Vitamin and trace metal levels in recessive dystrophic epidermolysis bullosa

BACKGROUND: In recessive dystrophic epidermolysis bullosa (RDEB), a good nutritional balance is necessary to obtain healing of the chronic wounds. However, involvement of the oral mucosa and oesophagus stenosis may be responsible for severe nutritional deficiencies. OBJECTIVE: In order to propose an adapted nutritional management, we studied the vitamin and trace metal status of 14 RDEB patients. METHODS: Height and weight were measured. Plasma levels of albumin, iron, ferritin, calcium, parathyroid hormone (PTH), folates, vitamins C, D, B12, A, E, B1, B6, PP and B2, zinc, selenium, carnitine and copper were measured. RESULTS: Most patients had a significant growth retardation. We found iron, vitamin D, C, B6, PP, zinc and selenium deficiencies in 36-70% of the patients, without clinical expression, except in one case. Vitamin B1, 12, B2, A/RBP, E/lipids and carnitine were normal. The three patients with gastrostomy feeding had better growth but still a protein deficiency and sometimes vitamin C, B6, PP, zinc and carnitine deficiencies. CONCLUSION: Vitamin and trace metal deficiencies are frequent in RDEB, even in patients receiving gastrostomy feeding, and often go unrecognized. Regular nutritional evaluation is necessary. Dietary advice and supplements should be given. Enteral feeding by gastrostomy should be discussed in early childhood.     

Skin reactions caused by vitamin K in patients with liver disease

Vitamin K and its analogues are frequently used in treatment of the hypoprothrombinaemia found in disease of the liver, biliary tract and small intestine. Most cases of cutaneous toxicity to vitamin K have been described in the French literature, but only two cases from Britain. This paper reports six patients with chronic liver disease who developed cutaneous reactions around the site of injection of vitamin K, and the results of investigations to futher understanding of the pathogenesis of the rash.     

Gastrointestinal investigations in dermatitis herpetiformis.

Thirty-seven patients with dermatitis herpetiformis (DH) have been investigated for gastric and small intestinal abnormalities. Evidence of an enteropathy was found in 86% of the patients who had IgA deposits in uninvolved skin. Villous atrophy of the small intestine was found in 29 patients. About one-half of the patients had reduced absorption of xylose and vitamin A. The Schilling test value was lowered in one-third. Serum B12 was too low in 5/28 patients whereas folic acid in serum and whole blood was too low in 14/29 and 5/19, respectively. Atrophic gastritis occurred in 14/28 patients and only about one-third of the whole patient material had normal gastric mucosal structure and secretion.     

低频强声对大鼠胃肠道传输功能影响的实验研究

目的探讨低频强声对大鼠胃肠道传输功能及形态学的影响。方法随机将大鼠暴露于频率103Hz或300Hz的声场中,暴露时间分别为5min或10min。根据暴露的频率、作用时间,分为4个实验组和对照组。依据暴露后观察时间,每组内再分为即刻、3d和7d三个小组。对低频强声暴露后应用炭粉混悬液法测量胃肠道食物传输功能,并对小肠进行组织病理学观察。结果低频强声暴露后胃肠道食物传输功能明显下降,暴露后不同时间点胃肠道食物传输功能存在差异,P=0．001。所有强声暴露的大鼠中,共有2例出现小肠出血,发生率约为3．7％。结论低频强声可引起大鼠胃肠道传输功能及形态改变。     

Acute generalized exanthematous pustulosis in hypercalcemia

BACKGROUND: We report a case of typical exanthematous pustulosis rash that was particularly severe both clinically and biologically. Laboratory tests led to the diagnosis of acute parvovirus B19 infection. CASE REPORT: A 23-year-old man with no past medical history developed fever with an erythematous pustulosis rash predominantly involving the folds. Blood cell count revealed hyperleukocytosis. There was no previous drug intake. This skin reaction was associated with severe systemic manifestations including hypovolemic shock, and hematologic and metabolic disturbances. Virology tests revealed acute parvovirus B19 infection. The hospital physician caring for this patient also presented evidence of acute parvovirus B19 infection. DISCUSSION: The clinical features and the course of this skin eruption were typical of generalized exanthematous pustulosis. We discuss the rare viral causes of acute generalized exanthematous pustulosis and compare our case with a previously reported case of acute generalized exanthematous pustulosis with mononucleosic syndrome in a patient with no prior drug intake. The clinical and biological manifestations of this case were similar to drug hypersensitivity syndrome.     

Newborn infant with hemophagocytic lymphohistiocytosis and generalized skin eruptions

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease resulting from abnormal proliferation of histiocytes in tissues and organs. The incidence of HLH is 1:50,000-300,000. Cutaneous eruptions have been reported in 6-65% of the cases. It's important to differentiate the eruptions from other systemic diseases. We present an infant with prominent skin manifestations of HLH. On the 11th day of life, she was admitted to our hospital with complaint of a generalized rash that had started the previous day. The eruptions consisted of irregularly shaped maculopapular erythematous rash and purpura. Bone marrow aspiration on the 25th day of life revealed hemophagocytosis with increased macrophages and histiocytes, consistent with HLH. Treatment was started with dexamethasone followed by induction chemotherapy with etoposide. All skin manifestations resolved in a few days. Although the clinical features are nonspecific, HLH should be kept in mind as an accompanying disease in neonates presenting with skin eruptions.     

The cutaneous pathology of lupus erythematosus: a review

The presentation of lupus erythematosus (LE) ranges from a skin rash unaccompanied by extracutaneous stigmata to a rapidly progressive lethal multiorgan disease. The diagnosis and subclassification is traditionally based on the correlation of serological and clinical findings. The latter include a photoinduced skin rash, arthralgia, arthritis, fever, Raynaud's phenomenon, anemia, leukopenia, serositis, nephritis and central nervous sysdtem disease. The conventional classification scheme includes systemic, subacute cutaneous and discoid LE. Recent advances in our understanding of the cutaneous histopathology which correlates with the traditional forms of LE, along with certain novel LE subtypes, are the focus of this review. In addition to the main subtypes of LE, we will discuss associated vasculopathic lesions and the contribution of immunofluorescence microscopy to the diagnosis of LE and related connective tissue disease syndromes. Consideration will be given to unusual variants of LE such as anti-Ro/SSA-positive systemic lupus erythematosus (SLE), bullous SLE, lymphomatoid LE, lupus erythematosus profundus, drug induced LE, linear cutaneous LE, chiblains LE and parvovirus B19-associated LE.     

Similarly potent action of 1,25-dihydroxyvitamin D3 and its analogues,tacalcitol, calcipotriol,and maxacalcitol on normal human keratinocyte proliferation and differentiation

BACKGROUND: The active vitamin D3 regulates proliferation and differentiation of epidermal keratinocytes. Recently topical vitamin D3, tacalcitol, calcipotriol, and maxacalcitol are widely used for psoriasis. OBJECTIVE: To examine the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on cultured normal keratinocytes (NHK) and compared its effect with those of various vitamin D3 analogues. METHODS: Cell proliferation of NHK cells was analyzed by MTS, BrdU and 3H-thymidine incorporation. The expression of involucrin, transglutaminase 1, keratin 5 and keratin 1 was investigated by western blot and PCR amplification and quantitative assay. Furthermore, we performed cornified cell envelope (CE) formation assay. RESULTS: 1,25(OH)2D3, tacalcitol, calcipotriol, and maxacalcitol decreased NHK cell proliferation in a concentration-dependent manner and the maximal effect was observed at 10(-7) M. There was no significant difference in the anti-proliferative effect among the active vitamin D3 analogues. The expression of involucrin and transglutaminase 1 were induced by 1,25(OH)2D3 and its analogues in mRNA and protein levels. CE formation was also induced by 1,25(OH)2D3 and its analogues. There was no significant difference in the potency among these chemicals. Keratin 5 and 1 expression was not altered by these active vitamin D3 analogues. CONCLUSIONS: The present study demonstrated that active vitamin D3 analogues, tacalcitol, calcipotriol, and maxacalcitol, suppress keratinocyte proliferation and induce differentiation with similar potency.     

Acne treatment with oral zinc and vitamin A: effects on the serum levels of zinc and retinol binding protein (RBP).

The serum levels of zinc, vitamin A and retinol binding protein (RBP) were studied in 75 acne patients before and during oral treatment with zinc, vitamin A or placebo. In the zinc-treated patients an increase in the mean serum zinc level was seen after 2 weeks, when also the first clinical improvement occurred. After 4 weeks the zinc level had increased by about 30% and no further significant increase was observed during 3 months of treatment. In 33 healthy subjects there was an increase of 14% after 4 weeks of zinc therapy. Vitamin A and placebo induced no significant changes in the serum zinc status. Prior to therapy the serum levels of vitamin A and RBP were lower in the acne patients than in the controls. Zinc + vitamin A treatment raised the serum RBP value to normal after 4 weeks. In patients given vitamin A alone, a probable increase in RBP was achieved. Zinc and placebo treatment did not change the serum level of RBP.     

Blood vitamin and trace metal levels in epidermolysis bullosa

Plasma or erythrocyte levels of ten nutrients (vitamins A, C, B12 and B6; folate; thiamine; riboflavin; zinc; copper; iron) were assayed in 73 patients with various forms of inherited epidermolysis bullosa (EB). Whereas the mean level for each nutrient was within its normal range, deficient levels were noted in individual EB subsets for selected nutrients. Notable abnormalities included low levels of plasma iron and zinc (in junctional EB and recessive dystrophic EB), vitamin C (primarily in EB simplex), vitamin A (in junctional and recessive dystrophic EB), vitamin B12 (primarily in EB simplex), and vitamin B6 (especially in recessive dystrophic EB). With the exception of low plasma iron and zinc levels in junctional and recessive dystrophic EB, however, only a minority of patients in any of the EB subsets had low levels of most of the other nutrients, and an apparent correlation with malabsorption was possible with only selected nutrients.     

Cutaneous manifestations of zinc deficiency in ethylic cirrhosis

Thirty-three patients with alcoholic cirrhosis (AC), selected on widely recognized criteria (16, 57), were investigated prospectively for cutaneous manifestations of zinc deficiency. The patients were divided into 3 groups: group A (n = 12): AC without skin lesions; group B (n = 12): AC with skin lesions responsive to a zinc-free topical treatment or resistant to enteral zinc sulfate intake; group C (n = 9): AC with skin lesions cured by oral zinc replacement therapy alone. The lesions observed in group C were studied microscopically. Data concerning zinc metabolism (Zn concentrations in plasma, red cells, urine and hair; alkaline phosphatase values), biochemical criteria of AC (plasma serum-albumin concentration, IgA/transferrin ratio) and a malabsorption test (xylosemia 120 min after oral absorption of D-xylose 25 g) were compared by the variance analysis method. A control group (D, n = 12) was used as reference. Few cases of cutaneous manifestations of zinc deficiency in AC patients have been published. In more than one half of the 15 or so we found in the literature, an aggravating factor (total parenteral nutrition, digestive tract surgery) had to be taken into account. In this prospective study 9 new cases in which AC was the only cause of zinc deficiency are reported. A clinical picture similar to acrodermatitis enteropathica with peribuccal bullous lesions was observed in only one patient. In all other cases the patients presented with a cracked and reticulated eczema on the extensor aspect of the limbs and (often erosive) in the perianal and genital regions. The eczema was associated with cheilitis, glossitis, stomatitis, alopecia and, seldom, ungual Beau's lines. Disorders of behaviour, diarrhoea and bouts of lever regressing under zinc replacement therapy were frequent. Histology was not very specific, except for the presence of necrotic areas in the stratum germinativum, sometimes associated with small subcorneal pustules containing altered polymorphonuclears. In every case, it was the rapid regression of symptoms under zinc sulfate treatment that confirmed the diagnosis. Plasma zinc concentrations were most significantly decreased in all AC groups as compared to controls (61.2 +/- 19.4 vs 97.8 +/- 10.4 micrograms/100 ml) and also in AC patients with skin manifestations of zinc deficiency as compared to the other AC patients (44.4 +/- 9.2 vs 66.5 +/- 18.8 micrograms/100 ml) table V). Changes in serum-albumin levels and in hepatocellular function were parallel to changes in plasma zinc concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Lupus-erythematosus-like eruption induced by Trichophyton mentagrophytes infection

BACKGROUND: Several factors are known to trigger acute manifestations of lupus erythematosus (drugs, ultraviolet radiation, bacterial or viral infections, pregnancy), but fungal infections have never been reported to induce lupus-like lesions. We describe 2 children with tinea capitis caused by Trichophyton mentagrophytes(TM), who developed transient skin and serological manifestations of systemic lupus erythematosus. PATIENTS: Case 1, a 3-year-old girl, had a kerion due to TM transmitted by an octodon, and a facial skin eruption suggestive of systemic lupus erythematosus. Antinuclear antibodies (ANA) were positive at 1:250. After griseofulvin treatment, the lupus-like rash completely regressed, and the ANA titre decreased. Case 2, a 4-year-old girl, had occipital kerion and an annular scaly erythema on the shoulder caused by TM. She also had a non-scaly rash on the face and a recent history of photosensitivity. The ANA titre was positive at 1:8,000. Cutaneous lesions disappeared after an 8-week griseofulvin therapy, and ANA titres decreased progressively. CONCLUSIONS: 'New pets' are usually the vectors of TM, especially familiar rodents like the degu of Chile (also named octodon). In our 2 cases, lupus-like rashes began before the onset of griseofulvin treatment, suggesting a pathogenic role of the dermatophyte. A wide variety of lesions named 'mycides' was described several decades ago associated with TM infections. We hypothesize that these mycides and the TM-induced lupus-like lesions reported in our 2 cases could represent the same entity.     

Local reinfusion of B10 cells is effective in the treatment of pustular psoriasis

Psoriasis is a common chronic skin disease characterized by epidermal proliferation and inflammation. Pustular psoriasis (PP) is one of the most serious and refractory. The number, differentiation, and function of B10 cells in patients with PP were analyzed, and the relationship between B10 cells and PP, an autoimmune disease, was explored. We established an Imiquimod psoriasis mouse model and subcutaneously injected B10 cells as treatment. We found that the proportion of B10 cells in the peripheral blood of patients with PP was lower than that of the normal controls. However, the number of B10 precursor cells increased. B10 cells in the peripheral blood may be mobilized to effector sites, such as the skin. In patients with PP, B10 cells do not display evident developmental disorders under the CD40 and TLR9 pathways. Normal human B10 cells were found to inhibit the secretion of IFN‐γ and TNF‐α by lymphocytes significantly. Whereas the function of B10 cells in patients with PP is impaired, and the inhibition is not apparent. Treatment with a B10 cells injection displays a certain therapeutic effect on PP. This study enriched the etiology and pathogenesis of PP. It provides a foundation for cell therapy for the treatment of autoimmune diseases.     

The alpha and beta subunits of the metalloprotease meprin are expressed in separate layers of human epidermis, revealing different functions in keratinocyte proliferation and differentiation

The zinc endopeptidase meprin (EC 3.4.24.18) is expressed in brush border membranes of intestine and kidney tubules, intestinal leukocytes, and certain cancer cells, suggesting a role in epithelial differentiation and cell migration. Here we show by RT-PCR and immunoblotting that meprin is also expressed in human skin. As visualized by immunohistochemistry, the two meprin subunits are localized in separate cell layers of the human epidermis. Meprin alpha is expressed in the stratum basale, whereas meprin beta is found in cells of the stratum granulosum just beneath the stratum corneum. In hyperproliferative epidermis such as in psoriasis vulgaris, meprin alpha showed a marked shift of expression from the basal to the uppermost layers of the epidermis. The expression patterns suggest distinct functions for the two subunits in skin. This assumption is supported by diverse effects of recombinant meprin alpha and beta on human adult low-calcium high-temperature keratinocytes. Here, beta induced a dramatic change in cell morphology and reduced the cell number, indicating a function in terminal differentiation, whereas meprin alpha did not affect cell viability, and may play a role in basal keratinocyte proliferation.     

Lupus erythematosus: systemic and cutaneous manifestations

Skin and joint involvements are the most commonly occurring manifestations of systemic lupus erythematosus. There are 3 forms of cutaneous lupus: chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. Joint manifestations are usually not associated with warmth of the joints and may be only associated with pain and swelling. Painful or swollen joints respond rapidly to small or moderate doses of corticosteroids, whereas cutaneous manifestations usually respond to antimalarial drugs. Anti-Ro is associated closely with a photosensitive rash and with subacute lupus.     

Hair zinc, scalp hair quantity, and diaper rash in normal infants

Hair zinc concentration was determined by atomic absorption spectrophotometry in 308 normal newborn infants and 199 normal infants aged one to twelve months. Hair zinc concentration declined from 204 micrograms/gm at birth to 112 micrograms/gm at age eight months, and then rose to 144 micrograms/gm at age twelve months. Diaper rash was significantly associated with reduced hair zinc, and infants with the least hair had lower zinc levels than infants with the most hair. The data indicate that hair loss and diaper rash found in normal infants is significantly associated with a reduction in hair zinc concentration.     

Long term follow-up of dermatitis herpetiformis with and without dietary gluten withdrawal

Seventy-eight patients with dermatitis herpetiformis have been followed up for periods ranging from 3 to 14 years (mean 7.4). Forty-two patients were treated with gluten-free diet (GFD) and thirty-six took a normal diet (ND). Thirty of the forty-two (71%) taking the GFD were able to discontinue drugs previously needed to control their rash compared with five (14%) of the thirty-six patients taking a ND. The mean time taken to reduce drug requirements for patients taking a GFD was 8 months (range 4–30), and for stopping drugs, 29 months (range 6–108). The incidence of macroscopic abnormality of the small intestine decreased from 69 to 15%, and the mean intra-epithelial lymphocyte count decreased significantly in those patients taking a GFD, whereas there was no significant change in patients taking a ND. The improvement in the skin and intestinal lesions was related to the strictness of the GFD.     

Dermatitis as a presenting sign of cystic fibrosis.

BACKGROUND--Three percent to 13% of patients with cystic fibrosis present with protein-energy malnutrition that is characterized by hypoproteinemia, edema, and anemia and is associated with high morbidity and mortality. Cutaneous manifestations of malnutrition are rare in patients with cystic fibrosis and have been attributed to deficiencies of protein, zinc, and essential fatty acids. OBSERVATIONS--We describe five patients who presented with failure to thrive, hypoproteinemia, edema, and a cutaneous eruption before the onset of pulmonary symptoms and before the diagnosis of cystic fibrosis was made. The rash had a predilection for the extremities (lower > upper), perineum, and periorificial surfaces. In most cases, erythematous, scaling papules developed by 4 months of age and progressed within 1 to 3 months to extensive, desquamating plaques. Alopecia was variable, and mucous membrane or nail involvement was not observed. The rash was associated with malnutrition and resolved in all survivors within 10 days of providing pancreatic enzyme and nutritional supplementation. The pathogenesis of the rash is unclear, but it appears to stem from deficiencies of zinc, protein, and essential fatty acids and may be mediated by alterations in prostaglandin metabolism. CONCLUSIONS--Cystic fibrosis should be included in the differential diagnosis of the red, scaly infant, particularly when failure to thrive, hypoproteinemia, and edema are also present. Recognition of rash as a sign of cystic fibrosis complicated by protein-energy malnutrition will allow earlier diagnosis and treatment of these patients and may improve their outcome.     

Intestinal permeability in dermatitis herpetiformis

Differential absorption of D-xylose and 3-0-methyl-D-glucose, and unmediated intestinal permeation (simple diffusion) of lactulose and L-rhamnose, have been investigated in 20 patients with dermatitis herpetiformis. Both iso-osmolar and hyperosmolar test solutions were employed and the results were compared with those obtained from a group of healthy adult volunteers. The findings in each patient have been correlated with small intestinal histology. The majority of patients with villous atrophy had abnormally raised intestinal lactulose permeation and lactulose/rhamnose permeability ratios, whereas patients with normal small intestinal morphological grading did not differ significantly from the healthy control group in this respect. There was a high incidence of delayed plasma D-xylose absorption peaks in dermatitis herpetiformis irrespective of small intestinal histological findings. These results imply that abnormal intestinal permeability in dermatitis herpetiformis is the result of gluten-induced damage to the mucosa rather than an inherent primary defect. It is therefore improbable that the rash in this condition is purely a manifestation of increased intestinal permeation of antigen.     

Mucocutaneous manifestations of HIV infection in 91 children born to HIV-seropositive women

We examined 91 children under the age of 13 years with definite HIV infection born to HIV-seropositive women. The clinical spectrum of HIV infection in children younger than 13 years who are born to HIV-infected mothers was revised in 1994 into four clinical categories: category N (not symptomatic), category A (mildly symptomatic), category B (moderately symptomatic), and category C (severely symptomatic). Mucocutaneous manifestations were found in 47 (51.6%) of these children. The prevalence of mucocutaneous manifestations in categories A, B, and C were 4%, 62%, and 75%, respectively. The mucocutaneous manifestations in patients in categories B and C were significantly more common than in those category A (p < 0.001). The most common finding was oral candidiasis (36.3%). Drug rash, pruritic papular eruption, herpes zoster, cutaneous candidiasis, Penicillium marneffei infection, and herpes simplex virus stomatitis were found in 6.6%, 5.5%, 4. 4%, 3.4%, and 2. 2% of patients, respectively. All three patients who had disseminated P. marneffei infection were in category C.