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Review article: skin complications associated with inflammatory bowel disease.

Cutaneous manifestations are well-recognized complications of Crohn's disease and ulcerative colitis. The incidence of these manifestations varies widely but, at the time of diagnosis, the mean incidence is around 10%. During the course of the disease, a great variety of skin lesions may develop, many of which are secondary to granulomatous cutaneous disease, reactive skin eruptions, nutritional deficiency and other associated conditions. The disorders that are directly related to the inflammatory process of Crohn's disease include perianal and peristomal ulcers and fistulae, metastatic Crohn's disease and oral granulomatous lesions. Histologically, the features are similar to those found in the inflamed bowel. These lesions usually respond to treatment of the underlying intestinal disease. The most common forms of reactive skin eruption are erythema nodosum and pyoderma gangrenosum. Certain subsets of patients are more susceptible to the development of erythema nodosum; in a previous report from our group, erythema nodosum was seen mainly in females, and in patients with colonic involvement and/or arthritis. This manifestation tends to occur during the first 2 years of the clinical course of the disease and may recur in approximately one-half of cases. Infliximab is highly effective in healing refractory lesions of erythema nodosum and pyoderma gangrenosum. Manifestations that are secondary to nutritional deficiency or associated conditions include acrodermatitis enteropathica, psoriasis and autoimmune disorders. For most of the cutaneous manifestations, the primary therapeutic target remains the bowel. Early aggressive therapy can minimize severe complications and maintenance treatment may prevent some devastating consequences.

Colitis, Ulcerative↗

Acquired zinc deficiency disease of skin.

Two patients, who were on long term parenteral hyperalimentation, developed skin lesions similar to those seen in acrodermatitis enteropathica. Both patients were treated with oral zinc sulphate and their skin lesions cleared completely. These patients are presented as an acquired zinc deficiency syndrome.

Female↗

Cutaneous fibroses induced by Borrelia burgdorferi.

Three cases of chronic infection with Borrelia burgdorferi are described. The patients presented with nodular or discoid fibrosis, partly in conjunction with acrodermatitis chronica atrophicans (ACA). Juxta-articular fibrotic nodules may develop within a few months of the onset of ACA. Nodular, discoid morphoea-like, and widespread cutaneous fibroses in chronic Borrelia infection may be provoked by trauma, surgery or electromagnetic radiation. They respond well to antibiotic therapy. These lesions offer an in vivo model for studying the evolution of immunologically induced fibrosis.

Adult↗

Juxta-articular fibrotic nodules in Borrelia infection--ultrastructural details of therapy-induced regression.

Juxta-articular fibrotic nodules in chronic Borrelia burgdorferi infection commonly regress rapidly under antibiotic therapy. They may therefore serve as a good in vivo model for studying the development and regression of cutaneous fibrotic processes. As shown in a typical case of acrodermatitis chronica atrophicans, this spirochete-induced fibrosis in the upper subcutis of the elbow region is histologically characterized by broad hyalinized collagen tracts interspersed with prominent perivascular lymphocytes and plasma cells. These immune cells vanish completely after 5 days of antibiotic treatment, while fibroblasts discharge matrix vesicles and form elastic fibres.

Elbow↗

A zinc-deficiency dermatitis in patients on total parenteral nutrition.

Three patients on home total parenteral nutrition utilizing a synthetic amino acid solutions developed a dermatitis consistent with acrodermatitis enteropathica after 30, 43 and 62 days of therapy. The dermatitis resolved after changing to casein hydrolysate in 2 patients and after full oral alimentation in the third. Although measured serum zinc levels were repeatedly normal to elevated in all patients, sufficient retrospective data analysis combined with literature review on this subject, clearly implicates zinc deficiency as the etiology for their dermatitis. Adequate zinc supplementation of synthetic amino acid solutions is essential in order to avoid this complication.

Adolescent↗

Chronic polyneuropathy and Lyme disease.

Infection of the peripheral nervous system with Borrelia burgdorferi can present as a cranial neuropathy or radiculopathy with cerebrospinal fluid (CSF) pleocytosis and intrathecal antibody production against B. burgdorferi, or as an asymmetric peripheral neuropathy with acrodermatitis chronica atrophicans (ACA) and normal CSF findings. According to North American studies, it can also present as a symmetric chronic polyneuropathy without ACA or other Lyme manifestations. Our purpose was to investigate the prevalence of B. burgdorferi antibodies in patients presenting with isolated chronic polyneuropathy (PN) in a European region with high incidence of Lyme disease. Sera from 209 PN patients and 247 healthy blood donors from Vest-Agder County, Norway, were examined. Borrelia burgdorferi antibodies were detected in 43 (21%) PN patients and in 45 (18%) healthy blood donors (P = 0.553). The prevalence of B. burgdorferi antibodies was similar (P = 0.311) in cryptogenic PN (24/102, 24%) and PNs of identified etiologies (19/107, 18%). PN patients with B. burgdorferi antibodies had normal spinal fluid white cell count and they did not differ clinically or electrophysiologically from PN patients without antibodies. None of 20 antibody-positive PN patients responded to antimicrobial treatment. The study shows that, in Europe, chronic distal PN without ACA or other Lyme manifestations is very rarely caused by a B. burgdorferi infection.

Anti-Infective Agents↗

Interpretation of immunoblots for Lyme borreliosis using a semiquantitative approach.

OBJECTIVE: To test the performances of new Borrelia garinii immunoblots specific for Borrelia burgdorferi sensu lato with a selected panel of sera from patients with various clinical presentations of Lyme borreliosis. METHODS: In order to establish the sensitivity and the specificity of these immunoblots, we tested serum samples obtained from patients with early- and late-stage Lyme disease (erythema migrans n=35, neuroborreliosis n=61, acrodermatitis chronica atrophicans (ACA) n=27 and arthritis n=41), from patients with diagnoses and laboratory findings associated with serologic cross-reactivity to Lyme disease (syphilis n=12, Epstein-Barr infection n=9, autoimmune markers n=29) and from blood donors residing in regions of low and medium endemicity (n=80, n=100). RESULTS: The combined sensitivity (IgG and IgM) of the tests was 90% for patients with erythema migrans, 92% for neuroborreliosis, 96% for ACA and 100% for Lyme arthritis. The specificity of the IgG immunoblot was 94%, and that of the IgM immunoblot was 97%, taking into account the prevalence of borrelia antibodies in the overall population. Interpretation of these immunoblots is based on scores allocated to different specific borrelia antigens. CONCLUSIONS: The Western blot technology is extremely useful in dissecting the immune response to borrelia infections, which develops gradually over a period of weeks to years and which involves the appearance of IgM and IgG antibodies directed against a number of borrelia-associated proteins.

Journal Article↗

The differential diagnosis of atopic dermatitis in childhood.

Atopic is the most common of the dermatitides seen in infancy and childhood, but there are numerous other diseases that can mimic the skin findings. These include seborrheic dermatitis, immunodeficiency, and psoriasis in infancy; scabies, tinea corporis infection, perioral, nummular, contact, and molluscum dermatitis in childhood. It is sometimes extremely difficult to differentiate between ichthyosis and AD, and it is also important to differentiate AD from erythrodermic conditions including acrodermatitis enteropathica, biotin deficiency, and Netherton syndrome. A rare condition in children that may mimic AD is mycosis fungoides.

Child↗

Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty-five cases.

Morphea (localized scleroderma), and lichen sclerosus et atrophicus (LSA) share common features with acrodermatitis chronica atrophicans (ACA), a known chronic form of borreliosis. These include similar histologic findings such as diffuse dermal fibrosis. These observations have led several investigators to consider the possibility of Borrelia burgdorferi (Bb) as a common etiologic factor among all of these diseases. The aim of this study is to investigate the role of Bb in the pathogenesis of morphea and LSA, by assaying for its presence in lesional skin biopsies from patients with these diseases. We utilized the nested polymerase chain reaction (PCR) technique to selectively amplify a longer segment of a Bb-specific somatic gene, on DNA from paraffin-embedded, formalin-fixed tissues. The results revealed no Bb-specific DNA sequence in 28 specimens of morphea/scleroderma and 7 of LSA with varying stages of disease. Furthermore, confirmatory Southern blot of the PCR product, resulted in similar findings. These data seriously question the role played by this spirochete in the pathogenesis of morphea and LSA, at least in the southeastern part of the USA.

Adult↗

Borrelia burgdorferi in the nervous system: the new "great imitator".

There are many obvious similarities between Lyme disease and syphilis. The major ones are their spirochetal etiology, the ability of the spirochetes to stay alive in human tissue for years, occurrence of clinical manifestations in stages, early disease in the skin and later disease in the brain, and susceptibility to antibiotic treatment. Thus, one can assume that many of the same lessons learned from the centuries of experience with syphilis will apply to Lyme disease. One of these lessons that should be constantly borne in mind is that spirochetal disease of the brain can mimic many other neurological diseases. Thus, the "effective clinician" must take special care to consider Lyme disease primarily because of the excellent response to antibiotics early in its course in relationship to some of the diseases it mimics. Lyme meningitis, occurring in the "second stage" of the disease, usually is fairly easily recognized because it occurs in the summer or early fall, often is associated with ECM or a recent history of it, and has a characteristic clinical picture of lymphocytic meningoradiculoneuritis. Many patients with Lyme meningitis or ECM have very mild symptoms, and it is likely that a large percentage of patients go undiagnosed and untreated. The frequency of progression of these patients to third-stage disease is unknown but may be quite high. This can be inferred from a similar situation in the other major late manifestation of Lyme disease: Lyme arthritis. A large number of patients present with joint involvement as their only manifestation of Lyme disease. Similarly, patients may present with symptoms of third-stage Lyme disease affecting the CNS, but they may not be recognized because of the lack of earlier stages usually associated with the disease. Thus, serology has become a very important tool for identifying patients exposed to B. burgdorferi. At the present time, serologic tests are the key to diagnosis of Lyme disease in its later stages, since, as in neurosyphilis, cultures and tests for antigen have not proven useful. Lyme arthritis and acrodermatitis atrophicans (ACA) both are associated with quite high antibody titers to the organism, while the test is understandably unreliable for identification of patients with ECM. Antibody titers in Lyme meningoradiculoneuritis are generally positive but often are not as high as those in ACA or arthritis. The antibody response in serum in CNS Lyme disease seems to be related to the presence of other manifestations; patients who have had both arthritis and CNS disease have quite high titers, while those with only CNS disease sometimes do not.(ABSTRACT TRUNCATED AT 400 WORDS)

Borrelia Infections↗

Zinc deficiency in murine milk underlies expression of the lethal milk (lm) mutation.

The inability of nursing pups to survive on milk of mice homozygous for the recessive mutation, lethal milk (lm), is correlated with a reduction in zinc levels of both milk and pup carcass. Administration of zinc to pups nursing on lmlm dams reduces the observed mortality and morbidity. It is suggested that lm alters zinc transport from maternal blood to milk and that its study may provide useful information for understanding the rare human disease, acrodermatitis enteropathica.

Animals↗

Improved immunoglobulin M serodiagnosis in Lyme borreliosis by using a mu-capture enzyme-linked immunosorbent assay with biotinylated Borrelia burgdorferi flagella.

A mu-capture enzyme-linked immunosorbent assay (ELISA) for detection of serum immunoglobulin M (IgM) antibodies to Borrelia burgdorferi by using biotinylated purified B. burgdorferi flagella was developed. The diagnostic performance of the mu-capture ELISA was compared with that of a conventional indirect ELISA. Sera from untreated patients with erythema migrans (n = 50), neuroborreliosis (n = 100), and acrodermatitis chronica atrophicans (ACA; n = 48) were investigated. The cutoff of the ELISAs was adjusted to a diagnostic specificity of 98% on the basis of examination of 200 serum specimens from healthy controls. The mu-capture ELISA increased the diagnostic sensitivity in patients with erythema migrans from 32 to 48% (P less than 0.01) and in patients with neuroborreliosis from 37 to 57% (P less than 0.001). Because of an increased signal/noise ratio, the mu-capture ELISA yielded a significantly better quantitative discrimination of individual positive measurements from the cutoff (P less than 0.001). The increased signal/noise ratio was most likely a consequence of the elimination of IgG competition for the test antigen. This may also explain why 12% of patients with ACA showed significantly increased specific IgM levels only by the mu-capture ELISA. Of patients with ACA, 27% had IgM rheumatoid factor. The mu-capture principle with a directly labeled antigen showed no interference with IgM rheumatoid factor, in contrast to the indirect ELISA. The high diagnostic performance and ease of this three-step mu-capture ELISA make it suitable for routine anti-B. burgdorferi IgM serodiagnosis.

Adolescent↗

Peptide-based OspC enzyme-linked immunosorbent assay for serodiagnosis of Lyme borreliosis.

Sera from 210 patients with Lyme borreliosis (LB) were studied by an enzyme-linked immunosorbent assay (ELISA) based on a synthetic peptide (pepC10) comprising the C-terminal 10-amino-acid residues of OspC of Borrelia burgdorferi. We found that 36.3 and 45.0% of the serum samples from patients with erythema migrans (EM) and neuroborreliosis (NB), respectively, displayed immunoglobulin M (IgM) anti-pepC10 reactivities, while these samples rarely (</=8%) displayed IgG antibody reactivities. Sera from patients with acrodermatitis chronica atrophicans did not contain anti-pepC10 antibodies. The diagnostic performance of this newly developed peptide ELISA was compared with those of an ELISA based on the full-length recombinant OspC protein (rOspC) and a commercially available ELISA based on the B. burgdorferi flagellum (Fla). The sensitivity of the IgM pepC10 ELISA was slightly lower (P < 0.04) than that of the rOspC ELISA for EM patients (36.3 versus 43.8%), while there was no difference for NB patients (45.0 versus 48.0%). However, the optical density values obtained by the pepC10 ELISA were generally higher than those obtained by the rOspC ELISA, leading to a significantly better quantitative discrimination between seropositive patients with NB and controls (P < 0.008). The specificity of the pepC10 ELISA was similar to those of the rOspC ELISA and the Fla ELISA for relevant controls including patients with syphilis and mononucleosis. Although the overall diagnostic sensitivity of the Fla ELISA was superior, 8.8 and 12.0% of the EM and NB patients, respectively, were antibody positive only by the pepC10 ELISA. Thus, use of a diagnostic test for LB based on the detection of IgM antibodies to pepC10 and Fla has increased sensitivity for the diagnosis of early LB.

Adolescent↗

Molecular typing of Borrelia burgdorferi sensu lato by randomly amplified polymorphic DNA fingerprinting analysis.

To study whether pathogenic clusters of Borrelia burgdorferi sensu lato strains occur, we typed 136 isolates, cultured from specimens from patients (n = 49) with various clinical entities and from ticks (n = 83) or dogs (n = 4) from different geographic regions, by randomly amplified polymorphic DNA (RAPD) fingerprinting with four arbitrary primers. The RAPD patterns were reproducible up to the 95% similarity level as shown in duplicate experiments. In these experiments the purified DNAs prepared on different days, from different colonies, and after various passages were used as templates. With an intergroup difference of 55%, the 136 strains could be divided into seven genetic clusters. Six clusters comprised and corresponded to the established species B. burgdorferi sensu stricto (n = 23), Borrelia garinii (n = 39), Borrelia afzelii (n = 59), Borrelia japonica (n = 1), Borrelia valaisiana (n = 12), and genomic group DN127 (n = 1). One strain from a patient with erythema migrans (EM) did not belong to any of the species or genomic groups known up to now. The RAPD types of B. burgdorferi sensu stricto, B. garinii, and B. afzelii isolates, which may give rise to human Lyme borreliosis (LB), were associated with their geographic origins. A high degree of genetic diversity was observed among the 39 B. garinii strains, and six subgroups could be recognized. One of these comprised eight isolates from patients with disseminated LB only and no tick isolates. B. afzelii strains from patients with EM or acrodermatitis chronica atrophicans were not clustered in particular branches. Our study showed that RAPD analysis is a powerful tool for discriminating different Borrelia species as well as Borrelia isolates within species.

Animals↗

Diagnostic value of PCR for detection of Borrelia burgdorferi in skin biopsy and urine samples from patients with skin borreliosis.

Skin biopsies of 36 patients with erythema migrans and acrodermatitis chronica atrophicans (ACA) before therapy and those of 8 patients after therapy were examined for Borrelia burgdorferi DNA by PCR. Skin biopsies of 27 patients with dermatological diseases other than Lyme borreliosis and those of 10 healthy persons were examined as controls. Two different primer sets targeting 23S rRNA (PCR I) and 66-kDa protein (PCR II) genes were used. PCR was performed with freshly frozen tissue (FFT) and paraffin-embedded tissue (PET). For FFT specimens of erythema migrans, 73% were positive by PCR I, 79% were positive by PCR II, and 88% were positive by combining PCR I and II. For PET specimens, PCR was less sensitive (PCR I, 44%; PCR II, 52%). For FFT specimens of ACA, PCR I was positive for two of five patients and PCR II was positive for four of five patients. B. burgdorferi was cultured from 79% of the erythema migrans specimens but not from any of the ACA lesions. Elevated B. burgdorferi antibodies were detected in sera of 74% of erythema migrans patients and 100% of ACA patients. All urine samples were negative by PCR II, whereas PCR I was positive for 27%. However, hybridization of these amplicons was negative. Sequencing of three amplicons identified nonborrelial DNA. In conclusion, urine PCR is not suitable for the diagnosis of skin borreliosis. A combination of two different primer sets achieves high sensitivity with skin biopsies. In early erythema migrans infection, culture and PCR are more sensitive than serology.

Adult↗

Rapid typing of Borrelia burgdorferi sensu lato species in specimens from patients with different manifestations of Lyme borreliosis.

To further investigate the pathogenic potential of different Borrelia burgdorferi genospecies, specimens from 27 patients with different manifestations of Lyme borreliosis were analyzed by PCR and reverse line blotting (RLB). In samples from Lyme arthritis patients, B. burgdorferi sensu stricto was predominantly identified, while in patients with neuroborreliosis or acrodermatitis, Borrelia garinii and Borrelia afzelii, respectively, were exclusively detected. The results demonstrate that PCR-RLB is a valuable tool for epidemiological and pathogenetic studies of Lyme borreliosis.

Adult↗

Symptomatic zinc deficiency in a breast-fed preterm infant.

A 2-month-old preterm boy who developed symptomatic zinc deficiency while being exclusively breast fed is described. Oral zinc supplements induced a complete remission but mucosal 65Zn uptake studies and metabolic balances conducted before and after withdrawal of the supplements excluded the diagnosis of acrodermatitis enteropathica. By age 12 months the boy was well and no longer required zinc supplements. Other possible causes of this patient's symptomatic zinc deficiency are discussed and these should be considered in the immediate and long-term management of preterm infants.

Breast Feeding↗

A 7 year survey of acute hepatitis type B.

Epidemiological and clinical features of acute symptomatic hepatitis type B were evaluated in 51 otherwise healthy children and in 13 children receiving immunosuppressive treatment for leukaemia and malignancy, who were admitted to hospital with acute hepatitis B surface antigen (HBsAg) positive hepatitis during a period of 7 years. Blood transfusions, or intimate contacts with asymptomatic HBsAg carriers or with contaminated material during repeated admission to hospital were the possible sources of infection in the immunosuppressed patients, whereas percutaneous exposure was identified as the source in a minority of non-immunosuppressed patients. Features of the acute phase of the illness differed little between the two groups of patients (acute liver failure developed in one patient with leukaemia and in two untreated children). Conversely, chronic evolution was observed in 69% of immunosuppressed patients but in only 9% of untreated children and affected only patients born to HBsAg positive mothers (two of four patients) or patients presenting with papular acrodermatitis (both patients).

Age Factors↗