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Dermatology Online Journal is an open-access, refereed publication intended to meet reference and education needs of the international dermatology community since 1995. Dermatology Online Journal is supported by the Department of Dermatology UC Davis, and by the Northern California Veterans Administration.

Volume 19, Issue 11, 2013

Review

Urea: a comprehensive review of the clinical literature

Introduction: Urea is an organic compound that has been used clinically for dermatological diseases for more than a century. Urea is a potent emollient and keratolytic agent, making urea an effective monotherapy for conditions associated with dry and scaly skin. A systematic review of the literature is needed to provide clinicians with evidence-based applications of urea in the treatment of dermatological diseases.

Methods: A PubMed search was conducted using the term “urea” combined with “skin,” “ichthyosis,” “psoriasis,” “xerosis,” “emollient,” “onychomycosis,” “dermatitis,” and “avulsion.”  A total of 81 publications met inclusion criteria and were evaluated. Treatment indication(s), test agents, number of subjects, treatment protocols, results, and side effects were recorded.

Results: Effective treatment with urea has been reported for the following conditions: ichthyosis, xerosis, atopic dermatitis/eczema, contact dermatitis, radiation induced dermatitis, psoriasis/seborrheic dermatitis, onychomycosis, tinea pedis, keratosis, pruritus, and dystrophic nails. Furthermore, urea has been used with other medications as a penetration enhancing agent. Mild irritation is the most common adverse event, proving urea to be a safe and tolerable topical drug without systemic toxicity.

Discussion/Conclusion: Urea is a safe, effective dermatologic therapy with wide-ranging clinical utility and minimal, non-systemic side effects. In order to optimize patient care, dermatologists should be well informed with regards to urea’s indications and efficacy.

Case Report

Black spots in the returning traveler

African tick bite fever (ATBF) is a rickettsial infection that should be considered as the cause of fever in travelers returning from endemic regions of sub-Saharan Africa or the Caribbean. Patients typically present with a flu-like syndrome and may demonstrate one or more cutaneous inoculation eschars as a diagnostic key. We present a case of ATBF in a pregnant woman following her trip to Swaziland. Her symptoms rapidly improved with institution of effective antimicrobial treatment with azithromycin and rifampin; she made a full recovery.

Sporotrichoid chromomycosis

Chromomycosis is a chronic fungal skin infection. It manifests frequently by warty or vegetative lesions in exposed areas, most often secondary to trauma. The diagnosis, nevertheless, is confirmed by the presence of fungi in the mycological examination. In fact, the treatment remains a challenge given its recalcitrant nature.

First reported case of cellulitis due to Cryptococcus gattii in lung transplantation recipient: a case report.

Cryptococcus gattii are closely related species of encapsulated yeast-like fungi involved in the etiology of cryptococcosis, especially in immunocompetent individuals. Dissemination with involvement of many organ systems is common. On the other hand, cellulitis in an immunossupressed patient caused by C. gattii is rare. We present a case of disseminated disease caused by Cryptococcus gattii in a lung transplant recipient who manifested cellulitis. The disease was also complicated by a lung carcinoma. We emphasize that cryptococcal cellulitis related to C. gattii in solid organ transplant (SOT) recipients should be considered in the differential diagnosis of acute bacterial skin infections.

Case Presentation

Stasis Dermatitis as a Complication of Recurrent Levofloxacin-Associated Bilateral Leg Edema

Introduction: Several drugs have been associated with the development of peripheral edema. Leg edema can result in dermatitis of the lower extremities.  We describe levofloxacin-induced peripheral leg edema, which progressed to stasis dermatitis.

Methods: A 76-year-old man with a history of esophageal adenocarcinoma was administered intravenous vancomycin and a combination of piperacillin and tazobactam by injection for treatment of aspiration pneumonia.  Prior to discharge, the patient's antibiotic therapy was switched to oral levofloxacin.  The patient developed drug-associated bilateral peripheral leg edema and stasis dermatitis. Both the dermatitis and leg edema resolved after withdrawal of levofloxacin and administration of topical corticosteroid therapy. The patient had a similar reaction to levofloxacin one year prior, which had subsided with discontinuation of the drug.

Results: Several medications have been documented to cause leg edema and secondary stasis dermatitis.  The timing, recurrence, and resolution of edema and stasis dermatitis with respect to the administration and termination of levofloxacin suggest that the leg edema and stasis dermatitis occurred secondary to levofloxacin administration.

Discussions: Levofloxacin can be added to the list of drugs associated with the development of peripheral leg edema.   Stasis dermatitis proceeded by lower extremity edema can be added to the list of adverse events associated with levofloxacin

Granuloma annulare mimicking multicentric reticulohistiocytosis

We describe a patient with granuloma annulare (GA) who presented with firm periungual papules mimicking “coral beads”, a characteristic sign of multicentric reticulohistiocytosis (MRH).  We highlight the importance of distinguishing between GA and MRH because the prognoses differ significantly.

Facial actinic lichen nitidus successfully treated with hydroxychloroquin: a case report

Introduction : Lichen nitidus  is an unusual condition with chronic evolution. It arises as multiple tiny, shiny papules with a flat surface. Many clinical variants have been reported. We describe a new case of facial actinic lichen nitidus. Our patient responded rapidly to corticosteroids and hydroxychloroquine.

Case report: A 23-year-old woman with photodistributed eruptions recurring during the summer with improvement during the winter presented to our institution. Clinical exam revealed pinhead sized flat and flesh-colored papules on her face. Koebner phenomenon was not observed. Palms, soles, nails, and mucosa were normal. Histologic examination of a cutaneous biopsy showed a well circumscribed lymphohistiocytic infiltrate in the papillary dermis in a “claw clutching a ball” pattern suggestive of lichen nitidus. The diagnosis of actinic lichen nitidus was made. Treatment included photoprotection, topical corticosteroids once daily for 6 weeks, and hydroxychloroquine for 6 months.  Remission of lesions was obtained after 4 weeks.

Conclusion: Actinic lichen nitidus is rare. The true prevalence of this disease and the effectiveness of its various therapies is difficult to evaluate because it is usually asymptomatic and resolves without squelae.

Disseminated cutaneous sporotrichosis

The dimorphic fungus Sporothrix schenckii commonly causes localized cutaneous disease with lymphocutaneous distribution. However, disseminated sporotrichosis occurs predominantly in immunocompromised patients.  We report a case of disseminated cutaneous sporotrichosis in a patient with newly diagnosed HIV with a CD4 count of 208.  The patient presented with multiple cutaneous and subcutaneous nodules as well as fever and malaise. Tissue culture and skin biopsy confirmed the diagnosis of sporotrichosis. He was started on itraconazole 200mg twice a day with rapid resolution of fever along with cessation of the development of new lesions.

Secondary syphilis: a case mimicking erythema multiforme clinically and pathologically

Secondary syphilis, the hematogenous spread of Treponema pallidum, usually occurs 4-10 weeks after initial exposure. The skin is involved in 70% of cases, with maculopapular, vesiculobullous, and ulcerative morphologies possible at presentation, making the diagnosis of secondary syphilis challenging given its ability to mimic many other conditions. We present an atypical case of secondary syphilis that closely resembled erythema multiforme (EM) clinically and histologically

Reactive angioendotheliomatosis associated with cyroglobulinemia in a marathon runner

We report a case of a 65-year-old marathon runner who presented with painful plaques, which were worse in cold weather and  progressed to ulceration. A punch biopsy revealed vascular endothelial hyperplasia and an appearance consistent with reactive angioendotheliomatosis (RAE), a rare, but benign disorder of the skin.  Subsequent  investigations  resulted  in  the  diagnosis  of  type  I cryoglobulinemia; the  lesions  resolved  completely  following  treatment  of the underlying disorder with lenalidomide.

Recurrent migratory angioedema as cutaneous manifestation in a familiar case of TRAPS: dramatic response to Anakinra

Background: Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is a hereditary autoinflammatory syndrome characterized by recurrent episodes of fever and localized inflammation. Clinical presentation can be very variable in terms of duration of fever attacks, periodicity, and accompanying manifestations. One of the most characteristic symptoms is the occurrence of migrating skin rash with myalgia that is sustained by monocytic inflammation.

Observations: We herein present the case of a family suffering from TRAPS who had been misdiagnosed for a long period of time and whose main symptom was migrating angioedema. Skin biopsy from one of the patients documented a monocytic panniculitis. All the living patients responded dramatically to anakinra treatment.

Conclusions: The classic symptom of migratory angioedema with myalgia in TRAPS can be produced by monocytic panniculitis.This manifestation is so characteristic of TRAPS that its occurrence, even in the absence of other manifestations, should prompt genetic analysis. Our patient’s condition responded promptly to anakinra treatment.

An atypical case of cutaneous leishmaniasis caused by Leishmania infantum in Portugal

Leishmaniasis is a parasitic disease caused by an intracellular protozoan that belongs to the genus Leishmania and is transmitted by a phlebotomine sandfly. In Southwest Europe, including Portugal, cutaneous leishmaniasis is considered a rare disease of unknown or underestimated prevalence. Leishmania infantum is the only species identified as responsible for the autochthonous cases.We report the case of a 66-year-old man with an erythematous, painless plaque on the mid face region, accompanied by nasal obstruction with 9 months of evolution. The initial diagnoses were: lymphoma, subcutaneous mycosis, Wegener's granulomatosis, and lupus vulgaris. The diagnosis of leishmaniasis was based on histopathology findings and identification of L. infantum by DNA based methods. Blood cultures, abdominal ultrasound and myelogram ruled out systemic involvement. The patient was treated with intravenous meglumine antimoniate (20 mg per kg/day) for four weeks, without major side effects.We emphasize the importance of this case because human cutaneous leishmaniasis has rarely been diagnosed in Portugal and some cases are atypical, such as the situation herein described.

Cutaneous infiltratiton by chronic myelononocytic leukemia: presentation of three cases

Leukemia cutis refers to cutaneous infiltration by malignant hematopoietic cells. Its clinical manifestations are highly variable and biopsy is required for confirmation. We present three cases of patients with persistent monocytosis and skin lesions whose diagnosis was chronic myelomonocytic leukemia. The biopsy of skin lesions showed a dermal infiltration by atypical myelocytes and monocytes. Immunohistochemical study was positive for CD68. These findings were compatible with cutaneous infiltration by chronic myelomonocytic leukemic cells.

Cutaneous angiosarcoma clinically presenting as progressive solid facial edema in a 43-year-old male

Cutaneous angiosarcoma of the head and neck is a rare, highly malignant neoplasm; prognosis is heavily influenced by tumor size, resectability, and stage at initial diagnosis. Most patients present with one to several erythematous to violaceous patches, plaques, or nodules. However, the clinical presentation is highly variable and leads to delayed diagnosis. We report cutaneous angiosarcoma in a 43-year-old man who presented with an 11-month history of progressive solid (non-pitting) edema involving his entire face, scalp, eyelids, and neck without characteristic clinical features of cutaneous angiosarcoma. A skin biopsy had shown non-specific findings consistent with solid facial edema or rosacea. Various etiologies were considered but there was no significant improvement after directed medical therapy. Repeat skin biopsies revealed angiosarcoma involving the dermis and sub-cutis. Computed tomography (CT) of the chest showed multiple lung nodules bilaterally and a lytic lesion in the T6 vertebra consistent with metastases. He was treated with single agent chemotherapy (paclitaxel), and had a partial response that restored his ability to open both eyes spontaneously; However, his edema has recently progressed 7 months after diagnosis. This is a rare example of cutaneous angiosarcoma presenting as progressive solid facial edema, which underscores the diverse range of clinical manifestations associated with this neoplasm.

Letter

Photo recall reaction following the use of vancomycin

Drug-induced erythema in the distribution of prior sunburn is called photo recall.  Although more commonly induced by chemotherapeutics, it has also been associated with antibiotics such as ampicillin, cephalosporin, and gentamicin. Vancomycin has not been previously reported as a causal agent.  This case report describes photo recall in a fifty-three year old woman undergoing treatment with vancomycin for a MRSA infection of the spine. Her eruption followed a photo-distributed pattern on the chest, shoulders, neck and face sparing areas previously protected by her bathing suit. Of note, she reported a similar eruption following vancomycin two years prior.

Malignancies with skin lesions mimicking keratoacanthoma

A variety of tumors mimicking keratoacanthoma have been described. Herein we categorize metastases of visceral malignancies that can present with the appearance of a keratoacanthoma.

Editorial

Reflections on relationships between national and world events and development of dermatology. Venezuela as a model

From a personal vantage, the author tries to understand evolution of medicine and dermatology as relating to political, ideological, and economic factors.

He analyzes the evolution of Venezuelan Dermatology research and practice from 1936 to present, relating it to the events that have taken place in that country during this period and integrating the latter to events in the world. There is a close relationship between Venezuelan and US history particularly since the late nineteen-thirties.

Physicians in general and dermatologists in particular should not dismiss or just bear the events that take place in the society as a whole. They should try to influence them by acting in harmony with forces that propitiate freedom, rule of law, free inquiry, and meritocracy.

Special Review

Treatment of Hidradenitis Supprurativa Associated Pain with Nonsteroidal Anti-Inflammatory Drugs, Acetaminophen, Celecoxib, Gabapentin, Pegabalin, Duloxetine, and Venlafaxine

Hidradenitis Supprurativa is a painful dermatological condition. Although the pain of HS has unique aspects, the pain of HS pain shares common elements with essential pain, fibromyalgia, and pure neuropathic pain syndromes. Futhermore, depression plays an important role in the pain of HS. This paper reviews the potential for use of nonsteroidal anti-inflammatory drug (NSAIDS), acetaminophen, celecoxib, gabpentin, pregabalin, and the serotonin and norepinephrine reuptake inhibitors (SNRIs), duloxetine and venlafaxine, for treating HS related pain. No studies exist for pain control in HS. Initially, the pain of HS is treated medically e.g. oral rifampin and clindamycin or adalimumab to decrease inflammation, but an analysis of pain medications to treat the pain of HS merits its own discussion and treatment algorithm. First-line HS pain treatments include: topical analgesics and oral NSAIDs, such as celecoxib (Celebrex®), and acetaminophen. If these are inadequate, which is common, the less expensive gabapentin (Neurontin®) 400-1200 mg TID or the more expensive (Lyrica®) pregabalin 50-100mg BID can be added for synergistic effect. In my experience, HS patients prefer pregabalin, which induces less drowiness than gabapentin. If these combinations are inadequate, an SNRI can be added. Of SNRIs, duloxetine (Cymbalta®) 30-120 mg, given QD or divided BID, is most optimal. I have used gabapetin or pregabalin in combination with duloxtine effectively. Venlafaxine (Effexor®), 75 mg-375mg (divided into BID or TID dosing), or in extended release form Venlafaxine ER (Effexor ER®) (37.5mg-375mg daily) can be combined with pregalin or gabapetin. Venlafaxine's cardiovascular side effects and lesser effectiveness serves HS patients less well then duloxetine, in my experience. An advantage of duloxetine and venlafaxine is that they can be used to treat the depression often associated with HS. If prolonged use of opiates is required, patients should be referred to a pain specialist.