Allergen-specific immunotherapy with apples: selected cultivars could be a promising tool for birch pollen allergy.

BACKGROUND: Most birch pollen-allergic patients develop allergic cross-reactions to the major allergen found in apples Mal d1, known as pollen-related food allergy (prFA). This is due to a strong clinically relevant homology between the major allergen in birch Bet v 1 and Mal d 1. Daily apple consumption induces oral tolerance in prFA, but its effect on the inhalational allergy has not been investigated. OBJECTIVES: As continuous apple consumption might also mitigate the inhalational allergy, this study aimed to uncover apple cultivars suitable for treatment of birch pollen rhinoconjunctivitis and apple allergy in a controlled and established dosage. METHODS: Patients (n = 52) with birch pollen allergy and prFA to apples were subjected to a prick-to-prick test (SPT) with 23 cultivars (red-fleshed, old traditional and new commercial). By SPT, the apple parts flesh, peel equatorial and peel apical near the stalk were compared for their reactivity. One apple cultivar of each allergenicity class (low, middle and high) was subsequently tested in an oral provocation test (OPT). RESULTS: According to the SPTs, we provide a ranking of all 23 cultivars. Red-fleshed apples displayed the lowest reactivity, followed by old and new cultivars. Four cultivars showed disagreement from their allergenicity class: Santana and Pink Lady®, new cultivars that provoked only low to moderate. In contrast, White Rosemary and Goldparmäne, two old cultivars, induced strong reactions. Skin reactivity increased from flesh to peel to stalk, and SPT results could predict the severity of prFA of each allergenicity class. CONCLUSIONS: Herein, we propose a treatment protocol for allergen immunotherapy to birch pollen and prFA with daily apple consumption. Red-fleshed, old and the new cultivars Santana and Pink Lady® provoke less allergic reactions and are suitable for initial induction. After a controlled and well-tolerated increase of intake, also moderate and finally high allergenic apple cultivars should be integrated into treatment of birch pollen allergenic patients.

Analysis of effectiveness and safety of a three-part triage system for the access to dermatology specialist health care.

BACKGROUND: Accessibility and waiting times pose a general problem in public financed health care systems. In Italy a three-part triage system (urgent, priority and deferrable with a corresponding maximum time target before treatment of 1, 8 and 60 days respectively) to gain faster treatment for urgent and emergent cases of dermatology outpatients has been introduced. METHODS: From February 2011 to August 2013, samples of 1526 outpatient electronic medical record cases were randomly retrieved. Diagnoses with their corresponding triage codes were recorded. Urgent visits were further analysed according to the referring physician. The appropriateness of the referral was based on the published state law diagnostic guidelines. Data were statistically analysed using the 2-tailed Pearson chi-squared test or the Fisher exact test. RESULTS: Overall, 56.5% retrieved cases were deferrable, 13.1% priority and 30.4% urgent. Frequency of diagnoses differed significantly between the three groups (P < 0.05). Appropriateness of the triage level was higher for priority than for urgent referrals (P < 0.05%). An overestimation of urgency levels was noted and urgent cases were not overseen. Triage levels were best assessed by general practitioners (75% correct allocations) followed by emergency physicians (59%) and other specialists (45%) (P < 0.01%). CONCLUSION: The triage system according to clinical need is safe. Correct allocation according to urgency occurs in <75% and leaves space for improvement. General Practitioners address patient's access significantly better than other physicians, therefore are best suited to function as gatekeepers to the access of specialist care in public funded health care systems.

Melanoma incidence and Breslow tumour thickness development in the central Alpine region of South Tyrol from 1998 to 2012: a population-based study.

BACKGROUND: Cutaneous melanoma incidence is increasing worldwide, especially for in situ and thin (<1 mm) lesions, while thick (≥1 mm) lesions have been generally stable in many studies; although epidemiological data on melanoma is readily available, population-based studies, especially on mountain regions, are rare. OBJECTIVE: The aim of this study was to analyse cutaneous melanoma incidence and Breslow tumour thickness in the central Alpine mountain region of South Tyrol, northern Italy. METHODS: All newly diagnosed cutaneous in situ and invasive melanomas in the resident population from 1998 to 2012 were taken from the Pathology Unit, Bolzano Hospital and South Tyrol Cancer Registry. Incidence and Breslow tumour thickness were analyzed. Statistical analyses included Mann-Whitney and Kruskal-Wallis tests. RESULTS: A total of 784 in situ melanomas and 1663 invasive melanomas were collected. In situ melanomas showed the highest increase: European age-standardized incidence rose from 2.44 per 100,000 inhabitants in 1998-2002 to 16.01 in 2008-2012. Invasive melanoma incidence increased from 12.69 in 1998-2002, to 22.88 in 2008-2012. The incidence rise was observed in thin melanomas (from 8.39 to 16.18) and in thick melanomas (from 4.30 to 6.70). Breslow distribution revealed a median value of 0.62 mm (mean 1.34; SD 2.24; range 0.09-30.0) and did not change significantly over time (P = 0.286). Higher Breslow values were observed at advanced age (P < 0.001), among males (P = 0.017), in nodular melanomas (P < 0.001) and at higher Clark levels (P < 0.001). Significant differences were also found in urban hospitals compared to rural hospitals during the whole period (P = 0.004), but not in the last 5 years (P = 0.053). CONCLUSION: Incidence of cutaneous melanoma is increasing in South Tyrol, especially for in situ and thin lesions, but also for thick lesions; no reduction in median tumour thickness is observed. Rural areas and elevated altitudes may contribute to this effect.

Premature newborns with fatal intrauterine herpes simplex virus-1 infection: first report of twins and review of the literature.

BACKGROUND: Neonates with blistering skin diseases are dermatologic emergencies. The pathologies involved can pose diagnostic difficulties and there exists a variety of potential life-threatening differential diagnoses. OBJECTIVE: description of the first case of intrauterine acquired herpes simplex virus (HSV) 1 infection in twins. METHODS: We present the case of two premature bicordial biamniotic twins (27th week of gestation) whose intrauterine growth retardation, fetal anaemia and cardiotocography abnormalities led to a caesarean emergency delivery. RESULTS: Accurate medical history revealed a maternal febrile gingivostomatitis at the 23rd week of gestation, which was neglected by the treating gynaecologist. Respiratory distress was present at delivery and intubation was necessary in both children. The whole skin showed extensive erosions and ulcerations and the mucosa of the eyes and genitals was also involved. Intrauterine Herpes simplex virus (HSV) 1 infection was confirmed by immunohistochemistry of skin Tzanck smear (HSV 1 positive, HSV 2 negative), real-time polymerase chain reaction of both serum and skin (HSV 1 positive; HSV 2 negative) and maternal serology positive for HSV 1 IgM and IgG. Siblings were immediately treated with high-dose endovenous acyclovir. Anaemia thrombocytopenia and hepatorenal values markedly deteriorated and both developed consequential hepatorenal failure. The third day live supportive measures were terminated after parental informed consent and both siblings deceased shortly after on their mother's breast. DISCUSSION: Intrauterine HSV infection is rare and accounts only for 5% of neonatal HSV infections. Literature reports only 64 cases and 90% of those are related to HSV-2. Transplacental viral transmission is highest during the first 20 weeks of gestation and has been observed in pregnant women with disseminated HSV infection. Mortality and morbidity of intrauterine herpetic infection are extremely high. CONCLUSION: Despite transplacental HSV transmission remains a rare event, the potential devastating outcome justifies immediate adequate antiviral treatment in a pregnant woman affected by primary HSV infection.

Congenital disseminated HSV-1 infection in preterm twins after primary gingivostomatitis of the mother: case report and review of the literature.

Transplacental transmission of HSV infection is rare, typically associated with Herpes Simplex Virus 2 (HSV-2) and often reported in term infants, whereas only a few cases of preterm infants with Herpes Simplex Virus 1 (HSV-1) infection are found in the literature. We report the case of a transplacental HSV-1 infection in preterm twins born at 27 weeks gestation. At 23 weeks gestation the mother had experienced primary gingivostomatitis and "flu-like" symptoms, which healed without specific treatment. At birth both infants presented disseminated ulcerated skin lesions at the head, trunk and extremities. Soon after birth, the infants required mechanical ventilation and showed multiple organ involvement. On the basis of the mother's positive HSV-1 serology, treatment was established before the Tzanck test, serological findings and polymerase chain reaction of the skin and blood had confirmed the neonatal infection. In spite of the early diagnosis within hours after birth and immediate treatment, the extensive skin involvement associated with rapidly progressing multiorgan failure resulted in death of both infants within 3 days. Although a primary HSV-1 infection during pregnancy is extremely rare, gingivostomatitis with general symptoms can lead to transplacental infection and should therefore be taken seriously. Prompt recognition and treatment in the mother are paramount and might be life-saving for the infants.

Comparative analysis of immunohistochemistry, polymerase chain reaction and focus-floating microscopy for the detection of Treponema pallidum in mucocutaneous lesions of primary, secondary and tertiary syphilis.

BACKGROUND: The incidence of syphilis is increasing in many parts of the world including a re-emergence in Western Europe and North America. Depending on the disease stage, direct detection of Treponema pallidum in mucocutaneous lesions of syphilis may be difficult and histopathological findings are not always straightforward. Thus, the correct histological diagnosis may be challenging. OBJECTIVES: Comparatively to evaluate the evidence for infection with T. pallidum by immunohistochemistry (IHC), polymerase chain reaction (PCR) and focus-floating microscopy (FFM). METHODS: A series of 86 paraffin-embedded skin biopsy samples from patients with primary, secondary or tertiary syphilis was assessed for detection of T. pallidum by IHC and FFM; 45 specimens were also investigated by a T. pallidum-specific PCR analysis. Histopathological reaction patterns and number and distribution of treponemes were studied, and all data were re-evaluated by clinicopathological correlation. RESULTS: Using a polyclonal antibody directed against T. pallidum, we detected the presence of T. pallidum by IHC in 42/86 (49%) samples [6/9 (67%) primary, 34/62 (55%) secondary and 2/15 (13%) tertiary syphilis]. T. pallidum-specific DNA was detected in 31/45 (69%) specimens [4/4 (100%) primary, 26/34 (76%) secondary and 1/7 (14%) tertiary syphilis]. In comparison, FFM analysis resulted in an overall detection rate of 82/86 (95%) [9/9 (100%) primary, 60/62 (97%) secondary and 13/15 (87%) tertiary syphilis]. Significant differences were observed concerning amount and distribution of organisms (epitheliotropic vs. endotheliotropic) in correlation to the three disease stages and to histopathological reaction patterns. CONCLUSIONS: FFM is a highly sensitive and specific method to detect T. pallidum in tissue from mucocutaneous syphilis lesions. Our results indicate that a combination of PCR and FFM, as the most sensitive approach, could provide an additional benefit for the histopathological diagnosis of (late) secondary and tertiary syphilis and may be helpful in cases where serological testing of T. pallidum antibodies has failed, but the clinical suspicion for syphilis remains.

[Erythema annulare centrifugum. A clinical reaction pattern]. / Erythema anulare centrifugum. Ein klinisches Reaktionsmuster.

Erythema annulare centrifugum (EAC) is a clinical reaction pattern and not a specific clinicohistologic entity. The clinical and histologic differential diagnosis of EAC should take at least three main disease groups into consideration, which are often classified under this disorder: (tumid) lupus erythematosus, spongiotic dermatitides, and pseudolymphomas.

New concepts on erythema annulare centrifugum: a clinical reaction pattern that does not represent a specific clinicopathological entity.

BACKGROUND: Erythema annulare centrifugum (EAC) is considered an inflammatory skin disease with unknown aetiology. In most textbooks it is assigned to the incoherent conglomeration of figurate or gyrate erythemas. OBJECTIVES: To re-evaluate a large cohort of patients with EAC and to assess the evidence for infection with Borrelia. METHODS: We retrospectively investigated 90 cases with the diagnosis of EAC. Haematoxylin and eosin sections were re-examined and diagnoses were specified; these were then confirmed by clinicopathological correlation. Infection with Borrelia was assessed by focus-floating microscopy and by a Borrelia-specific polymerase chain reaction (PCR). RESULTS: Besides a miscellaneous group of annular disorders at times confused with EAC such as urticaria, leucocytoclastic vasculitis and psoriasis (20 of 90; 22%), EAC appeared to serve as a collective term for three main clinicopathological reaction patterns: (i) (tumid) lupus erythematosus (29 of 90; 32%), (ii) spongiotic dermatitides (25 of 90; 28%) and (iii) pseudolymphoma (16 of 90; 18%). In 13 of 16 (81%) cases with a pseudolymphomatous reaction pattern spirochaetes stained positive but were negative in other reaction patterns of EAC as well as in negative controls. These findings were confirmed by a Borrelia-specific PCR which was positive in two of three (67%) of these pseudolymphomatous EAC cases but was negative in all other variants of EAC (none of five) as well as 20 controls. CONCLUSIONS: We conclude that 'EAC' is a clinical reaction pattern that does not represent a specific clinicopathological entity and should lead to consideration of mainly lupus erythematosus, dermatitis and, in some cases, cutaneous Lyme disease.

Lymphocytic infiltration of the skin (Jessner-Kanof) but not reticular erythematous mucinosis occasionally represents clinical manifestations of Borrelia-associated pseudolymphoma.

BACKGROUND: Lymphocytic infiltration of the skin (LIS) and reticular erythematous mucinosis (REM) are characterized histologically by an inflammatory cutaneous lymphocytic infiltrate similar to the histological appearance of pseudolymphoma. OBJECTIVES: To re-evaluate a large cohort of patients with the clinical and/or histological diagnosis or differential diagnosis of LIS and REM and to assess the evidence for infection with Borrelia. METHODS: Sixty-nine cases of LIS and 34 cases of REM were retrospectively investigated. Haematoxylin and eosin sections were re-examined, and histological diagnoses were specified and confirmed by clinicopathological correlation. Evidence for Borrelia infection was assessed by immunohistochemistry and focus-floating microscopy (FFM). RESULTS: LIS appeared to serve as a collective term for two main clinicopathological reaction patterns: (i) (tumid) lupus erythematosus (LE) (32 of 69, 46%) and (ii) pseudolymphoma (31 of 69, 45%). Other diagnoses (five of 69, 7%) included polymorphic light eruption, arthropod bite reaction, spongiotic dermatitis, drug eruption and urticaria. Spirochaetes were detected by FFM in 24 of 31 (77%) cases with a pseudolymphomatous reaction, while all nonpseudolymphomatous reactions were negative. Of the cases initially considered as REM, 21 of 34 (62%) were classified as LE, four of 34 (12%) as pseudolymphoma (three of four positive for Borrelia), and five of 34 (15%) as other diagnoses (folliculitis, morphoea, seborrhoeic dermatitis, prurigo and arthropod bite reaction). The diagnosis of Borrelia-associated pseudolymphoma was made significantly more often in those cases where LIS was considered as initial differential diagnosis than REM (P < 0.05). CONCLUSIONS: LIS and REM seem to represent clinicopathological reaction patterns. Our results confirm that, after accurate clinicopathological correlation, most cases of both conditions constitute hidden variants of LE. Furthermore, LIS, in contrast to REM, frequently comprises pseudolymphomatous reactions including borrelial lymphocytoma.

The expanding spectrum of cutaneous borreliosis.

The known spectrum of skin manifestations in cutaneous Lyme disease is continuously expanding and can not be regarded as completed. Besides the classical manifestations of cutaneous borreliosis like erythema (chronicum) migrans, borrelial lymphocytoma and acrodermatitis chronica atrophicans evidence is growing that at least in part also other skin manifestations, especially morphea, lichen sclerosus and cases of cutaneous B-cell lymphoma are causally related to infections with Borrelia. Also granuloma annulare and interstitial granulomatous dermatitis might be partly caused by Borrelia burgdorferi or similar strains. There are also single reports of other skin manifestations to be associated with borrelial infections like cutaneous sarcoidosis, necrobiosis lipoidica and necrobiotic xanthogranuloma. In addition, as the modern chameleon of dermatology, cutaneous borreliosis, especially borrelial lymphocytoma, mimics other skin conditions, as has been shown for erythema annulare centrifugum or lymphocytic infiltration (Jessner Kanof) of the skin.

Detection of spirochaetal microorganisms by focus floating microscopy in necrobiosis lipoidica in patients from central Europe.

AIMS: Necrobiosis lipoidica (NL) is a chronic inflammatory skin disease with unknown aetiology. The aim was to determine the presence of spirochaetal microorganisms in NL. METHODS AND RESULTS: Focus-floating microscopy (FFM) is a modified immunohistochemical technique that was developed to detect borrelial spirochaetes within tissue sections. It has proven to be more sensitive for the detection of spirochaetes than polymerase chain reaction (PCR). Fifty-six cases of NL as well as 44 negative and 33 positive controls were investigated for the presence of Borrelia within tissue specimens. Using FFM, Borrelia could be detected in 42 cases (75.0%) and were seen significantly more often in histologically active inflammatory-rich (38/41, 92.7%) than in inflammatory-poor (4/15, 26.7%) cases of NL (P < 0.001). Seven cases investigated with a Borrelia-specific PCR (23s-RNA) remained negative. In contrast, FFM was positive in 30 of 33 (90.9%) positive controls of acrodermatitis chronica atrophicans and 15 of the positive controls (45.5%) were also positive with PCR, whereas no negative controls revealed any microorganisms. CONCLUSIONS: Detection of spirochaetes in NL points to a specific involvement of B. burgdorferi or other similar strains in the development of or trigger for this disease.