In Geneva, on Saturday, the sessions attended by our roving doctor- reporters have been proving extremely popular. Both of our reporters have emphasized the high quality of the speakers, whose expertise and excellent talks have won the unanimous praise of the participants – week-end or no week-end!
Professor Tennstedt, for instance, points out that the session on nail diseases proved so popular that there was standing-room only! You’ll find his report here. Meanwhile, Professor Yordanova chose the session on mucous membrane disorders and capillary diseases of inflammatory origin. She also gives us the latest news concerning early results from a clinical study currently underway, on the use of a BTK inhibitor to treat pemphigus.
Prof. Dominique TENNSTEDT, MD, PhD
Dermatologist, Department of Dermatology UCL Saint Luc, Brussels, Belgium
This session on nail diseases was extremely popular and many members of the audience were unable to find a seat, but this did not prevent them from staying anyway, so fascinated were they by the speakers and their amazing illustrations!
Two topics that impact the daily practice of many clinical dermatologists have been selected.
Onychoscopy has become a discipline in its own right and is a crucial tool in helping clinicians to fine tune their clinical diagnoses and hence treat many patients suffering from a variety of nail disorders.
For superficial disorders, the onychoscopy is performed dry, while if discolouration is present, or the nail folds are involved, a gel is used. It can be performed on all areas of the nail unit (from the hyponychium to the nail matrix as well as for examining nail folds).
Onychoscopy makes differential diagnosis of the various nail disorders much easier and it is particularly useful for accurate diagnosis of onycholyses (traumatic, idiopathic, medication related, subungual tumour related, psoriatic, etc.).
For example, onychoscopy of a traumatic onycholysis reveals a regular, rounded border, a whitish colour, absence of subungual hyperkeratosis, and the presence of micro suffusions at the free border. Psoriatic onycholysis has an irregular, "toothed" edge, a whitish colour to the detached area, a yellowish orange colour to the attached border, the presence of filiform haemorrhages and sometimes minor sublingual hyperkeratotic formations. Mycotic onycholysis displays an irregular border with indentations that that extend beyond the onycholytic area, a yellowish orange colour that looks like an aurora borealis and subungual hyperkeratotic accumulations.
Onychoscopy can make it much easier to detect the exact nature of a subungual or periungual tumour: differential diagnosis between Bowen’s disease and a common wart, a subungual jonctional naevus and a melanoma in situ, or a pilomatricoma and an onychopapilloma, etc.
Onychoscopy can also help clinicians choose the best place to perform a biopsy.
Nail colour can help diagnosis in cases of melanonychia and yellow nail syndrome, while greenish nails suggest pyocianin infection...and let us not forget that a micro-Hutchinson sign can only be detected with a dermascope!
PSORIATIC NAIL DISEASE: WHAT CAN BE DONE, HOW CAN IT BE TREATED?
1. General measures:
- Keep nails short.
- Avoid manicures.
- Avoid injuries and infections.
- Do not listen to what friends or family tell you!
- Take no notice of advice from internet forums!
- Discourage patients from trying ‘home’ remedies or "miracle" remedies or ‘bizarre’ cures and diets.
- Explain that it is difficult to predict how psoriasis will develop and recurrences are often inevitable.
2. Topical treatments:
- Topical steroids, with or without occlusion
- Local steroid injections (to the nail matrix)
- Local MTX injections (but this slows nail growth)
3. Systemic medications:
- There have been very few controlled studies on this topic!
- People usually rely on their own practice and habits.
- Never offer systemic corticoids.
- MTX is a possibility but it slows nail growth!
- Cyclosporin A cannot be prescribed for more than 6 months (nephrotoxicity).
- The new small molecules (apremilast and tofacitinib) have not been studies much in this area but this might change.
- TNF alpha inhibitors are very effective but there is little difference between the various molecules. They might cause an increase in the frequency of onychomycoses.
- Interleukin inhibitors are also very effective. Guselkumab could turn out to be highly active even where other molecules have failed!? Exhaustion can occur after a number of years. Paradoxical psoriasis might be induced in the nail.
- Pulsed dye laser treatment works at 0.45 ms and is not too painful.
- The results are better for the nail bed than the matrix.
- Lonising radiation must not be used!
Prof. Ivelina YORDANOVA, MD, PhD
Dermatologist, Department of Dermatology and Venereology, Medical University, Pleven, Bulgaria
Dermatology of the mucosae
In the very interesting and useful afternoon session "Dermatology of the mucosae" at 16 Sep 2017 Prof. Petra De Haes from Belgium presented a lecture Special aspects of mucosal lichen planus/MLP/.
At first she explained the clinical manifestation of the disease. The oral mucous membrane is most frequently affected by MLP and the reticular subtype has a typical clinical type of MLP, usually a biopsy is not necessary to take and patients have no complaints. A rare subtype of MLP is the Plaque subtype and a biopsy is required in order to exclude malignant condition from the differential diagnosis.
The most common is the erosive subtype of MLP which is extremely painful, chronic and treatment-resisting disease which affects mainly the buccal mucous membrane.
The last subtype of MLP is very difficult for diagnosis and patients have a lot of dentist examinations for months without any effect from the treatment. A biopsy is necessary to diagnose the erosive subtype of MLP. The genital mucous membrane affection usually is presented by reticular lesions and erosions. The main differential diagnosis here is with Lichen sclerosus.
There are also other rare types MLP - esophageal, ocular, laryngeal and anal. In one patient the affection can be found in more than one mucous membrane. The strongest trigger factors for MLP are medicines: ACE inhibitors, non-steroid anti-inflammatory drugs, beta-blockers, anti-malarics, dental restoring materials /amalgama/, Hepatitis C infection.
Oral, vulvar and penile МLP are considered as premalignant conditions with potential of malignisation in SCC in 1-5,5% of the cases.
The MLP should be followed continuously and with caution for relapses or malignisation. When the lesion is suspicious for malignisation, it should be excluded by a mucous membrane biopsy. Therapeutic management of МLP is difficult. There is no curative treatment, but this is a more controllable disease. There is a standardized plan for treatment of МLP. The first line treatment is topical potent corticosteroids, topical immunomodulators - pimecrilimus and tacrolimus, additionally topical antifungal and anaestetics. If these medicines are not sufficient, we can use systemic low dose heparin /Enoxoparin/, Hydroxichloroquine, retinoids /Acitretine/.
Systemic corticosteroids should be used in short courses. If the patient is not responding to the latter, topical and systemic immunosupressors /Mycophenolat mophetyl, Cyclosporin, Methotrexate/ can be used.
Late breaking news
In the morning session on 16 Sep 2017: Late breaking news, Prof. Dr. Dedee Murrell from Australia presented the first results from an open-label Phase 2 study of the oral BTK inhibitor - PRN1008 in mild to moderate pemphigus.
Bruton’s Tyrosine Kinase (BTK) is a target for the treatment of multiple autoimmune diseases and PRN1008 was established as a potent, selective and reversible inhibitor of BTK for pemphigus. PRN1008 is a small molecule used as a monotherapy in Phase 1 clinical trial where it was tested on canine Pemphigus foliaceus for potency, durability and selectivity.
In Phase 2 clinical trial, PRN1008 was tested over human patients with mild to moderate pemphigus enrolled from 5 centers from Australia, France, Greece.
Per protocol PRN1008 was administrated orally in a dose of 400mg BID as a monotherapy from baseline to the week 12, with low dose corticosteroid - 0,5mg/kg Prednisolon at the entry of the study. As a result 43 % of the patients achieved rapid clinical response and complete remission of the disease at week 12 and the titer of Desmoglein - and Desmoglein 3-antibodies decreased dramatically in this 3 month period of treatment.
No clinical significant changes in vital signs or side effect were found, except of headache and nausea in post-treatment follow up period.
In conclusion, human B cell proliferation and activation in patients with Pemphigus vulgaris were inhibited successfully by PRN1008.
René Touraine plenary lecture
Prof. Ralf Paus who works in the field of the hair follicule diseases in the University of Manchester United Kingdom presented a brilliant plenary René Touraine lecture on the topic: Update on inflammatory hair diseases: Alopecia areata and Lichen planopilaris.
Prof. Paus explained that the hair-follicle bulge has recently been added to a growing list of human tissue compartments that exhibit a complex combination of immunosuppressive mechanisms, termed immune privilege (IP), which seem to restrict immune-mediated injury in specific locations.
As epithelial hair-follicle stem cells (eHFSC) reside in the hair-follicle bulge region, it is conceivable that these IP mechanisms protect this vital compartment from immune-mediated damage, thereby ensuring the ongoing growth and cyclic regeneration of the hair follicle.
Primary cicatricial alopecias are a group of inflammatory hair disorders that result in hair-follicle destruction and permanent alopecia.
Growing evidence suggests that eHFSC destruction is a key factor in the permanent follicle loss seen in these conditions.
Lichen planopilaris (LPP) is a chronic inflammatory disease of unknown pathogenesis that leads to permanent hair loss. In LPP bulge IP collapses because of chronic inflammation and CD8+T cells kill hair follicule stem cells. This is a Th1-type cytotoxic T cells response. Bulge destruction by inflammatory cell infiltration leads to hair follicule destruction and permanent alopecia. These novel findings raise the possibility that LPP represents an autoimmune disease in whose pathogenesis bulge IP collapse plays an important role. Therapeutically bulge IP protection and restoration may help to better manage this highly treatment-resistant cicatricial alopecia.
Alopecia areata (AA) represent a CD8+T cell–mediated, organ-speciﬁc autoimmune disease. It was proposed that a collapse of the physiological IP of anagen hair follicules is a crucial element of AA pathogenesis.
Today, this concept is well-supported by experimental and clinical evidence. Namely, although the disease cannot be transferred by hair follicule autoantibodies, the transfer of CD8+T cells alone, which recognize MHC class I–presented autoantigens, suffices to induce AA lesions.
This novel hypothesis of AA pathobiology has important clinical implications: autoantigen- and T cell specificity as well as selective gene targeting in future AA would then be much less important for effective AA management than suppressing this general, stereotypic HF response pattern to IP collapse–inducing inflammatory stimuli that we currently know under the name of ‘‘AA’’.
The disease progression may best be halted by nonspecific but effective ‘‘response pattern suppression’’, whereas disease remission and hair regrowth may mainly call for ‘‘Hair follicule IP restoration’’ therapy by JAC inhibitors, F506, Apremilast and other.