Challenges in Drug Surveillance: Strengthening the Analysis of New Psychoactive Substances by Harmonizing Drug Checking Services in Proficiency Testing.

BACKGROUND: Drug checking is a proven harm reduction strategy and provides real-time information on the market of new psychoactive substances (NPS). It combines chemical analysis of samples with direct engagement with people who use drugs (PWUD), giving the ability to increase preparedness and responsiveness towards NPS. Next to that, it supports rapid identification of potential unwitting consumption. However, NPS cause a toxicological battle for the researchers, as factors such as the unpredictability and quick shift of the market complicate the detection. METHODS: To evaluate challenges posed towards drug checking services, proficiency testing was set up to evaluate existing analytical techniques and investigate the capability to correctly identify circulating NPS. Twenty blind substances, covering the most common categories of substances, were analyzed according to the existing protocols of the existing drug checking services, including several analytical methods such as gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with diode array detector (LC-DAD). RESULTS: The proficiency test scores range from 80 to 97.5% accuracy. The most common issues and errors are mainly unidentified compounds, presumably due to no up-to-date libraries, and/ or confusion between structural isomers, such as 3- and 4-chloroethcathinone, or structural analogs, such as MIPLA (N-methyl-N-isopropyl lysergamide) and LSD (D-lysergic acid diethylamide). CONCLUSIONS: The participating drug checking services have access to adequate analytical tools to provide feedback to drug users and provide up-to-date information on NPS.

The Granulated Sweetener Packet Sign.

The last two decades have seen a continuing shift from visual and tactile diagnoses in dermatology towards novel, state-of-the-art, and noninvasive instrumental technologies. Against the current tide toward replacing classical physical examinations with sophisticated high-tech ones, the present article will describe an easy-to-use and practical clinical sign to differentiate between metastases of malignant lesions and apparently benign inflamed/infected dermoid cysts. Epidermoid cysts (sometimes erroneously called "sebaceous cysts") are subcutaneous nodules containing keratin and encapsulated by an epidermoid wall. They are mobile nodules, smooth to the touch, variable in size, and most commonly located on the face, neck, and trunk. They may rupture or become infected and inflamed, red, painful, or purulent. Diagnosis is usually clear-cut, and uncomplicated cysts may not require treatment. Patients usually seek advice and request excision for esthetic or medical reasons (inflammation/infection). A 48-year-old otherwise healthy woman presented for a consultation because of a small cyst on her forehead (Figure 1). Two-finger palpation of the cyst revealed that it did not have the gelatinous fluctuant consistency of an ordinary cyst, but rather felt like a packet of granulated sweetener. The histological diagnosis of the cyst was small-to-medium-sized T-cell lymphoma. The diagnostic challenge of this case was to distinguish between metastases and an ordinary innocent-appearing cyst. The impression of a packet containing granular material upon palpitation of a cyst can be the definitive clue to detecting metastases of malignant lesions among what appear to be uncomplicated dermoid cysts. We have seen several such cases of subcutaneous nodules that turned out to be metastases of sarcomas and carcinomas, all of them with the same impression of a packet of granulated material upon palpation. We propose the term "granulated sweetener packet sign" for this diagnostic sign.

"Wolf's isotopic response": the originators speak their mind and set the record straight.

Having been the first to have introduced the concept of "isotopic response" three decades ago, we wanted to express some of our thoughts on its current application, now that more than 100 such cases have been reported in the literature. It is, of course, gratifying to read about its appropriate application, and it is our hope that others will refrain from distorting its original meaning.

Wolf's isotopic response: The first attempt to introduce the concept of vulnerable areas in dermatology.

The term isotopic response was coined in 1995(1) to describe the occurrence of a new skin disorder at the site of another, unrelated, and already healed skin disease. That publication paved the way to recognition of this phenomenon by the medical community worldwide with multiple reports describing it under a variety of conditions. The term isotopic response, however, turned out to be unsuitable for a Medline search, because it generated hundreds of references linked with radioactive isotopes. To facilitate Medline searches for this dermatologic phenomenon by avoiding unnecessarily time-consuming sifting through so many unrelated references, it was suggested that the name Wolf be added. The name Wolf's isotopic response has since been generally accepted and even included in Stedman's Illustrated Dictionary of Dermatology Eponyms. Although the concept of the isotopic response was conceived as being analogous to Köbner's isomorphic response, and despite the similarities between the two terms, the similarities are only "skin deep," and there is a major difference between the two. Isomorphic response means "the same morphology" (as that of the existing disease) and describes the appearance of the same disease at another location. The term isotopic response describes the appearance of an altogether different disease at the site of an already healed skin disease. We describe this entity and present representative clinical examples. Some problems in the definition of Wolf's isotopic response are provided, with special emphasis on its overlapping with Köbner's isomorphic response. The description of Wolf's isotopic response, which is analogous but not identical to the isomorphic response described some 120 years ago by Köbner, illustrates the contribution of morphologic findings and original ideas in keeping up with the ongoing progress in the field of dermatology.

Phacomatosis pigmento-pigmentaria: should we add a new type of phacomatosis? Fact and controversies.

There are currently five types of recognized phacomatosis pigmentovascularis plus one more, phacomatosis pigmentokeratotica, making six types altogether. Should we stop here and consider the classification as being complete? Or, do we leave room to add more types or, alternatively, lump the ones we have together and shorten the list? We present our reasons for adding one or two new types of phacomatoses to the current classification, in full recognition that it is already complicated and somewhat cumbersome. We consider that the benefits of doing so outweigh any additional strain on the already complicated classification. We expect that this might not sit well with some of our colleagues, but we are prepared to do battle.

Abnormal epidermal barrier in the pathogenesis of atopic dermatitis.

Despite the acknowledged contributions of a defective epidermal permeability barrier, dryness of the skin, and the propensity to develop secondary infections to the etiology and pathophysiology of atopic dermatitis (AD), these epidermal changes have, until recently, been assumed to reflect downstream consequences that are secondary phenomena of the primary immunologic abnormality--the historical "inside-outside" view that AD is basically an intrinsic inflammatory disease. In this review, we focused on the role of the epidermal barrier function in the pathophysiology of AD. Specifically, we presented data in support of a barrier-initiated pathogenesis of AD, ie, the "outside-inside" concept. First, we reviewed the evidence on the existence of inherited barrier abnormalities in AD. Reported studies on the possible association of mutations in the filaggrin gene (FLG) and data on human tissue kallikreins (KLKs) and AD have been addressed. We then dealt with the question of the causal link between impaired epidermal barrier and inflammation. Finally, the association between innate immune defense system and the increased avidity of Staphylococcus aureus for atopic skin was examined. Despite very convincing evidence to support the barrier-initiated pathogenesis of AD, the view that AD reflects the downstream consequences of a primary immunologic abnormality cannot be dismissed out of hand. Almost every line of evidence in support of the role of the epidermal barrier as the "driver" of the disease activity can be challenged and at least partially contradicted by opposing evidence. Until more data are available and until all the dust settles around this issue, we should take advantage of what we already know and use our knowledge for practical purposes. Deployment of specific strategies to restore the barrier function in AD means the use of moisturizers as first-line therapy.

Wolf's isotopic response.

The term "isotopic response" was coined by Wolf et al in 1995 to describe the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. When this term was found to be unsuitable for Medline searches because it generated hundreds of references that were linked with radioactive isotopes, it was changed to "Wolf's isotopic response" and eventually included as such in Stedman's Illustrated Dictionary of Dermatology Eponyms. Our search of the literature yielded 176 cases of Wolf's isotopic response. We describe this entity and present representative clinical examples. Some problems in the definition of Wolf's isotopic response are provided with special emphasis on its overlapping with the Koebner isomorphic response, a similar, but different, phenomenon. Also addressed are a number of issues associated with another term, "isotopic nonresponse," which had been introduced in analogy to the "isomorphic nonresponse" for describing the absence of an eruption at the site of another unrelated and already healed skin disease, or the sparing of the sites of another unrelated and already healed skin disease. In the spirit of the present issue, this contribution discusses only the clinical morphology and not the etiology, pathomechanism, or molecular biology of Wolf's isotopic response.

Nutrition and water: drinking eight glasses of water a day ensures proper skin hydration-myth or reality?

How-to books, beauty journals, the Internet, and the media usually recommend drinking six to eight glasses of water each day for keeping the skin hydrated, helping it look healthier, and making it less prone to wrinkles. We have found no scientific proof for this recommendation; nor is there proof, we must admit, that drinking less water does absolutely no harm. The only certainty about this issue is that, at the end of the day, we still await scientific evidence to validate what we know instinctively to be true--namely, that it is all a myth.

Phacomatosis pigmentopigmentalis: aberrant Mongolian spots and segmental café au lait macules.

We report a case of an otherwise healthy male newborn, with segmental café au lait spots on his left buttocks and left thigh down to the medial knee, in a nevoid pattern, and an aberrant Mongolian spot on the ipsilateral cheek of the buttocks in a checkerboard pattern. We propose the name phacomatosis pigmentopigmentalis in analogy to phacomatosis pigmentovascularis, and phacomatosis pigmentokeratotica.

In the pursuit of classifying severe cutaneous adverse reactions.

We suggest adding an additional type of lesion to the existing 4 types of lesions of the erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), namely "flat typical target" and call the original typical targets "raised typical target." The EM group would consist of raised typical targets and raised atypical targets, similar to the original definition, and the SJS/TEN group would consist of flat typical targets, flat atypical targets and macules with or without blisters. In our proposed modified classification (Table 1), all the lesions that are found in the EM group are raised, whereas all lesions that characterize the SJS/TEN group are flat, even though they have blisters on them.

A tattooed butterfly as a vector of atypical Mycobacteria.

We report the first case of cutaneous inoculation of atypical Mycobacteria secondary to tattooing. The diagnosis of atypical Mycobacteria infection of the skin was confirmed on the basis of the clinical and histologic appearance, the detection of acid-fast bacilli on Ziehl-Neelsen stain, and positive polymerase chain reaction. The medical complications of tattooing, which are manifold, are briefly summarized. This case emphasizes the need for federal regulation of tattooing, which is an invasive procedures associated with infectious and noninfectious complications.

Cutaneous reactions to temporary tattoos.

While allergic reactions to henna painting are extremely rare, we have witnessed an increasing number of reports of cutaneous reactions after henna tattooing, also called temporary tattooing. The reason for this lies in the contemporary composition of the paint, which contains paraphenylenediamine (PPD). We present six patients who developed allergic contact dermatitis after skin painting with "black henna", and who showed hypersensitivity to PPD. We discuss the issue of the short sensitization period of our patients and the reported ones.

Cafe au lait has hue of its own.

Segmental pigmentation disorder is a pigmentation disorder (hypo- or hyperpigmentation) first described some 20 years ago. It appears early in life, is segmental, and usually has a sharp border in the midline. It can be confused clinically and histologically with several pigmentary disorders, especially with giant or segmental cafe-au-lait macules. The purpose of this article is to promote, revive, and refresh this somewhat neglected entity, and to further subdivide it into two types: segmental pigmentation disorder simplex and segmental cafe-au-lait. We illustrate our contention with case reports.