Histamine Production Research Articles

Recycling salmon meat by decontamination under mild conditions using high-pressure carbon dioxide

The 2011–2016 reports from the Food and Agriculture Organization of the United Nations has stated that annual food loss and waste occurs on a massive scale in fisheries and aquaculture. This study aimed to explore advanced technologies to recycle wasted salmon as an industrial resource with high commercial value by applying enzymatic hydrolysis under HPCD. Our results showed that HPCD treatment at 50 °C and 1 MPa for 16 h effectively prevents salmon from microbial contamination. Real-time PCR analysis demonstrated that HPCD was also able to inhibit an increase in bacteria at moderate temperatures. Based on NGS analysis, there was a very low abundance of Bacillus and some histamine producers, such as Pseudomonas, Acinetobacter, Enterobacter, and Klebsiella, detected in samples treated using HPCD at 50 °C and 1 MPa for 16 h. Hydrolysate analysis showed that HPCD treatment at 1 MPa did not affect the hydrolysates from salmon. It is anticipated that the results from this study will support the application of HPCD in industrial enzymatic hydrolysis and increase the sustainability of bio-based materials.

Assessment of the Distribution and Safety of Tetragenococcus muriaticus for Potential Application in the Preparation of Chinese Grasshopper Sub Shrimp Paste.

The bacterial profiles of 63 grasshopper sub shrimp paste samples collected from seven typical regions around the Bohai Sea were investigated by high-throughput sequencing. Tetragenococcus muriaticus was found to be the prevailing species present in all the samples, and the presence of T. muriaticus also weakly correlated with the histamine content in the samples. Six T. muriaticus strains with low biogenic amine (BA)-producing ability and deficient in histamine production were identified and subjected to safety assessment. All six strains displayed weak resistance to fifteen known antibiotics as based on the Enterococcus breakpoint values. None of the strains exhibited hemolytic activity or biofilm formation. All strains exhibited were able to grow on MRS agar containing 21% NaCl and expressed amine oxidase and strain-specific proteases and lipases. Most of the strains exhibited acid production at 18% NaCl. Moreover, three of the strains (designated as SG, TS, and QH) with histamine degradation ability were inoculated into separate shrimp paste samples to determine their effect on BA accumulation. The results indicated that the addition of T. muriaticus to shrimp pastes not only led to a significant reduction of BA content in the pastes but also improved the flavor of the pastes. Consequently, these strains may be used as potential candidates for controlling the content of histamine in fermented foods.

Research Note: Anti-inflammatory effects and antiviral activities of baicalein and chlorogenic acid against infectious bursal disease virus in embryonic eggs

The purpose of this study was to investigate if baicalein and chlorogenic acid could inhibit the inflammatory responses induced by and protect against infectious bursal disease virus (IBDV) in chicken embryonic eggs. Nine-day-old embryonated chicken eggs were randomly divided into 3 groups of 50 eggs per group: 1) treatment with varying concentrations of baicalein, 2) treatment with varying concentrations of chlorogenic acid, or 3) left untreated as a control. Forty-eight hours after hatching, each group was inoculated with a very virulent IBDV isolate, and the survival of the embryo was monitored daily until the embryonic livers were collected 72 h after inoculation. After IBDV infection, the viral loads in the embryonic livers were evaluated using qRT-PCR, and the hepatic content of inflammatory mediators, such as histamine, interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), and nuclear factor-kappa B (NF-κB), were examined. Significant antiviral potential was demonstrated at concentrations of 108 and 215 μg/egg of baicalein and chlorogenic acid, respectively. We observed a concentration-dependent response in the antiviral properties of these chemicals. Treating the embryos with baicalein and chlorogenic acid significantly reduced histamine production. Moreover, pretreatment with baicalein and chlorogenic acid significantly inhibited NF-κB activation, and this inhibited the subsequent production of the proinflammatory cytokines TNF-α and IL-1β in the context of IBDV infection. These findings suggest that baicalein and chlorogenic acid have anti-IBDV properties, and they may be useful in the prevention of inflammation-related diseases.

Effect of seafood storage temperature on histamine production and changes in free histidine

Effect of seafood storage temperature on histamine production and changes in free histidine

Autochthonous Oenococcus oeni Strain to Avoid Histamine Formation in Red Wines: A Study in Real Winemaking Conditions

The production of wines with low biogenic amine (BA) concentrations is a current concern in the wine sector, and strategies to avoid the formation of BAs during winemaking are of particular interest. The aim of this work was to determine the influence of selected autochthonous Oenococcus oeni lactic acid bacteria (LAB) on the BA content in red wines and their prevalence against the indigenous microbiota to avoid BA formation. Sixty-seven red wines were produced at industrial scale under real winemaking conditions for three consecutive vintages. For each wine, we determined LAB implantation and the BA concentrations at various stages of the winemaking process. The results clearly indicated that the use of selected O. oeni strains that are unable to produce BA, in combination with adapted biomass production, is a good strategy to control histamine production in wines. These practices, carried out over three consecutive years, were also observed to ensure the persistence of the selected autochthonous O. oeni strain (CECT 9749) against other indigenous microbiota in the entire winery. Furthermore, analysis of BA content during wine aging in barrels indicated that low BA content was maintained, resulting in healthier wines for the consumer.

The antimicrobial properties and biogenic amine production of lactic acid bacteria isolated from various fermented food products

Lactic acid bacteria (LAB) have been isolated from fermented foodstuff and pre-identified using API 50 CHL and confirmed by polymerase chain reaction method to investigate the protective properties against important foodborne pathogens of their cell-free supernatants (CFS) and neutralized cell-free supernatants (NCFS). The antimicrobial activity of CFS and NCFS was determined using agar well diffusion assay. Biogenic amine production of LAB strains were also monitored in tyrosine decarboxylase broth (TDB). The highest and lowest histamine production were obtained by Pediococcus pentosaceus (155.66 mg/L) and Lactobacillus plantarum (5.96 mg/L), respectively. CFS obtained from LAB isolates showed better antimicrobial effects against pathogens than NCFS. The CFS and NCFS obtained from L. plantarum showed a high antimicrobial effect against S. Paratyphi A with inhibition zone diameter 22.5 and 16.5 mm, respectively. The CFS and NCFS of L. raffinolactis showed strong antibacterial activities against Listeria monocytogenes, with zone diameter 23.5 and 24.5 mm. Practical applications Antimicrobial activity of cell-free and neutralized cell-free supernatants obtained from LAB strains was evaluated. Biogenic amine production of LAB strains were also monitored in tyrosine decarboxylase broth. All LAB isolates had the capacity to produce biogenic amines. Cell-free supernatants obtained from LAB isolates showed better antimicrobial effect against pathogens than neutralized cell-free supernatants. Our results showed that cell-free supernatants can be used as a bio-protective agent in the food industry.

Pharmacokinetic properties of inhibitors to Histidine Decarboxylase isolated from fennel

Histamine release is involved in developing wakefulness and activation of cortex. The purpose of the study was to find an alternative to these antihistamines by inhibiting the enzyme histidine decarboxylase which is responsible for the production of histamine. Histamine brings about the allergic response due to mast cell degranulation. It is also necessary that the enzyme is not completely inhibited as it plays a role as a neurotransmitter and also regulates gastric acid secretion. In the present study, the methanolic extract of commercially available fennel seeds were examined for its inhibitory activity on the purified extract of bacterial histidine decarboxylase. The methanolic extract of fennel was analyzed to check the presence of various phytochemical constituents. The spice extract was quantified to estimate the presence of flavonoids. The extract was subjected to purification by thin layer chromatography and HPLC in order to isolate and identify the flavonoids present in spice extract. The HPLC results with reference to the standard indicated the presence of ellagic acid and quercetin. The spice extracts were subjected to inhibitory studies at increasing concentrations. The fennel extract at concentration of 0.625 moles was found to be inhibiting histidine decarboxylase which was determined using the Dixon plot. The identified flavonoids were then subjected to software’s like Molinspiration and Swiss ADME in order to study the molecular properties, drug likeliness and pharmacokinetics.

Search for Substances That Inhibit Histamine Production Using Used Tea Leaves

As food waste has become a major problem in recent years, measures against food loss have become an urgent issue. When manufacturing or making green tea beverages, large quantities of tea leaves are subsequently disposed of, which results in potential food loss. Moreover, because many of the tea components remain in the used tea leaves, these continue to have value, as these leaves exhibit antibacterial action. Furthermore, histamine is produced from histidine via histidine decarboxylase that is produced by microorganisms, with histamine accumulation potentially causing histamine food poisoning. Although we have been trying to develop a simple method for detecting histamine, there has yet to be a quick detection method established. We examined whether a method using a low concentration of bromocresol indicator in the culture medium was capable of rapidly detecting histamine. Our results demonstrated that when using lower indicator concentrations, there was a faster detection of histamine production, within 4 h. Using this method, we also investigated whether used tea leaf components, which have antibacterial effects, could suppress histamine production. In this study, used leaves from green, oolong, and black teas were analyzed according to different extraction processes. Compared with green tea, oolong and black teas were able to suppress histamine production using lower concentrations, 25 and 12.5% extracts, respectively. In contrast, the inhibitory effect on histamine production by used green tea leaves required a high concentration of 50% used tea leaf extracts. Furthermore, our results suggested that used tea leaves suppress histamine production and that the inhibitory effects vary according to different extracts. Based on these findings, we propose that (i) a more rapid detection method for histamine should be established and (ii) used tea leaf extracts may have applications in the storage and processing of foods associated with an undesirable production of histamine.

Histamine-dependent interactions between mast cells, glia, and neurons are altered following early-life adversity in mice and humans.

Early-life adversity contributes to the development of functional bowel disorders later in life through unresolved mechanisms. Here, we tested the hypothesis that early-life adversity alters anatomical and functional interactions between mast cells and enteric glia. The effects of early-life stress were studied using the neonatal maternal separation (NMS) stress mouse model. Anatomical relationships between mast cells and enteric glia were assessed using immunohistochemistry and mast cell reporter mice (Mcpt5Cre;GCaMP5g-tdT). Immunohistochemistry was used to assess the expression of histamine, histamine 1 (H1) receptors, and glial fibrillary acidic protein. Functional responses of glia to mast cell mediators were assessed in calcium imaging experiments using Sox10CreERT2;GCaMP5g-tdT mice and cultured human enteric glial cells. NMS increases mast cell numbers at the level of the myenteric plexus and their proximity to myenteric ganglia. Myenteric glia respond to mediators released by activated mast cells that are blocked by H1 receptor antagonists in mice and humans and by blocking neuronal activity with tetrodotoxin in mouse tissue. Histamine replicates the effects of mast cell supernatants on enteric glia, and NMS increases histamine production by mast cells. NMS reduces glial responses to mast cell mediators in mouse tissue, while potentiating responses in cultured human enteric glia. NMS increases myenteric glial fibrillary acidic protein expression and reduces glial process length but does not cause neurodegeneration. Histamine receptor expression is not altered by NMS and is localized to neurons in mice, but glia in humans. Early-life stress increases the potential for interactions between enteric glia and mast cells, and histamine is a potential mediator of mast cell-glial interactions through H1 receptors. We propose that glial-mast cell signaling is a mechanism that contributes to enteric neuroplasticity driven by early-life adversity.NEW & NOTEWORTHY Early-life adversity places an individual at risk for developing functional gastrointestinal disorders later in life through unknown mechanisms. Here, we show that interactions between mast cells and glia are disrupted by early-life stress in mice and that histamine is a potential mediator of mast cell-glial interactions.

Effect and mechanism of thyme microcapsules on histamine production by Morganella morganii MN483274 during the processing of smoked horse meat sausage

In this work, we evaluated the effects of thyme microcapsules on histamine accumulation by Morganella morganii both in pure culture and during the smoked horsemeat sausage-making process. To assess the expression of histidine decarboxylase (HDC) pathway-related genes, Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was adopted. Further, relative parameters such as histamine concentration, microbiological growth, and pH were evaluated. Results revealed that thyme microcapsules inhibited the growth of M. morganii, and significantly (P < 0.05) reduced histamine accumulation by inhibiting the expression of histidine decarboxylase (hdcA) and histidine/histamine antiporter (hdcP) genes. However, it had minimal influence on the expression of the histidyl-tRNA synthetase (hdcRS) and hdcB genes in HDC clusters. Thyme microcapsules exhibited markedly higher (P < 0.05) inhibitory potential than thyme essential oil. Hence, thyme microcapsules should be added in the production process of traditional Chinese smoked horsemeat sausages.

Characterization of a novel enzyme from Photobacterium phosphoreum with histidine decarboxylase activity

Histamine or scombrotoxin fish poisoning is caused by ingestion of bacterially produced histamine in fish. Histamine-producing bacteria generally contain the histidine decarboxylase gene (hdc). However, some strains of Photobacterium phosphoreum are known to produce significant levels of histamine, although the hdc gene in these strains has not been recognized. The objective of this study was to investigate a previously unidentified mechanism of histamine production by P. phosphoreum. We identified a protein with histidine decarboxylase (HDC) activity comparable to activity of the pyridoxal-5-phosphate (PLP) dependent HDC from P. kishitanii and M. morganii. The newly identified protein (HDC2) in P. phosphoreum and P. kishitanii strains, was approximately 2× longer than the HDC protein from other Gram-negative bacteria and had 12% similarity to previously identified HDCs. In addition, the hdc2 gene cluster in P. phosphoreum was identical to the hdc gene cluster in P. kishitanii. HDC2 had optimal activity at 20–35 °C, at pH 4, and was not affected by 0–8% NaCl concentrations. Compared to the hdc gene from P. kishitanii, expression of the hdc2 gene was constitutive and not affected by pH or excess histidine. This newly identified protein explains possible mechanisms of histamine production in P. phosphoreum. Characterization of this protein will help in designing control measures to prevent or reduce histamine production in fish.

The effects both of cytokines and cell population in the production of histamine by activated bone marrow derived mast cells

The effects both of cytokines and cell population in the production of histamine by activated bone marrow derived mast cells

DETERMINATION OF HISTAMINE-FORMING BACTERIA, TOTAL COLIFORM AND ESCHERICHIA COLI IN FERMENTED FOODS

Fermented fishery food products have been generally sold in the local market, Thailand. These products were frequently contaminated with various microorganisms due to raw material and unhygienic production process. Determination of microbial contamination of fermented food products helps to assure safety for consumers. Therefore, the aims of the study were to determine total bacteria, total coliform, Escherichia coli and histamine producing bacteria from fermented fishery food products commercially distributed in several regions of Chumphon and Surat Thani provinces. Twenty-two samples of fermented fishery food products were randomly collected for bacterial contamination assay. All samples revealed the levels of pH and salt content in the range of 3.67-7.46 and 8.46%-29.69%, respectively. The bacterial contamination of the samples was tested by total plate count method. Determination of coliform bacteria and E. coli was examined by multiple-tube fermentation technique. Total bacteria, total coliform and E. coli of all samples were in the range of 2.15-7.54 log CFU/g, < 3-460 MPN/g and < 3-93 MPN/g, respectively. In addition, thirteen histamine-forming bacteria were found on histamine-forming bacteria isolation agar after incubation at 37°C for 4 days. Five isolates of histamine-forming bacteria named M1, M3, M9, M11, and M13 were selected to identify by molecular techniques. M1 and M3 were obtained from shrimp paste (Kapi) and M11 was obtained from fermented fish (Pla Pang Dang). They were identified as Enterobacter sp. M9 and M13 isolated from fermented fish (Pla Som and Pla Ra) were identified as Citrobacter farmeri and Staphylococcus kloosii, respectively.

Bioshell Calcium Oxide-Containing Liquids as a Sanitizer for the Reduction of Histamine Production in Raw Japanese Pilchard, Japanese Horse Mackerel, and Chub Mackerel.

Recently, there has been an increase in the number of food poisoning cases associated with histamine in food, mainly in relation to histamine in fish. Here, we investigated methods to decrease histamine levels in Japanese pilchard, Japanese horse mackerel, and chub Mackerel, stored at 10 °C using various concentrations of heated scallop bioshell calcium oxide (BiSCaO) suspension, dispersion (BiSCaO + Na2HPO4), colloidal dispersion (BiSCaO + NapolyPO4), scallop shell powder (SSP) Ca(OH)2 in pure water (PW) or saline, and BiSCaO water. BiSCaO in a high alkaline pH solution chemically decomposes histamine poorly, but the partial flocculation/precipitation of histamine was observed with 1 and 0.2 wt.% BiSCaO dispersion and BiSCaO colloidal dispersion, respectively. Cleaning fish samples with BiSCaO suspension, dispersion, colloidal dispersion, or BiSCaO water remarkably reduced histamine levels and normal bacterial flora (coliform bacteria (CF) and total viable bacterial cells (TC)) after storage for four days at 10 °C, while much higher histamine levels were observed after cleaning with saline. These results suggest that cleaning fish with BiSCaO dispersion, colloidal dispersion, or BiSCaO water can significantly reduce histamine levels through their bactericidal activity against histamine-producing bacteria.

Polymerase chain reaction for the detection of histamine-producing bacteria isolated from Taiwanese foods

It is important to develop rapid methods to detect the presence of histamine producers. In this study, the polymerase chain reaction (PCR) assay yielded a 367-bp DNA amplification fragment from histidine decarboxylase (hdc) of gram-positive bacteria using JV16HC/JV17HC primer, and 534-bp and 709-bp DNA amplification fragments from histidine decarboxylase of gram-negative bacteria using 106/107 and hdc-f/hdc-r primers, respectively. Seven gram-positive histamine-producing strains and 15 gram-negative histamine-producing strains isolated from Taiwanese foods successfully produced the PCR amplification products. The minimum levels of detection of Enterobacter aerogenes or Raoultella ornithinolytica after the PCR amplification using hdc-f/hdc-r and 106/107 primers were 105 and 106 CFU/mL in TSB broth, and 106 and 107 CFU/g in marlin homogenates, respectively. The hdc amplification using hdc-f/hdc-r primer was detected 2 h earlier than the HPLC detection of histamine in TSBH broth or marlin homogenates inoculated E. aerogenes or R. ornithinolytica. However, the detection of hdc amplification using the 106/107 primer and that of histamine by HPLC occurred at the same sampling time. Therefore, the PCR method could be easily used to detect potential histamine-producing bacteria in foods.

Survival and Histamine Production by Histamine-Forming Bacteria Exposed to Low Doses of Gamma Irradiation

Histamine poisoning occurs when fish containing high amount of histamine are consumed. Because histamine is thermally stable, control of histamine-forming bacteria in seafood is an appropriate strategy for preventing the formation of histamine. One prevention method is the use of gamma irradiation on the histamine formers. To understand the effect of gamma irradiation on the histamine-forming bacteria, laboratory isolates of the prolific histamine formers Morganella morganii, Klebsiella variicola, and Proteus vulgaris were exposed to various doses of gamma radiation in nutrient broth and tuna muscle spiked with histamine formers. None of the test bacteria survived in tuna muscle irradiated at 2.0 kGy. K. variicola was highly sensitive to gamma irradiation and was eliminated at a dose of 1.5 kGy. Histamine production also was reduced significantly as the radiation dose increased. These results suggest that gamma irradiation can effectively eliminate histamine-forming bacteria and reduce the threat of histamine poisoning from seafood.

A combination of inhibiting microglia activity and remodeling gut microenvironment suppresses the development and progression of experimental autoimmune uveitis

Noninfectious (autoimmune and immune-mediated) uveitis is an ocular inflammatory disease which can lead to blindness in severe cases. Due to the potential side effects of first-line drugs for clinical uveitis, novel drugs and targets against uveitis are still urgently needed. In the present study, using rat experimental autoimmune uveitis (EAU) model, we first found that minocycline treatment can substantially inhibit the development of EAU and improve the retinal function by suppressing the retinal microglial activation, and block the infiltration of inflammatory cells, including Th17, into the retina by decreasing the major histocompatibility complex class II (MHC II) expression in resident and infiltrating cells. Moreover, we demonstrated that minocycline treatment can remodel the gut microenvironment of EAU rats by restoring the relative abundance of Ruminococcus bromii, Streptococcus hyointestinalis, and Desulfovibrio sp. ABHU2SB and promoting a functional shift in the gut via reversing the levels of L-proline, allicin, aceturic acid, xanthine, and leukotriene B4, and especially increasing the production of propionic acid, histamine, and pantothenic acid. At last, we revealed that minocycline treatment can significantly attenuate the progression of EAU after inflammation onset, which may be explained by the role of minocycline in the remodeling of the gut microenvironment since selective elimination of retinal microglia on the later stages of EAU was shown to have little effect. These data clearly demonstrated that inhibition of microglial activation and remodeling of the gut microenvironment can suppress the development and progression of experimental autoimmune uveitis. Considering the excellent safety profile of minocycline in multiple clinical experiments, we suggest that minocycline may have therapeutic implications for clinical uveitis.

Suppression effects of aqueous and ethanolic extracts of propolis on biogenic amine production by Morganella psychrotolerans

Ethanolic and aqueous extracts of propolis (0.4 and 0.8%) were used to examine their in vitro impacts on the growth and biogenic amines (BAs) formation by Morganella psychrotolerans DSM 17886 in histidine decarboxylase (HDB) and sardine infusion decarboxylase broth (SIDB). In addition, the extracts effects were monitored in vivo on vacuum packaged sardine fillets with M. psychrotolerans at 3±1 °C for 15 days. Analysis of gas chromatography/mass spectrometry showed that quinolone and flavonoids present in propolis extracts. Aqueous extract of propolis were more effective than ethanolic extract to decrease bacterial load in HDB. The extracts considerably suppressed histamine formation in HDB, although inhibition effect was only found by propolis aqueous extract at doses of 0.4% in SIDB, with 30-fold lower histamine formation. Inhibition effects of propolis extracts on BAs production in fish meat were generally observed apart from noteworthy stimulation effect on histamine production of 0.8% ethanolic propolis extracts.

Growth Rate and Histamine Production of Klebsiella sp. CK02 Isolated from Skipjack Tuna Compared with Morganella morganii ATCC 25830 at Various Incubation Temperatures

One of an important quality parameter in tuna is the level of histamine content. The contamination of histamine in tuna is mainly due to the activity of histidine decarboxylase produced by the bacteria. A rapid growth of histamine producing bacteria is correlated with the practice of temperature abuse during handling. This study aimed to develop predictive growth modeling of two histamine-producing bacteria in the function of temperature. The growth and histamine production of Klebsiella sp. CK02 and Morganella morganii ATCC 25830 at various temperatures were measured in tryptic soy broth histidine (TSBH) and tuna fish infusion broth (TFIB) growth media. Broths were incubated at 4°C and 15°C for 7 days, and at 30°C and 40°C for 24 hours. The Baranyi and Roberts model was used with DMFit to determine primary growth kinectics, and the Ratkowsky square root model to describe bacterial growth rate as a function of temperature. Histamine production was enumerated by the apparent yield factor (pYhis/CFU) value. Growth rate increased with temperature, with a maximum rate at 40°C for Klebsiella sp. CK02 (0.740 log CFU/h) and M. morganii (0.578 log CFU/h). The Tmin for Klebsiella sp. CK02 in TFIB was -8.9°C, indicating better survival in low storage temperature, compare to M. morganii ATCC 25830. In addition, Klebsiella sp. CK02 produced a lower pYhis/CFU at 15 and 30°C compared to M. morganii ATCC 25830.

Results of Histidine (His) Supplementation in a Case of Severe Nummular Eczema (NE)

Abstract Objectives NE (coin-shaped, severely pruritic skin lesions) is an idiopathic, histologically indistinguishable form of atopic dermatitis (AD). NE is chronic, relapsing and debilitating. Treatment is limited to skin moisturizers and anti-inflammatory agents. Recurrence is common. Recent studies suggest that lack of the protein, filaggrin (FLG) and its derivative natural moisturizing factors (NMFs) play a role. Because FLG is a His-rich compound, l-His supplementation (LHS) may provide a nutritional NE option. In this report, we present a patient with severe, resistant NE who responded to LHS. Methods The patient is a 57 yo female with NE, unresponsive to topical emollients, topical and oral steroids, oral antihistamines, phototherapy, topical calcineurin inhibitors and immune modulating agents. She attempted nutritional options by eliminating food allergens (dairy, nuts, wheat, eggs) and followed an anti-inflammatory diet. Because these had only modest effects, a trial of oral LHS (8 gm/d) was begun. After 4 months on therapy NE improved significantly. Lesions diminished in size and number. The pruritus was nearly eliminated. Liver and kidney function remained normal. Results NE is a debilitating form of AD. Current therapy is essentially palliative, relying on the use of topical emollients and anti-inflammatory agents. Phototherapy and even systemic immune modulation provide only partial results. Standard nutritional approaches are generally of little value. In this case, LHS was attempted after all other options failed. LHS had a dramatic effect on the patient's NE, markedly reducing the pruritus and visibly improving the rash. The NE lesions became smaller and less numerous. LHS was well tolerated without notable adverse effects. His is an essential amino acid whose deficiency results in negative nitrogen balance, anemia and decreased histamine and carnosine production. His is a major component of FLG (∼10%). FLG degrades into NMFs which contribute to skin hydration and stratum corneum acidity. LHS is believed to increase FLG and NMF production. Conclusions LHS produced symptomatic improvement in a case of severe, treatment-resistant NE. We believe this effect was the result of increased FLG production due to LHS, with subsequent improvements in NMFs and skin hydration. LHS may be a therapeutic option for selected cases of resistant NE. Funding Sources None.