He died from septic shock syndrome 2 months later. To our knowledge this is the first case of extranodal NKTCL treated with denileukin diftitox and bexarotene. A striking, albeit transient, response occurred with this therapy. Combination treatment with denileukin diftitox and bexarotene should be further assessed in this aggressive type of cutaneous lymphoma.

[Cutaneous complications of anti-hypertensive drugs]. / Complications cutanées des traitements anti-hypertenseurs.

Anti-hypertensive drugs are prescribed frequently and can cause cutaneous adverse drug reactions. The extent of this side effect accounts for about 10-60% of the total adverse drug reactions due to antihypertensive drugs. This review analyses anti-hypertensive drugs by class and examines various cutaneous pathologies that could be related to these treatments. We also call attention to the serious and potentially lethal cutaneous complications linked to these drugs.

Dermoscopy for the in vivo detection of sarcoptes scabiei.

We report the case of an 80-year-old patient who had intense pruritus which did not respond to a 3-month treatment with topical corticosteroids. On dermoscopy examination of the excoriations, we found the typical dermoscopic aspect of the scabies mite at a distance. Dermoscopy allows identifying a triangular structure which corresponds to the anterior section of the mite including the mouth part and the 2 pairs of front legs. This aspect has been described as resembling a jetliner with its trail, a delta glider or a spermatozoid. Traditional diagnostic methods for scabies failed in this case because the mites were at a distance from the burrows. This was due to the fact that the reaction to the mite was less pronounced and the diagnosis is frequently missed. Dermoscopy is a useful tool for the diagnosis of scabies either as a diagnostic test or to guide the traditional diagnostic tests.

Fulminant herpetic sycosis: atypical presentation of primary herpetic infection.

Fulminant herpetic sycosis is a rare but well-known manifestation of herpes simplex virus (HSV) infection occurring in the context of viral recurrence in immunodepressed patients. We present here the case of a 32-year-old male patient, without notable medical history, who developed papulovesicular lesions of the beard accompanied by fever, painful cervical lymphadenopathy and odynophagia, with a clinical evolution that was initially unfavourable under antibiotic treatment. The diagnosis of herpetic sycosis was established by means of direct immunofluorescence and culture which confirmed positivity for HSV-1 and serologies compatible with a primary viral infection. No sign for a latent immune deficit was found at the time of investigations. The clinical evolution was rapidly favourable with administration of intravenous aciclovir for 1 week. To our knowledge, herpetic sycosis as a presentation of primary viral infection has not been reported previously. The possibility of a herpetic sycosis of the beard must be considered in the case of non-response to antibiotic or antifungal treatment.

Erosive pustular dermatosis of the leg: report of three cases.

Erosive pustular dermatosis of the leg is a distinct form of spongiform amicrobial pustulosis. The disorder typically affects the lower limbs of elderly patients presenting with chronic venous insufficiency and stasis dermatitis, and has a chronic course. Three elderly patients with chronic venous ulcers are described, who developed pustules and moist eroded lesions on the leg. The clinical and histological features were typical for erosive pustular dermatosis. The lesions rapidly responded to topical treatment with either tacrolimus or corticosteroids. Of note, this condition was associated with a diverticular disease in two patients, while in another patient an epidermoid carcinoma of the tongue was present. Erosive pustular dermatosis of the leg is an uncommon but distinct skin disorder typically associated with trophic changes of the lower limbs. Our observations raise the question of the relation of erosive pustular dermatosis of the leg with the group of neutrophilic dermatoses. Topical immunotherapy with tacrolimus may constitute a novel therapeutic option for this frequently recalcitrant condition.

Acute generalized exanthematous pustulosis associated with STI571 in a patient with chronic myeloid leukemia.

The tyrosine kinase inhibitor STI571 is a novel promising class of anticancer drugs. We report a case of cutaneous adverse reactions to STI571 in a young woman with blast crisis of chronic myeloid leukemia. She had first typical acute generalized exanthematous pustulosis mimicking mercury rash and then urticarial eruption. We suggest that cell pathways mediated by some tyrosine kinases might be involved in the pathogenesis of these skin eruptions.

JC virus T' proteins encoded by alternatively spliced early mRNAs enhance T antigen-mediated viral DNA replication in human cells.

Alternative splicing of the JC Virus (JCV) precursor early mRNA yields five transcripts that encode proteins that regulate the life cycle of this human polyomavirus. Large T protein (TAg) mediates viral DNA replication and oncogenic activities, and small t protein influences these functions under certain conditions. Recently, three new early proteins, T'(135), T'(136), and T'(165), were discovered that contain sequences overlapping amino-terminal TAg functional domains. Initial studies with the T' proteins suggested they contribute to viral DNA replication and transformation. Mutation of a donor splice site utilized by all three T' mRNAs creates a mutant that exhibits a 10-fold decrease in viral DNA replication compared to wild type JCV. To assess the influence that individual T' proteins have on the replication process, a set of T' acceptor site mutants was created in which the unique second acceptor splice site of each T' mRNA was altered to eliminate production of one, two or all three T' mRNAs. The patterns of early mRNA and protein expression in these seven mutants were examined, and it was found that mutation of the T'(135) acceptor site resulted in the utilization of cryptic splice sites and the generation of new T' species. Additional mutations were made to prevent these aberrant splicing reactions prior to measuring DNA replication potential of the mutants. DpnI assays revealed that each T' protein contributes to TAg-mediated DNA replication activity. The three single mutants that express two T' proteins and the double mutant that only produces T'(136), exhibited levels of replication equivalent to that of wild type virus, whereas the two double mutants that fail to express T'(136) replicated about twofold less efficiently than wild-type JCV. Replication activity of the triple acceptor site mutant, like that of the T' donor site mutant from an earlier study, was impaired significantly.

Chronic borreliosis presenting with morphea- and lichen sclerosus et atrophicus-like cutaneous lesions. a case report.

We report on a case of chronic cutaneous borreliosis with manifestations clinically compatible with morphea and lichen sclerosus et atrophicus. The histopathologic features of these lesions were those of acrodermatitis chronica atrophicans. Our case illustrates the concept that clinical aspects of morphea and lichen sclerosus et atrophicus pertain to the spectrum of cutaneous borreliosis.