Activation of Eosinophils Interacting with Dermal Fibroblasts by Pruritogenic Cytokine IL-31 and Alarmin IL-33: Implications in Atopic Dermatitis : Dr. Wong

Activation of Eosinophils Interacting with Dermal Fibroblasts by Pruritogenic Cytokine IL-31 and Alarmin IL-33: Implications in Atopic Dermatitis.

Author Interview: Dr. CK Wong

Professor Department of Chemical Pathology
The Chinese University of Hong Kong
Prince of Wales Hospital
Shatin, NT  Hong Kong

What are the main findings of the study?

This experimental study evaluated the novel immunopathological role of pruritogenic IL-31 in conjunction with alarmin IL-33 upon the interaction of human eosinophils and dermal fibroblasts at local inflammatory sites in atopic dermatitis (AD). Our results demonstrated a stimulatory effect induced by co-culture of eosinophils and fibroblasts on cytokine and AD-related chemokines release. The above stimulatory effects could be significantly enhanced by the AD-related IL-31 and IL-33, probably via the intercellular adhesion molecule-1 cell surface expression and differential intracellular signaling mechanisms in co-culture.

Were any of the findings unexpected?

We observed the synergistic induction of AD-related chemokines in co-culture of eosinophils and dermal fibroblasts upon stimulation by IL-31 and IL-33 together.

What should clinicians and patients take away from this study?

As IL-31 and IL-33 play crucial role in AD, the circulating level of IL-31 and IL-33 may serve as specific disease markers for monitoring AD severity and therapeutic efficacy.

For AD patients, the induction of pruritogenic cytokine IL-31 may result in scratching-mediated tissue damage for the release of alarmin IL-33, these two cytokines subsequently together activate the infiltrating eosinophils interacting with dermal fibroblasts for allergic inflammation in affected skin.

What recommendations do you have for future research as a result of your study?

Future study for the IL-31 and IL-33 activating effects on skin-resident eosinophils and dermal fibroblasts obtained from AD patients is needed.

Nevertheless, our findings and established co-culture platform will facilitate the future development of selective inhibitors for cytokines and intracellular signaling molecules for the treatment of AD and inflammatory diseases.  Further animal model studies are also on-going.

Reference:

Activation of Eosinophils Interacting with Dermal Fibroblasts by Pruritogenic Cytokine IL-31 and Alarmin IL-33: Implications in Atopic Dermatitis.

Wong C-K, Leung KM-L, Qiu H-N, Chow JY-S, Choi AOK, et al.
PLoS ONE 7(1): e29815. doi:10.1371/journal.pone.0029815   (2012)

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by on January 27, 2012  •  Permalink
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Characterization of Clinical Response in Patients with Vitiligo Undergoing Autologous Epidermal Punch Grafting : Dr. Pandya

Characterization of Clinical Response in Patients with Vitiligo Undergoing Autologous Epidermal Punch Grafting

Author Interview: Amit G. Pandya, MD

Professor
Department of Dermatology
University of Texas Southwestern Medical Center
Dallas, Texas

What are the main findings of the study? 

THIS STUDY SHOWS THAT PUNCH GRAFTS:

  • ARE EASY TO DO AND RESULT IN GOOD SURVIVAL FOR MOST PATIENTS.
  • YOUNGER PATIENTS RESPOND BETTER THAN OLDER PATIENTS.
  • GRAFTING OF THE NECK AND TRUNK RESPONDS BETTER THAN ACRAL LOCATIONS AND SKIN OVER JOINTS.
  • COMPLIANCE WITH PHOTOTHERAPY WAS IMPORTANT IN ACHIEVING A GOOD RESULT.

Were any of the findings unexpected? 

WE EXPECTED THE FACE TO DO THE BEST BUT THIS WASN’T THE CASE, PERHAPS BECAUSE IT WAS A SMALL STUDY.

What should clinicians and patients take away from this study? 

PUNCH GRAFTING CAN BE DONE BY ANY DERMATOLOGIST WITHOUT VERY MUCH DIFFICULTY.

THE RESULTS ARE GOOD, ESPECIALLY FOR SMALL AREAS.

SEGMENTAL VITILIGO OF SMALL AREAS IS ESPECIALLY AMENABLE TO THIS TREATMENT.

OUR PAPER DESCRIBES HOW TO PERFORM THESE EASY GRAFTS. COBBLESTONING DOES OCCUR, BUT PATIENTS ARE USUALLY NOT BOTHERED BY IT BECAUSE THE GRAFTS ARE SO SMALL (1.5 MM). DISPOSABLE 1.5 MM PUNCHES ARE READILY AVAILABLE.

What recommendations do you have for future research as a result of your study? 

  • THE RELATIVE UTILITY OF NBUVB OVER PUVA SHOULD BE ASSESSED IN FUTURE STUDIES.
  • FUTURE STUDIES SHOULD BE PROSPECTIVE, WITH A LARGER SAMPLE SIZE IN ORDER TO OBTAIN BETTER EVIDENCE.
  • FUTURE STUDIES SHOULD ALSO INCLUDE CONTROLS AND OBJECTIVE OUTCOME MEASURES AND DETERMINE THE UTILITY OF ADJUVANT TOPICAL TREATMENTS AND PHOTOTHERAPY AFTER GRAFTING.

Reference:

Characterization of Clinical Response in Patients with Vitiligo Undergoing Autologous Epidermal Punch Grafting

Hattie Jill Feetham BS, Joanna L. Chan MD, Amit G. Pandya MD

Dermatologic Surgery
Volume 38, Issue 1, pages 14–19, January 2012
DOI: 10.1111/j.1524-4725.2011.02171.x

 

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Efficacious Treatment of Non-Dermatophyte Mould Onychomycosis with Topical Amphotericin B: Authors’ Interview

Efficacious Treatment of Non-Dermatophyte Mould Onychomycosis with Topical Amphotericin B

Authors’ Interview:

Massimo C. R. Lurati MD
Florence Baudraz-Rosselet MD
Prof. Michel Monod PhD

Private practice and Department of Dermatology
Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

What are the main findings of the study?

Dermatophytes are the main cause of onychomycosis, but a significant percentage of cases are due to various non-dermatophyte moulds especially when considering abnormal nails.

Fusarium spp. and other moulds are mostly insensitive to standard onychomycosis treatment with topical agents as well as with oral terbinafine and itraconazole (see reference 2 below).

We found that specially formulated topical amphotericin B was an efficacious, safe, cheap and easy to apply treatment for onychomycosis where non-dermatophyte moulds such as Fusarium sp., Acremonium sp. or Aspergillus sp. were the confirmed infectious agent.

Were any of the findings unexpected?

We were surprised at the speed with which healthy fungal filaments became dystrophic on direct nail smears after initiation of treatment. This is in accord with the known fungicidal mechanism of action of amphotericin B (this in contrast to the fungistatic azoles and allyamines currently in use).

What should clinicians and patients take away from this study?

Fusarium spp. and other non-dermatophyte moulds are especially difficult if not impossible to cure utilising standard treatment regimens with terbinafine and itraconazole.

It is now possible to reliably cure non-dermatophyte mould onychomycosis with topical amphotericin B. Importantly, no local or systemic side-effects are associated with this treatment.

What recommendations do you have for future research as a result of your study?

One certainly needs to further confirm the efficacy of our treatment by means of larger studies but we believe the most pressing need is for the development and widespread implementation of a rapid and practical molecular in situ fungal identification method that can be used to diagnose the etiological agent of onychomycosis before initiating treatment.

How do you identify a non-dermatophyte mould as the infectious agent in onychomycosis?

There is a suspicion of non-dermatophyte mould onychomycosis when standard empirically prescribed topical and systemic onychomycosis treatments fail.
Nowadays, different fast and reliable PCR methods of mould identification in nails are available (see references 3-5 below) and it should be standard procedure to obtain culture or PCR identification of an eventual nail pathogen before initiating any treatment. This is logical from a pharmacoeconomic point of view and a medico-legal one, the latter in case of serious treatment

References

  1. Lurati M, Baudraz-Rosselet F, Vernez M, Spring P, Bontems O, Fratti M, Monod M. Efficacious Treatment of Non-Dermatophyte Mould Onychomycosis with Topical Amphotericin B. Dermatology. 2012 Jan 10
  2. Baudraz-Rosselet F, Ruffieux C, Lurati M, Bontems O, Monod M. Onychomycosis insensitive to systemic terbinafine and azole treatments reveals non-dermatophyte moulds as infectious agents. Dermatology. 2010;220(2):164-8.
  3. Verrier J, Pronina M, Peter C, Bontems O, Fratti M, Salamin K, Schürch S, Gindro K, Wolfender JL, Harshman K, Monod M.Identification of infectious agents in onychomycoses by Polymerase Chain Reaction-Terminal Restriction Fragment Length Polymorphism. J Clin Microbiol. 2011 Dec 14. [Epub ahead of print]
  4. Bontems O, Hauser PM, Monod M. Evaluation of a polymerase chain reaction-restriction fragment length polymorphism assay for dermatophyte and nondermatophyte identification in onychomycosis. Br J Dermatol. 2009;161(4):791-6.
  5. Monod M, Bontems O, Zaugg C, Léchenne B, Fratti M, Panizzon R. Fast and reliable PCR/sequencing/RFLP assay for identification of fungi in onychomycoses. J Med Microbiol. 2006;55(Pt 9):1211-6.
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Filaggrin loss-of-function mutation R501X and 2282del4 carrier status is associated with fissured skin on the hands: results from a cross-sectional population study : Dr. Thyssen

Filaggrin loss-of-function mutation R501X and 2282del4 carrier status is associated with fissured skin on the hands: results from a cross-sectional population study

Author Interview: Dr. Jacob Pontoppidan Thyssen MD PhD

Fissured dry skin is a genetic trait

A 37-year-old female heterozygous filaggrin mutation carrier presenting with fissured skin on the dorsal aspect of the finger.

What are the main findings of the study?
We show that common loss-of-function mutations in the filaggrin gene affecting 8-10% of Northern Europeans are associated with fissured skin on the hands and fingers.

Were any of the findings unexpected?
No, we had the a priori hypothesis as we knew that the mutations in the filaggrin gene are associated with dry skin. Furthermore, we have made the clinical observation from patients seen in our clinic.

What should clinicians and patients take away from this study?
Fissured skin is indeed a genetic trait and information can be relevant.

Also, hand eczema in individuals with filaggrin mutations is characterized by dermatitis on the dorsal aspects of the hands and fingers as well as skin fissures.

What recommendations do you have for future research as a result of your study?
More studies should be conducted to describe the phenotype of patients with the filaggrin mutations.

Reference:

Filaggrin loss-of-function mutation R501X and 2282del4 carrier status is associated with fissured skin on the hands: results from a cross-sectional population study

J.P. Thyssen, K. Ross-Hansen, J.D. Johansen, C. Zachariae, B.C. Carlsen, A. Linneberg, H. Bisgaard, C.G. Carson, N.H. Nielsen, M. Meldgaard,
P.B. Szecsi, S. Stender, T. Menné

British Journal of Dermatology, 166: 46–53. doi: 10.1111/j.1365-2133.2011.10530.x

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National Psoriasis Foundation releases consensus guidelines for treatment of plaque psoriasis

PORTLAND, Ore. (January 25, 2012)—To assist the millions of Americans living with psoriasis, the most common autoimmune disease in the country, the National Psoriasis Foundation published the most recent guidelines in the United States for the management of plaque psoriasis—the most prevalent form of the disease, affecting roughly 80 percent of people with psoriasis.

Plaque Type Psoriasis of Elbow. Photo courtesy of National Psoriasis Foundation

Plaque Type Psoriasis of Elbow. Photo courtesy of National Psoriasis Foundation

The consensus guidelines from the National Psoriasis Foundation Medical Board, adapted from the Canadian Guidelines for the Management of Plaque Psoriasis to reflect U.S. practice patterns, aim to clarify when to use oral and biologic medications for people whose psoriasis is beyond topical treatment. A table summarizing the latest research and thinking on eight drugs provides data on when and how to best use them in a way that has not been done before.

“It’s a bold table in that it says directly which treatment will work or which has little evidence to support it,” said Dr. Sylvia Hsu, a member of the Psoriasis Foundation Medical Board. “It spells out clearly in one or two sentences which method is safer than we previously thought.”

One example is the recommendation that cyclosporine, an immunosuppressant drug taken orally, may be used as a short-term solution for up to 12 weeks, although FDA guidelines allow its use for up to 12 months.

The new guidelines also state that ustekinumab, commonly known as Stelara, is safe and effective as a first-line therapy. Previously, its use has been limited to second- and third-line treatment.

To view the guidelines and table, visit www.psoriasis.org/new-treatment-guidelines.

About Psoriasis

Psoriasis is the most prevalent autoimmune disease in the country, affecting as many as 7.5 million Americans. Appearing on the skin most often as red scaly patches that itch and bleed, psoriasis is chronic, painful, disfiguring and disabling. Up to 30 percent of people with psoriasis develop psoriatic arthritis, a related joint disease. There is no cure for psoriasis.

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Pressure Ulcers: Description of a New Model and Use of Mesenchymal Stem Cells for Repair

Pressure Ulcers: Description of a New Model and Use of Mesenchymal Stem Cells for Repair

Author Interview: Anabel S. de la Garza-Rodea, MD, PhD
Virus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology
Leiden University Medical Center, Einthovenweg 20
NL–2333 ZC Leiden (The Netherlands)

What are the main findings of the study?

1) Exploration and standardization of a pressure ulcer model (in mice) that present many common features as described in humans.

2) That pressure ulcers and surgical wounds respond differently to modifying influences.

Were any of the findings unexpected?

Yes, we found two surprising results. First diabetic condition in mice induced by streptozotocin did not delay the healing of the pressure ulcers. Second the participation of MSC was marginally to the repair of pressure ulcers.

What should clinicians and patients take away from this study?

New inside on wound healing cannot be applied automatically in pressure ulcers. In other words, data obtained from studies that use stem cells should be more cautious in clinical application.

What recommendations do you have for future research as a result of your study?

The pressure ulcer model described in the paper can be applied for exploration of new treatment modalities. One of these experiments would be the systemically administration of MSC to evaluate the paracrine effect of these cells.

Reference:

Pressure ulcers: description of a new model and use of mesenchymal stem cells for repair.

de la Garza-Rodea AS, Knaän-Shanzer S, van Bekkum DW.

Dermatology. 2011;223(3):266-84. Epub 2011 Nov 23.
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
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