Intralesional Bleomycin Injections for Vascular Malformations: A Systematic Review and Meta-Analysis.

BACKGROUND: Vascular malformations are congenital anomalies of the vascular system. Intralesional bleomycin injections are commonly used to treat vascular malformations. However, pulmonary fibrosis could potentially be a severe complication, known from systemic bleomycin therapy for malignancies. In this study, the authors investigate the effectiveness and safety of bleomycin (A2, B2, and A5) injections for vascular malformations, when possible relative to other sclerosants. METHODS: The authors performed a PubMed, Embase, Cochrane Central Register of Controlled Trials, and gray literature search for studies (1995 to the present) reporting outcome of intralesional bleomycin injections in patients with vascular malformations (n ≥ 10). Predefined outcome measures of interest were size reduction, symptom relief, quality of life, adverse events (including pulmonary fibrosis), and patient satisfaction. RESULTS: Twenty-seven studies enrolling 1325 patients were included. Quality of evidence was generally low. Good to excellent size reduction was reported in 84 percent of lymphatic and 87 percent of venous malformations. Pulmonary fibrosis was never encountered. Meta-analysis of four studies on venous malformations treated with bleomycin versus other sclerosants showed similar size reduction (OR, 0.67; 95 percent CI, 0.24 to 1.88) but a significantly lower adverse event rate (OR, 0.1; 95 percent CI, 0.03 to 0.39) and fewer severe complications after bleomycin. Symptom relief, quality of life, and patient satisfaction were reported inadequately. CONCLUSIONS: The authors' data suggest that bleomycin is effective in reducing the size of lymphatic and venous malformations, and leads to a lower adverse event rate and fewer severe complications than other sclerosants. The included literature does not provide evidence that pulmonary fibrosis is a complication of intralesional bleomycin injections. This study represents the "best available" evidence; however, only low- to moderate-quality studies were available. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Propranolol versus corticosteroids: what should be the treatment of choice in infantile hemangiomas?

BACKGROUND: Infantile hemangiomas (IHs) are common and benign vascular tumors and usually involute spontaneously. Nevertheless, in some cases, treatment with systemic corticosteroids or propranolol is required. No randomized controlled studies, in which both treatment options were compared, have been performed. METHODS: A systematic literature review and a retrospective cohort study in the Academic Medical Centre of 56 patients (mean age, 5.5 months; range, 0-40 months; SD, 7.6) with IHs were carried out. These patients were treated with either systemic corticosteroids or propranolol. The outcomes of both treatment options were evaluated and compared. RESULTS: The literature review showed that propranolol resulted in an involution in 100% of the patients, whereas corticosteroids only reached involution in 89%. The mean first response of the IH to propranolol was 3.2 days and of corticosteroids was 8.5 days. In our study sample, the patients treated with propranolol showed a faster and better response than the patients treated with corticosteroids. This is in line with literature findings. CONCLUSIONS: Systemic propranolol treatment is more effective for IHs than systemic corticosteroid treatment. Secondly, propranolol elicits a faster response than corticosteroids.

Atopic eczema or atopiform dermatitis.

Age period prevalence of atopic eczema (AE), a very common skin disease, has increased during the past decennia. This expansion seems to be ending in wealthy countries, while an increase is observed in developing nations, for which there is no firm explanation. Recent steps in understanding AE are the detection of skin barrier related filaggrin null mutations in approximately 25% of patients and the recognition of IL-31 as a molecule possibly involved in the itch (pruritus). Also interesting are the recognition of thymus and activation-regulated chemokine (TARC) and proliferating-inducing ligand (APRIL), as being associated with AE severity and activity. Immunocentric and corneocentric views on pathogenesis (the inside-outside paradigm) and the diagnostic entity atopiform dermatitis (AFD) are discussed here. We emphasize that diagnosing AE is not simple but challenging. We accentuate that a diagnosis of AE is only possible when there is allergen-specific IgE. Advice as to the need for elimination of allergens and adjustment of lifestyle are only proficient in patients having atopy and true AE, not in those having AFD.

Clinical differences between atopic and atopiform dermatitis.

BACKGROUND: Atopic dermatitis (AD) has been divided into the "extrinsic" and "intrinsic" type, in which "intrinsic AD" is characterized by the absence of allergen-specific IgE. Still, there is no consensus whether this "intrinsic type" of AD, which we denominate as atopiform dermatitis (AFD), is a distinct entity. OBJECTIVE: A case-control study was performed to compare the clinical and diagnostic features of AD and AFD. METHODS: Patients with a clinical diagnosis of AD were selected. Cases did not have demonstrable allergen-specific IgE. Matched control subjects were tested positive for allergen-specific IgE. Patients were evaluated for medical history, quality of life, disease severity, and Hanifin and Rajka, U.K. and Millennium diagnostic criteria. RESULTS: Eight percent (n = 34) of the selected patients had, in fact, AFD. Female predominance, absence of atopic diseases, later onset of disease, and milder disease severity were observed in AFD. A history of atopy, recurrent conjunctivitis, palmar hyperlinearity, keratosis pilaris, pityriasis alba, and hand and/or food eczema were significantly less present in AFD. Dennie-Morgan fold was positively associated with AFD. LIMITATIONS: Not all patients with negative allergen-specific IgE participated and a relatively small number of AFD patients were studied. CONCLUSIONS: In addition to the absence of allergen-specific IgE, our findings support that AFD is an entity distinct from AD. With a distinction shown between AFD and AD, patient groups will be better defined and more homogeneous. Implications of this distinction will be of importance for preventive and therapeutic advice; diagnostic processes; and for future research.

Homozygous and compound heterozygous mutations in ZMPSTE24 cause the laminopathy restrictive dermopathy.

Restrictive dermopathy (RD) is a lethal human genetic disorder characterized by very tight, thin, easily eroded skin, rocker bottom feet, and joint contractures. This disease was recently reported to be associated with a single heterozygous mutation in ZMPSTE24 and hypothesized to be a digenic disorder (Navarro et al, Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet 13:2493-2503, 2004). ZMPSTE24 encodes an enzyme necessary for the correct processing and maturation of lamin A, an intermediate filament component of the nuclear envelope. Here we present four unrelated patients with homozygous mutations in ZMPSTE24 and a fifth patient with compound heterozygous mutations in ZMPSTE24. Two of the three different mutations we found are novel, and all are single base insertions that result in messenger RNA frameshifts. As a consequence of the presumed lack of ZMPSTE24 activity, prelamin A, the unprocessed toxic form of lamin A, was detected in the nuclei of both cultured cells and tissue from RD patients, but not in control nuclei. Abnormally aggregated lamin A/C was also observed. These results indicate that RD is an autosomal recessive laminopathy caused by inactivating ZMPSTE24 mutations that result in defective processing and nuclear accumulation of prelamin A.

Quality of life in patients with vascular malformations of the lower extremity.

With the exception of capillary malformations (port-wine stains), the adverse psychosocial effects of vascular malformations have not received much attention in the medical literature. We, therefore, studied health related quality of life of patients with vascular malformations located primarily on the lower extremity, who presented to us over a 10-year period. Patient's self-assessment of quality of life was measured by the Multiple Outcomes Study (MOS) Short Form Health Survey Questionnaire (SF-36). Several possible predictors were also examined. Eighty-one patients (33 male, 48 female), aged 14-61 years, completed the SF-36. Seventy-one patients (88%) had a low flow lesion. Twenty-three patients (28%) had hypertrophy of the lower extremity, while 11 patients (14%) had hypotrophy. Sixty-nine patients (85%) had the vascular malformation located only on the lower extremity. Six (7%) also had their upper extremity (hand) involved, and 20 patients (24.7%) had >10% TBSA affected. Eight patients (10%) needed special shoes. Fifty-one patients (63%) had a previously performed MRI, of which 62.7% (32/51) had muscle involvement. Fifty-one patients (63%) had been operated on. Of the 34 patients wearing elastic compression stockings, 25 patients (74%) indicated that they were satisfied with the stockings. Compared to the general population sample, the SF-36 questionnaire indicated that our vascular malformation patients reported impaired vitality and higher levels of pain, while no differences were seen regarding the other dimensions of quality of life. Demographic, clinical and therapy characteristics could explain quality of life only to a limited extent. Explained variability of the SF-36 dimensions ranged from 0% for mental health to 34.5% for role functioning physical. To our surprise, this study suggests that patients with vascular malformations located primarily on the lower extremity do not have a greatly decreased quality of life when compared to the general Dutch population.

A novel connexin 26 mutation in a patient diagnosed with keratitis-ichthyosis-deafness syndrome.

Keratitis-ichthyosis-deafness syndrome is a rare disorder characterized by erythrokeratoderma, deafness, and keratitis. Scarring alopecia and squamous cell carcinoma can also occur. Most cases described so far were sporadic. Here we present evidence that keratitis-ichthyosis-deafness syndrome is caused by a mutation in the connexin 26 gene. This finding expands the spectrum of disorders caused by defects in connexin 26 and implies the gene in normal corneal function, hair growth, and carcinogenesis.