Steven Goetze

Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention

Background: One of the most important dermatologic side effects of doxycycline is photosensitivity. As doxycycline is important for malaria prophylaxis and malaria is mainly spread in countries with high sun radiation, special attention should be paid to this adverse effect. While there are many publications on the phototoxicity of tetracyclines in general, only a few exist focusing on doxycycline. The objective of this systematic review was to summarize all available reports on clinical manifestations, influencing factors like UV dose or dose of medication, and the possibilities of prevention by sun protection. Methods: This review is based on a systematic search in PubMed for articles in English and German and a manual search between 1990 and 2015. Results: The number of publications is low. Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis. Also, onycholysis is possible. The triggering UV spectrum seems to consist mainly of UVA1 (340-400 nm), so UV-protective products should be used that cover this range. Travelers to tropical countries taking doxycycline for malaria prophylaxis need thorough medical counseling to avoid possibly severe phototoxic reactions. Conclusion: Evidence base must be improved for giving advice on appropriate prevention measures to travelers taking doxycycline and having a risk of significant sun exposure.

Isolated hyperpigmentation of the oral mucosa due to hydroxychloroquine

Hyperpigmentation of the oral mucosa is frequent in dark-skinned individuals due to physiologic deposition of melanin. In fair-skinned individuals it can represent an early sign of a systemic disease or a side effect of drug therapy. Medications that can cause such hyperpigmentation include, among others, the antimalarials such as chloroquine, hydroxychloroquine and mepacrine. A 55-year-old woman with Sjögren syndrome was presented in November 2011. She had been treated with 200 mg hydroxychloroquine (since 03/2011) and 4 mg methylprednisolone (since 10/2012). She reported asymptomatic hyperpigmentation of the oral mucosa for the past 2 months. Clinically, bluegray hyperpigmentation of the mandibular gingiva was observed (Figure 1a). The extraoral examination did not reveal any other similar pigmented lesions. Her medications included levothyroxine, pipamperone, pregabalin, escitalopram and pantoprazole. She was also using topical metronidazole for rosacea. Hyperpigmentation of the oral mucosa is not a known side effect of these medications. The patient is a long-standing smoker. Biopsy revealed a papillomatous, acanthotic broadened epithelium with distinct basal hyperpigmentation without a significant increase of melanocytes as well as isolated melanophages in the lamina propria (Figure 1b, c). Histologically, the lesions could be classified as a melanotic spot also termed a labial lentigo. We continued hydroxychloroquine because she had no retinal changes and the patient was not disturbed by the hyperpigmentation. Multiple systemic diseases such as renal insufficiency, Peutz-Jeghers syndrome, hemochromatosis, polyostotic fibrous dysplasia, hyperparathyroidism or also, for example, as a paraneoplastic change in bronchial carcinoma can lead to hyperpigmentation of the oral mucosa [1]. Our patient had none of these diseases. Likewise medication such as chemotherapeutic agents (e.g. bleomycin, cyclophosphamide, 5-fluorouracil, doxorubicin), hormones, benzodiazepines, carotenoids, phenolphthalein, amiodarone, minocycline, zidovudine, clofazimine, antimalarial agents and even heavy metals [1, 2] must be considered as possible triggers; our patient had received none of these. In addition to individual case reports, a detailed report of hyperpigmentation of the oral mucosa due to antimalarials was presented by Lippard and Kauer in 1945. The report dealt with US soldiers who had taken quinacrine for malaria prophylaxis [3]. While hyperpigmentation is often found on the hard palate, the location in the vestibulum oris, as in our patient, is rather rare. Further sites may be the shins, the face, the trunk and the nail bed [4]. Due to the location and the long-standing nicotine abuse one might suspect that the hyperpigmentation resulted from smoking, but she had been smoking for many years without any mucocutaneous complaints. Nicotine-induced hyperpigmentation is more often brown to brown-gray and is more likely found on the maxillary gingiva [5]. Treatment with hydroxychloroquine had been initiated 6–7 months ago. The interval until manifestation of hyperpigmentation due to antimalarials varies between 4 and 70 months [6]. In older publications hyperpigmentation was reported in up to 25 % of patients treated with antimalarials for more than 4 months [7]. In those times, however, higher daily doses than today were employed, possibly explaining why such hyperpigmentation is observed more rarely today. Our patient is 169 cm tall and weighs 70 kg. According to Ochsendorf [8] her ideal body weight is 58.7 kg, which would allow for a daily dose of up to 381.2 mg hydroxychloroquine without the danger of developing irreversible retinopathy. Our patient took only 200 mg hydroxychloroquine daily. After discontinuation of the medication, spontaneous regression of the hyperpigmentation is supposed to occur within 11–20 months [9]. More recent papers suggest a time period of 2–6 months [4]. Even though earlier studies postulated hemosiderin as cause of the hyperpigmentation, currently increased production of melanin is held responsible [3, 10], as is detectable in our case. As antimalarials were formerly more often employed against inflammation, the often associated bleeding secondary to inflammation led to the assumption that hemosiderin was the cause of the hyperpigmentation [3, 10]. The exact cause has not been elucidated to date. It is postulated that the antimalarials chloroquine and hydroxychloroquine directly stimulate the melanocytes [10]. Other studies have shown that chloroquine binds to melanin and that histologically detectable granules consist of a melanin-chloroquine complex [1]. Savage et al. were able to identify an indirect effect of the antimalarial agent pyrimethamine on the pigmentation of the oral mucosa in rats due to an increased plasma testosterone level and its melanotropic effect, while

Retrospective chart analysis of incidental findings detected by 18F‐fluorodeoxyglucose‐PET/CT in patients with cutaneous malignant melanoma

: 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (FDG‐PET/CT) frequently reveals incidental findings. The present study focused on incidental FDG‐PET/CT findings in cutaneous melanoma patients, and verified their relevance with respect to further diagnostic measures and interventions.

Lichturtikaria – Urticaria solaris

Die Lichturtikaria ist eine seltene, IgE‐vermittelte und von Chromophoren abhängige Photodermatose. In manchen Fällen können diese Chromophore im Serum oder Plasma der Patienten als sogenannter „Serumfaktor“ nachgewiesen werden. Die genaue Pathogenese der Lichturtikaria ist jedoch bislang ungeklärt. Typisch ist die Quaddelbildung innerhalb weniger Minuten nach Lichtexposition, welche anamnestisch schon zur Verdachtsdiagnose führt. Die häufigsten Auslöser sind UV‐A oder sichtbares Licht. Diagnostisch von Bedeutung ist die Feststellung des Aktionsspektrums und der minimalen urtikariellen Dosis (MUD). Differenzialdiagnostisch müssen andere Lichtdermatosen (wie polymorphe Lichtdermatose) oder Porphyrien (insbesondere erythropoetische Protoporphyrie) ausgeschlossen werden. Außer dem stets notwendigen Lichtschutz werden moderne Antihistaminika sowie Lichtabhärtung (hardening) therapeutisch eingesetzt. Neuere Therapieverfahren wie die Plasmapherese oder der Anti‐IgE‐Antikörper Omalizumab bleiben schweren, therapieresistenten Formen vorbehalten.

Blisters, ulcers, crusts, and atrophic scars on the back of the hands and the extensor aspects of the forearms

A 51-year-old secretary presented with a two-month history of skin lesions on the back of the hands as well as the extensor aspects of the fi ngers and forearms. She reported blisters that left poorly healing wounds covered with crusts. At the time of consultation, she was on adalimumab (40 mg every 14 days) and methotrexate (10 mg and 15 mg, alternating on a weekly basis) for rheumatoid arthritis. For the past four years, her regular antiinfl ammatory medication had also included naproxen. Topical treatment with zinc ointment had been without success.

Blasen, Ulzera, Krusten und Atrophien an Handrücken und Unterarmstreckseiten

Eine 51-jährige Sekretärin stellte sich mit seit zwei Monaten bestehenden Hautveränderungen der Handrücken sowie der Fingerund Unterarmstreckseiten vor. Sie beschrieb Blasen, welche schlecht heilende, von Krusten besetzte Wunden hinterlassen würden. Bei der Patientin war eine rheumatoide Arthritis bekannt, welche zum Konsultationszeitpunkt mit Adalimumab 14-tägig 40 mg und Methotrexat 10 und 15 mg im wöchentlichen Wechsel behandelt wurde. Als regelmäßige antiphlogistische Medikation wurde Naproxen seit zirka vier Jahren eingenommen. Lokal hatte die Patientin bereits erfolglos eine Zinksalbe angewandt. Blasen, Ulzera, Krusten und Atrophien an Handrücken und Unterarmstreckseiten Blisters, ulcers, crusts, and atrophic scars on the back of the hands and the extensor aspects of the forearms Diagnosequiz

Fulminant course of angiosarcoma of the scalp on multimodal therapy with paclitaxel, bevacizumab, and radiation: Correspondence

We report on a 65-year-old patient who presented with a nontender, ulcerated tumor on the right side of the scalp. The lesion had initially started as a small plaque three months earlier. Given the suspected diagnosis of deep trichophytosis, he had initially been treated with a broad-spectrum topical antifungal agent and subsequently with systemic antibiotics, without improvement. Upon admission, clinical examination showed a polycyclic crusted ulcer (15×10 cm) with bluish-livid, indurated margins; the lesion readily bled upon contact. In addition, the right side of the face was marked by diffuse, nontender soft tissue edema. There was no cervical lymphadenopathy. Clinically suspecting angiosarcoma or Kaposis sarcoma, a biopsy revealed epithelioid angiosarcoma, which was confi rmed by immunohistochemical staining for CD31, CD34, podoplanin, and factor XIII. A PET-CT scan and cranial MRI revealed extensive right-sided infi ltration of the galea without osseous involvement, extending across the midline. Spreading across the neck and the anterior chest wall by direct extension, the tumor involved the entire mediastinum and the adjacent parts of the diaphragm, giving rise to bilateral pleural effusions; there were no lymph node or distant metastases (Figure 1 a, b). In this palliative setting, the patient was started on paclitaxel (80 mg/m2 body surface, day 1, 8, 15) and the anti-VEGF antibody bevacizumab (10 mg/ kg body weight every other week), along with radiation therapy. Given its potential radiotoxic effects, paclitaxel was discontinued during radiation therapy. Due to symptomatic, malignant pleural effusions requiring repeated drainage, the patient underwent left-sided pleurodesis, during which pleural metastasis was histologically confi rmed. During on going treatment, the scalp and neck lesions showed signifi cant

Incidental detection of new-onset melanoma using PET-CT in a patient with stage III melanoma

Important measures in the follow-up of melanoma patients not only include clinical inspection and examination but – in patients with stage IIC and higher – also imaging studies (predominantly in the fi rst three years). Follow-up should be employed in a structured manner, based on objectives such as early detection of recurrences/metastases and secondary melanomas as well as providing patients with psychosocial support. The circumstances and results of the clinical or imaging workup for metastatic disease are primarily affected by the temporal course and disease stage [ 1 ] . The majority of recurrences and secondary melanomas are found during physical examination [ 2, 3 ] . Current S3 melanoma guidelines recommend PET-CT (positron emission tomography combined with computed tomography) for staging and follow-up in patients with stage IIC disease and higher [ 1 ] . In September 2014, a 55-year-old female patient with a history of melanoma of the right nasolabial region in March 2007 (Breslow tumor thickness of at least 8.4 mm; Clark’s level IV-V) presented – outside the scheduled follow-up visits – for evaluation of a new mass in the right submandibular region. In addition to the primary melanoma, a secondary melanoma (melanoma in situ) above the right knee had been excised in 2011. Moreover, the patient was status post breast cancer treated with left mastectomy in 2006. Apart from a previously detected lymph node (LN), which showed no signs of progression, ultrasound revealed the new mass to be a predominantly hypoechoic roundish structure measuring 15.7 × 11.8 mm; the more echogenic hilum was displaced (Figure 1 a). The aforementioned clinical fi ndings showing a mass newly arisen in the lymphatic drainage area of the primary melanoma as well as the sonographic fi ndings led to the suspected diagnosis of a lymph node metastasis. Further diagnostic workup using PET-CT and cranial MRI showed no evidence of cerebral and visceral metastases; there was, however, marked FDG uptake in the metastatic lymph node in the right submandibular region. In addition, PET-CT showed an indeterminate hypermetabolic focus in the right scapular region (Figure 1 b). Initially, the patient underwent surgery (performed by ENT specialists) of the cervical LN metastases, which included resection of the submandibular gland as well as selective right neck dissection. Pathology revealed a melanoma metastasis in one out of eleven LNs. Postoperatively, the FDG accumulation in the right scapular region on

Genitales Ulkus am Penis eines 58-jährigen HIV-positiven Patienten nach lokaler Injektion von Methamphetamin (Crystal Meth)

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Schmerzhafte Fußschwellung bei 41-jähriger Patientin.

Eine 41-jährige Patientin stellte sich mit seit elf Monaten bestehender, zuweilen schmerzhafter Schwellung beider Vorfüße mit Linksseitenbetonung in unserer Poliklinik vor. Kleine Knötchen waren tastbar, die Schmerzen insgesamt jedoch eher diffus und die Schwellungen waren nicht druckschmerzhaft. In einer Vorfußultraschalluntersuchung links wurde dorsal über dem Metatarsalgelenk I eine floride synovialitische Schwellung festgestellt. In einer Röntgenaufnahme ergab sich der Verdacht auf einen akuten Gichtanfall. Die Borrelienserologie, Antikörper gegenüber citrullinierte Peptide, cund p-ANCA und ENA waren negativ. Eine Vorbehandlung mit Ibuprofen hatte zur leichten Besserung, nicht aber zur Abheilung geführt. Schmerzhafte Fußschwellung bei 41-jähriger Patientin Painful pedal edema in a 41-year-old patient Diagnosequiz