The tip of the iceberg of colorectal perforation from enema: a systematic review and meta-analysis.

BACKGROUND: Although rare, perforation following an enema used to treat constipation is a dangerous complication. However, no recommendations or guidelines for enema use are available. So, in common clinical practice, the diagnostic approach and the treatment are not standardized. In an attempt to resolve this clinical dilemma associated with high mortality and potential medicolegal claims for malpractice, we have performed a systematic review and meta-analysis of studies reporting on colorectal perforation secondary to enema use for adult patients with constipation. METHODS: A systematic search of PubMed, Web of Science and Scopus was performed according to the PRISMA statement up until February 2020. Studies that reported on colorectal perforation from enema use in adult patients with constipation were included. The primary outcomes were the rate of hospital mortality and pooled prevalence estimates of mortality from perforation secondary to enema use. The secondary outcomes were the administration of rectal enemas, site of visceral perforation, signs, symptoms, radiological evaluation, and type of treatment RESULTS: A total of 15 studies were included in the final analysis (49 patients). Across all studies, the pooled prevalence estimate of mortality for patients with perforation secondary to enema use was 38.5%, (95% CI [22.7%, 55.5%]). This rate was lower in patients who had surgery (35%) than in patients treated conservatively (57.1%). The sites of perforation were intraoperatively reported in 84% of cases, but in 16% of patients the rectal perforation was undiagnosed, and surgical decision making was problematic. The primary location of the perforation was the rectum in 80.9% of the patients. The enema was administered by a nurse in 90% of the cases, self-administered in 7.5% and a family doctor in 2.5%. The main objective of emergency surgery in this setting is resection of the perforation caused by the enema; when it is not possible to resect the perforated rectum, faecal diversion is needed. Hartmann's procedure was most commonly performed by the surgeons in this review (60.7%), with other reported treatments included a diverting proximal loop colostomy and sigmoid segment exteriorization CONCLUSIONS: Considering the studies available, it is not possible to undertake a thorough evaluation of enema use, including the associated complications and their management. Further data are required to allow the development of guidelines to advice on safe enema use and management of complications.

Autoantibody profile and clinical patterns in 619 Italian patients with cutaneous lupus erythematosus.

BACKGROUND: Anti-nuclear antibodies (ANA), anti-extractable nuclear antigens (ENA) and anti-dsDNA antibodies are often associated with cutaneous lupus erythematosus (CLE), with variable frequency depending on skin subtype. However, specific data based on large case-series on the pathogenetic, diagnostic and prognostic meaning of such autoantibodies are still lacking. OBJECTIVE: To characterize the correlations between CLE subtypes as well as LE-non-specific skin lesions and their autoantibody pattern. METHODS: Epidemiological, clinical and immunopathological data of 619 Italian patients with CLE and LE-non-specific skin lesions were analysed. Differences in age, sex, clinical features and autoantibody profile were evaluated in each LE subgroup. RESULTS: Anti-nuclear antibodies (P < 0.0001), anti-dsDNA (P < 0.0001), ENA (P = 0.001), anti-Sm (P = 0.001), anti-RNP (P = 0.004) and anti-histone (P = 0.005) antibodies were associated with SLE. A strong association between ANA (P < 0.0001) and anti-dsDNA (P < 0.0001) and female gender was also found: positive ANA and positive anti-dsDNA had a higher prevalence among females. Chronic CLE resulted to be negatively associated with ENA (OR = 0.51, P < 0.0001), anti-Ro/SSA (OR = 0.49, P < 0.0001) and anti-dsDNA (OR = 0.37, P < 0.0001). Intermittent CLE resulted to be negatively associated with ENA (OR = 0.50, P = 0.007) and ANA (OR = 0.61, P = 0.025). Subacute CLE resulted to be associated with ENA (OR = 5.19, P < 0.0001), anti-Ro/SSA (OR = 3.83, P < 0.0001), anti-Smith (OR = 2.95, P = 0.004) and anti-RNP (OR = 3.18, P = 0.007). Acute CLE resulted to be strongly associated with anti-dsDNA (OR = 6.0, P < 0.0001) and ANA (OR = 18.1, P < 0.0001). LE-non-specific skin lesions resulted to be significantly associated with systemic involvement. Livedo reticularis was significantly associated with ENA (P = 0.007) and anti-Ro/SSA (P = 0.036). Palpable purpura and periungual telangiectasia were significantly associated with ANA. CONCLUSION: According to our findings, some well-known associations between CLE subtypes and autoantibody profile were confirmed; moreover, specific association between autoantibodies and LE-non-specific skin lesions was highlighted. A strict association between anti-ENA and anti-Ro/SSA antibodies and livedo reticularis, ANA and palpable purpura, and ANA and periungual telangiectasia was evidenced.

Acne: a new model of immune-mediated chronic inflammatory skin disease.

Acne is a chronic inflammatory disease of the sebaceous-pilosebaceous unit. Interestingly, inflammation can be detected by histopathological examination and immuohistochemical analysis even in the apparently non-inflammatory acneic lesions, such as comedones. In the last years, it has been clearly demonstrated that acne development is linked to the combination of predisposing genetic factors and environmental triggers, among which a prominent role is played by the follicular colonization by Propionibacterium acnes (P. acnes). P. acnes displays several activities able to promote the development of acne skin lesions, including the promotion of follicular hyperkeratinisation, the induction of sebogenesis, and the stimulation of an inflammatory response by the secretion of proinflammatory molecules and by the activation of innate immunity, that is followed by a P. acnes-specific adaptive immune response. In addition, P. acnes-independent inflammation mediated by androgens or by a neurogenic activation, followed by the secretion in the skin of pro-inflammatory neuropeptides, can occur in acne lesions. In conclusion, acne can be considered as a model of immune-mediated chronic inflammatory skin disease, characterized by an innate immune response that is not able to control P. acnes followed by a Th1-mediated adaptive immune response, that becomes self-maintaining independently from P. acnes itself.

Cutaneous vasculitidis: histology and immunofluorescence.

Cutaneous vasculitis comprises a wide spectrum of diseases that involve predominantly the blood vessels and surrounding tissues of the skin. Few vasculitic syndromes have pathognomonic clinical, radiographic and/or laboratory findings; thus, confident and accurate diagnosis of vasculitis requires histological confirmation. Skin biopsy should be done, optimally within 24 to 48 hours after vasculitic lesions appear. Deep excision biopsy must be preferred. Direct immunofluorescence of lesional skin is helpful in the diagnosis of vasculitides in the light of a proper clinico-pathological setting and diagnostic in some peculiarly forms. Cutaneous histological patterns can be used to generate relevant clinical differential diagnoses, and, when coupled with patient's history, clinical and laboratory data, allow more precise and accurate diagnosis of vasculitic syndromes. This review will focus on histopathological and immunologic pattern of the more common cutaneous vasculitis syndromes, based on the 2012 Revised International CHCC.

Drug-induced cutaneous vasculitides.

Cutaneous vasculitides (CV) can be idiopathic or secondary to several triggers, including drugs, which account for up to 30% of all the cases of CV. Several drugs can induce CV, including some medications commonly used in dermatology, including minocycline, and several new drugs, such as anti-TNF agents. Different pathomecanisms are involved in the development of drug-induced CV, including the formation and deposition of immune complexes, the induction of neutrophil apoptosis, the formation of neoantigens between the drugs and proteins from the host, the shift of the immune response, and others. Although the diagnosis is difficult, because the clinical picture of drug-induced CV is in general indistinguishable from that of other forms of CV, it is important to recognize such entities in order to correctly manage the patient. Anamnesis, diagnostic algorithms to assess the likelihood of the association between a drug and a cutaneous reaction, skin biopsy and laboratory testing (including the search for antineutrophil cytoplasmic antibodies) are useful tools to make a diagnosis of drug-induced CV. About the therapy, while in idiopathic vasculitides the treatment is usually more aggressive and long-lasting, very often requiring a maintenance therapy with immunosuppressive drugs, in drug-induced CV the discontinuation of the suspected drug alone is usually enough to achieve complete remission, making the prognosis usually very good.

Drug induction in connective tissue diseases.

Connective tissue diseases (CTDs) are defined as a group of acquired disorders resulting from persistent immuno-mediated inflammation. Several classes of drugs seem to be capable of inducing or exacerbating CTDs. A drug-induced (DI) syndrome is defined as a condition temporally related to continuous drug exposure, which resolves upon drug discontinuation. Among CTDs, lupus erythematosus is the most widely known and investigated DI syndrome. However, in recent years, the association between the onset of other CTDs, such as dermatomyositis (DM) and morphea/systemic sclerosis (SSc) has increased in patients with preceding exposure to particular substances. Herein, we conducted a review of published case reports including DM and morphea/SSc, evaluating the real causality among drugs and these syndromes.

Clinical and immunopathological features of 159 patients with dermatitis herpetiformis: an Italian experience.

AIM: The aim of this paper to report the main clinical and immunopathological findings of our case series of 159 patients with dermatitis herpetiformis (DH). METHODS: All DH patients that were diagnosed from 1995 to 2012 at the Section of Dermatology of the University of Florence were included in the study. Clinical data were collected for each patient. Moreover, histopathological examination on both the skin and the small bowel, direct immunofluorescence on perilesional skin as well as the search for anti-endomysium and anti-tissue transglutaminsase antibodies (tTG) were performed. RESULTS: A total of 159 patients with a male predominance were enrolled. About 36% of the patients were below the age of 20. The most frequent clinical features seen in our DH patients were represented by figurate erythema, wheals, papules and scratching lesions, while the knees, elbows and buttocks were the most commonly involved sites. All the 22 patients that underwent a bowel biopsy showed the typical alterations found in celiac disease. Moreover, 100% of the patients showed granular IgA deposits at the papillary tips. Finally, anti-endomysium and anti-tTG antibodies were present in 90% and 96% of the patients, respectively. CONCLUSION: We reported one of the largest case series of patients with DH from a single center. Our study confirmed most of the data from the Literature, and in particular the association of DH to histologically proven CD in all the biopsied cases. Another interesting finding of our study is the high prevalence of DH within pediatric patients, that is usually underreported.

Multiple primary melanoma: the impact of atypical naevi and follow up.

BACKGROUND: Patients with melanoma are especially encouraged to have regular follow- up visits with their dermatologist and to perform total-body skin examination on a routine basis to identify new pigmented lesions or detect significant changes in existing naevi. OBJECTIVES: To identify main risk factors (sex, age, number of common and atypical naevi, family history, phototype) associated with multiple primary melanomas (MPM) and to investigate the association between regular follow up and tumour thickness of a second primary melanoma. METHODS: We performed a retrospective analysis of patients with MPM in order to evaluate risk factors for developing a second primary melanoma. Medical records of patients with melanoma who developed a second primary melanoma were selected from a database of all patients with histopathologically confirmed melanoma treated at the dermatology clinic of the University of Florence, Italy, from 2000 to 2004. Medical data culled from the patient records were as follows: medical history, number of typical naevi, presence of atypical naevi, Breslow thickness, Clark level and histotype of the melanomas, site of the melanomas and patient adherence to 6-month follow-up examinations. RESULTS: The presence of atypical naevi was associated with a higher risk of developing MPM (adjusted odds ratio 3·28, 95% confidence interval 1·35­7·44). Moreover, in the subjects who did not attend follow up, we noted that the thickness of the second melanoma was significantly higher, with a mean thickness of 1·22 mm, in comparison with patients with a careful adherence to follow up in whom the mean thickness was 0·36 mm (P = 0·0189). CONCLUSIONS: For the first time, the validity of this clinical approach has been supported by real comparison of thickness levels of second melanoma in patients with or without periodical follow up. Results obtained from this analysis show that follow up is an effective method for early detection of melanoma.