Portable negative‐pressure wound therapy for pyoderma gangrenosum: Report of two cases

Pyoderma gangrenosum is a chronic non‐infectious neutrophilic dermatosis that causes undermining ulcers. Topical therapies for the deep ulcers of pyoderma gangrenosum have not been established. To investigate whether negative‐pressure wound therapy is effective for a pyoderma gangrenosum ulcer, we used the PICO single use negative‐pressure wound therapy system (Smith & Nephew, London, UK) for two pyoderma gangrenosum patients. In these cases, the ulcers decreased in size and necrolytic tissue was removed notably. Moreover, there were no secondary infections nor was there Koebner phenomena. Our cases suggest that portable negative‐pressure wound therapy can be a treatment option for deep, intractable ulcers caused by pyoderma gangrenosum. Because portable negative‐pressure wound therapy devices afford increased mobility to patients, they can give the patient a better quality of life than standard negative‐pressure wound therapy systems do.     

Drug‐induced pyoderma gangrenosum: a model to understand the pathogenesis of pyoderma gangrenosum

Pyoderma gangrenosum (PG) is a rare autoinflammatory condition in which the alteration of neutrophil function and the innate immune response play key roles in its pathogenesis. Cases of PG have been reported in patients being treated with certain medications, which may help us to understand some of the possible pathways involved in the aetiology of PG. The aim of this review is to review the cases of PG triggered by certain drugs and try to thoroughly understand the pathogenesis of the disease. To accomplish this, a PubMed search was completed using the following words: pyoderma gangrenosum, neutrophilic dermatosis, pathophysiology, drug‐induced pyoderma gangrenosum. In total, we found 43 cases of drug‐induced PG. Most of them were caused by colony‐stimulating factors and small‐molecule tyrosine kinase inhibitors. We propose that drugs induce PG through various mechanisms such as dysfunctional neutrophil migration and function, dysregulated inflammatory response, promotion of keratinocyte apoptosis and alteration of epigenetic mechanisms. PG is a rare condition with complex pathophysiology and drug‐induced cases are even more scarce; this is the main limitation of this review. Understanding the possible mechanisms of drug‐induced PG, via abnormal neutrophil migration and function, abnormal inflammation, keratinocyte apoptosis and alteration of epigenetic mechanisms would help to better understand the pathogenesis of PG and ultimately to optimize targeted therapy.     

Reacciones cutáneas adversas a medicamentos: cómo identificar el desencadenante

It is estimated that 10% to 15% of medicated patients develop adverse drug reactions (ADR). Despite the high prevalence of ADR, the identification of the trigger drugs remains a medical challenge, mainly in polymedicated patients. Our goal is to update the diagnostic tools to identify enhancer drugs of type B-ADR that compromise the skin and /or mucous membranes, in order to optimize patients’ follow-up and improve their quality of life. We develop the review in two stages: I- we review the pathophysiological mechanisms of the ADR; II- we developed the clinical approach for the identification of the triggering drug.     

Analysis of patients with drug‐induced pemphigoid using the Japanese Adverse Drug Event Report database

To clarify the incidence of drug‐induced pemphigoid in Japan, we conducted a database search and analysis using the Japanese Adverse Drug Event Report database (JADER). Among the cases recorded in JADER between April 2004 and November 2017, we targeted “pemphigoid” and analyzed the patients’ backgrounds, drug involvement, time of pemphigoid onset, outcomes and year reported. For cases where three or more drugs were reportedly involved, the signal index was calculated using the reporting odds ratio (ROR) method. The total number of reported pemphigoid cases was 769. Males accounted for 58% (446 cases) and patients over the age of 60 years accounted for 82% (630 cases). The most frequently reported causative drug was vildagliptin (288 cases), followed in order by sitagliptin phosphate hydrate (102 cases), teneligliptin hydrobromide hydrate (86 cases), linagliptin (64 cases) and furosemide (46 cases). For the 27 causative drugs, the safety signal was detected by the ROR method. The median time to onset tended to be long for these drugs. For vildagliptin with the largest reported number, the value was 508 days (range, 2–1871). Analysis of outcomes demonstrated recovery or improvement in 66.3% of cases. Analysis of the years in which reports had been published revealed that the number of pemphigoid cases has increased rapidly in recent years. Our survey was able to reveal useful data on the incidence of drug‐induced pemphigoid. We expect that these results will aid the early detection and treatment of this condition.     

Polypoid granulation tissue in pressure ulcers: Significance of describing individual ulcers

Granulation tissue formation is required for the healing of deep pressure ulcers. The wound healing process is often delayed at the stage of granulation tissue formation. The pathogenesis of pressure ulcers showing granulation tissue may vary; however, no terminology has been defined to describe existing ulcers. Thus, we previously defined terminology for granulation tissue to describe individual ulcers. Based on these terms, we retrospectively evaluated the findings of deep pressure ulcers. In particular, we focused on polypoid granular tissue, a unique morphological feature. Polypoid granulation tissues were frequently observed in pressure ulcers over the sacrum compared with those over the foot. Chronological observation of a few cases indicated that external forces from specific directions during the healing process caused the development of polypoid granulation tissue. In addition, most pressure ulcers showing polypoid granulation tissue exhibited a trench-like appearance in individual wounds. Based on these observations, polypoid granulation tissue may generate from specific external forces, which lead to wound deformity. Morphological findings in an individual wound may be useful to predict the mechanical factors on existing pressure ulcers.     

Drug‐induced systemic lupus erythematosus in a child after 3 years of treatment with carbamazepine

Drug‐induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50–70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low‐risk drug and very few cases have been reported in children. We describe the case of CBZ‐induced SLE in a 9‐year‐old girl following 3 years of CBZ therapy. This case report shows that drug‐induced SLE is an important side‐effect to be considered, even after long‐term treatment with CBZ, and also during childhood.     

Genital pyoderma gangrenosum: Report of two cases and published work review of Japanese cases

Pyoderma gangrenosum is an ulcerative skin disorder showing characteristic non‐infectious ulcers and affects the lower extremities in approximately 70% of cases. Pyoderma gangrenosum is commonly associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis and hematological malignancies. Herein, we report two cases of Japanese patients diagnosed with genital pyoderma gangrenosum. Case 1 was a 74‐year‐old woman without associated systemic complications, whose skin lesion resembled a squamous cell carcinoma and was limited to the vulva. Case 2 is an 89‐year‐old man, who suffered from myelodysplastic syndrome and acute myeloid leukemia, and presented with penile and leg ulcers mimicking pressure sores. Both cases responded well to systemic steroids. We review 13 genital pyoderma gangrenosum cases (76.9% male; aged 30–89 years) from 1996 to 2012 in Japan, including 11 previously reported cases and the present study's two cases. Four of the 13 genital pyoderma gangrenosum cases had associated systemic diseases and their skin lesions spread to the extragenital areas. Eight of the remaining nine genitalia‐localized pyoderma gangrenosum cases had no associated systemic diseases. In conclusion, genital pyoderma gangrenosum is rare and may be misdiagnosed. It should therefore be considered in cases of refractory genital ulcers. In addition, genitalia‐localized pyoderma gangrenosum tends to be without systemic complications.     

Adverse reactions and alleged allergy to local anesthetics: Analysis of 331 patients

The aim of this study was to determine the prevalence of true local anesthetic (LA) allergy among patients referred for suspected hypersensitivity and to describe the main characteristics of adverse drug reactions (ADR) induced by LA in our population. We retrospectively analyzed the medical files of patients referred to the Department of Dermatovenereology, University Hospital Center Rijeka, Rijeka, Croatia, for the investigation of LA hypersensitivity in the period between January 2000 and December 2012. A total of 331 patients underwent skin testing and, in cases of negative results, subcutaneous exposition to LA. In patients with suspected delayed reaction, patch test was performed. Altogether, 331 patients reported 419 independent ADR occurring during 346 procedures. Most commonly, patients reported having only one ADR, but 41 (12.4%) of them had two reactions, 14 (4.2%) had three, five (1.5%) had four and in one patient (0.3%) five ADR to LA were observed. The majority of reactions occurred during dental procedures when most commonly lidocaine and articaine were used. Local reactions were reported in 44 patients, whereas 490 general symptoms occurred during 375 independent ADR in 287 patients. The most common symptoms were cardiovascular system reactions in 89 patients (18.2%). Allergic reaction was detected in three patients (0.91%). One patient showed immediate‐type reaction to bupivacaine and two patients had a delayed‐type reaction to lidocaine. Adverse reactions to LA are common and are mostly due to their pharmacological properties and drug combinations or psychogenic origin. Allergic accidents to LA are rare.     

Cutaneous adverse drug reactions seen in a tertiary hospital in Johor,Malaysia

Background Adverse drug reactions are most commonly cutaneous in nature. Patterns of cutaneous adverse drug reactions (ADRs) and their causative drugs vary among the different populations previously studied. Objective Our aim is to determine the clinical pattern of drug eruptions and the common drugs implicated, particularly in severe cutaneous ADRs in our population. Materials and Methods This study was done by analyzing the database established for all adverse cutaneous drug reactions seen from January 2001 until December 2008. Results A total of 281 cutaneous ADRs were seen in 280 patients. The most common reaction pattern was maculopapular eruption (111 cases, 39.5%) followed by Stevens‐Johnson Syndrome (SJS: 79 cases, 28.1%), drug reaction with eosinophilia and systemic symptoms (DRESS: 19 cases, 6.8%), toxic epidermal necrolysis (TEN: 16 cases, 5.7 %), urticaria/angioedema (15 cases, 5.3%) and fixed drug eruptions (15 cases, 5.3%). Antibiotics (38.8%) and anticonvulsants (23.8%) accounted for 62.6% of the 281 cutaneous ADRs seen. Allopurinol was implicated in 39 (13.9%), carbamazepine in 29 (10.3%), phenytoin in 27 (9.6%) and cotrimoxazole in 26 (9.3%) cases. Carbamazepine, allopurinol and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 24.0%, 18.8% and 12.5% respectively of the 96 cases seen whereas DRESS was mainly caused by allopurinol (10 cases, 52.6%) and phenytoin (3 cases, 15.8%). Discussion The reaction patterns and drugs causing cutaneous ADRs in our population are similar to those seen in other countries although we have a much higher proportion of severe cutaneous ADRs probably due to referral bias, different prescribing habit and a higher prevalence of HLA‐B*1502 and HLA‐B*5801 which are genetic markers for carbamazepine‐induced SJS/TEN and allopurinol‐induced SJS/TEN/DRESS respectively. Conclusion The most common reaction pattern seen in our study population was maculopapular eruptions. Antibiotics, anticonvulsants and NSAIDs were the most frequently implicated drug groups. Carbamazepine and allopurinol were the two main causative drugs of severe ADRs in our population.     

Intractable genital ulcers from herpes simplex virus reactivation in drug‐induced hypersensitivity syndrome caused by allopurinol

Background Drug‐induced hypersensitivity syndrome (DIHS/DRESS) is a severe adverse systemic reaction. Reactivation of human herpesvirus (HHV) family members other than HHV‐6 has been reported in patients with DIHS. Reactivation of HHV family members is generally characterized by increased serum antibody titers against the virus. By contrast, clinical symptoms caused by viral reactivation are relatively rare. Method We report a case of DIHS with intractable genital ulcers from reactivation of herpes simplex virus (HSV) in accordance with reactivation of HHV‐6 and cytomegalovirus (CMV). Result Twenty‐two days after the onset of the rash, the patient developed intractable genital ulcers that were resistant to treatment. Histological examination of the ulcers revealed necrotic degeneration in the epidermal cells, with giant cells containing inclusion bodies and marked lymphocytic infiltration in the upper dermis. Immunohistochemical staining with antibodies reactive to HSV or CMV showed that these giant cells were positive for HSV but negative for CMV. Conclusion Genital herpes is a common skin disease. However, our case was considered to be a DIHS‐associated symptom, not an accidental complication, as the symptoms were severe and resistant to treatment.     

Efalizumab‐induced thrombocytopenia: report of relapse after re‐administration

Although a reversible, sometimes severe, drug‐induced thrombocytopenia is a recognized adverse drug reaction (ADR) in patients with psoriasis treated with efalizumab, definite proof for the association of thrombocytopenia with efalizumab is still lacking (currently level II evidence for ADR). We report a patient with psoriasis who had two episodes of reversible thrombocytopenia during efalizumab; the first occurred 5 months after introduction of the medication and the second 4 months after re‐introduction of efalizumab for relapsing psoriasis. The development of a second episode of thrombocytopenia on re‐exposure to efalizumab provides, for the first time in the literature to our knowledge, definite (level I) ADR evidence for efalizumab‐induced thrombocytopenia.     

Necrotizing soft tissue infections developing from pressure ulcers

Aim of the studyNecrotizing soft tissue infections (STIs) are serious complications that may arise from pressure ulcers. However, there are few studies on this important issue. In addition, diagnostic criteria for necrotizing STIs developing from pressure ulcers and infected pressure ulcers are not well established.MethodsWe defined necrotizing STIs developing from pressure ulcers based on clinical findings. Based on the definition, we retrospectively analyzed the medical records of 24 elderly patients with this condition to determine patient age, gender, comorbid disease, laboratory findings, wound location, bacteriology, and treatment outcomes.ResultsIn the examined population, necrotizing STIs developed primarily from pressure ulcers over the sacrum. Dementia and diabetes mellitus were also frequently observed in patients with necrotizing STIs. The average Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was relatively low. Bacterial cultures from the debrided deep tissues exhibited mixed infections of gram-positive cocci and gram-negative bacilli, except 1 case. Anaerobic pathogens were isolated from 18 patients (72%), and 7 patients (29%) developed bacteremia. None of the cases were preceded by wounds dominated by granulation tissue. Surgical intervention, combined with antibacterial therapy involving intravenous carbapenem or cephem, was successfully used in most cases.ConclusionNecrotizing STIs arising from pressure ulcers are generally caused by mixed pathogens and exhibit symptoms that are milder than those of necrotizing fasciitis caused by group A Streptococcus.     

Thalidomide-induced morbilliform rash: diagnosis and continuation of therapy,premedicated with methylprednisolone

In the past few years, thalidomide is experiencing a revival in many different fields as a last therapeutic option, because of the potential severe adverse drug reactions (ADR) induced by this drug (teratogenicity, peripheral neuropathy and sedation). Taking into consideration the increased use, we should focus on the prevalence of these and other ADR as well on their management. We describe a patient with multiple myeloma who presented with a morbilliform rash induced by thalidomide. Reintroduction of the drug confirmed the diagnosis. Nevertheless we continued the thalidomide treatment, although combined with methylprednisolone 64 mg. There was no recurrence of the cutaneous drug reaction (CDR). To the best of our knowledge, this is the first case showing that systemic steroids can help to 'treat through' a thalidomide CDR.     

Pharmacogenetics of cutaneous adverse drug reactions

Drug-induced hypersensitivity reactions are of major medical concern because they are associated with high morbidity and high mortality. In addition, individual patients' reactions are impossible to predict in each patient. In the field of severe cutaneous adverse drug reactions (cutaneous ADR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DHIS) or drug rash with eosinophilia and systemic symptoms (DRESS), major advances have recently been gained through studies of an association between HLA alleles and drug hypersensitivity induced by specific drugs. The results of these pharmacogenomic studies allow prediction of the risk of adverse reactions in patients treated with certain drugs, including carbamazepine and other aromatic antiepileptic drugs, allopurinol and abacavir. However, different ethnic populations show variations in the genetic associations. A strong association between carbamazepine-induced SJS/TEN and HLA-B*1502 has been found in Southeast Asian patients but not in Caucasian and Japanese patients. Moderate associations between aromatic amine anticonvulsants and other HLA alleles have been proposed in Japanese patients. In contrast, HLA-B*5801 was found to be associated with allopurinol-induced cutaneous ADR, including SJS/TEN and DIHS/DRESS, in Caucasian and Asian patients, including the Japanese. These differences may, at least in part, be due to the differences in allele frequency in different ethnic populations. This article reviews the progress in pharmacogenomics, associated mainly with carbamazepine and allopurinol in different ethnic populations. Pharmacogenetic screening based on associations between adverse reactions and specific HLA alleles helps to avoid serious conditions associated with drug hypersensitivity.     

Drug‐induced angioedema without urticaria: prevalence and clinical features

Background Angioedema without urticaria can be caused by drugs. The purpose of our study was to assess the prevalence and clinical features of patients with drug‐induced angioedema without urticaria. Methods This study retrospectively reviewed case records at Siriraj Hospital, between January 2007 and December 2008. Patients aged at least 15 years were included. Results The prevalence of drug‐induced angioedema without urticaria among patients with adverse drug reactions was 2.3%/year. Non‐steroidal anti‐inflammatory drugs (NSAID) were the most common cause (50%), followed by antibiotics (20%). The commonest NSAID which induced angioedema were ibuprofen and diclofenac. The common sites were periorbital area (67.3%) and lips (27.6%). The median duration of suspected drug therapy before the development of angioedema was 1 day with the range of 10 min to 23 days. Conclusions Non‐steroidal anti‐inflammatory drugs and antibiotics were the most common drugs causing angioedema without urticaria. The duration of onset ranged from minutes to days. After stopping the suspected drugs, symptoms disappeared within 2–5 days in most patients.     

Drug‐induced photosensitivity: new insights into pathomechanisms and clinical variation through basic and applied science

Drug‐induced photosensitivity occurs when a drug is capable of absorbing radiation from the sun (usually ultraviolet A) leading to chemical reactions that cause cellular damage (phototoxicity) or, more rarely, form photoallergens (photoallergy). The manifestation varies considerably in presentation and severity from mild pain to severe blistering. Despite screening strategies and guidelines in place to predict photoreactive drugs during development there are still new drugs coming onto the market that cause photosensitivity. Thus, there is a continuing need for dermatologists to be aware of the different forms of presentation and the culprit drugs. Management usually involves photoprotection and cessation of drug treatment. However, there are always cases where the culprit drug is indispensable. The reason why some patients are susceptible while others remain asymptomatic is not known. A potential mechanism for the phototoxic reactions is the generation of reactive oxygen species (ROS), and there are a number of reasons why some patients might be less able to cope with enhanced levels of ROS.     

Dermoscopic evaluation of erythema associated with pressure ulcers

Objective To assess dermoscopic findings of “non‐blanchable erythema” in stage I pressure ulcers and to determine their characteristics. Methods Dermoscopic examinations using DermLite^® II pro of redness over a bony prominence that did not resolve within 30 min of pressure relief or if a positional change was impossible for three days. Results Characteristic dermoscopic findings of redness in stage I pressure ulcers included petechial dots and telangiectatic streaks while other discolorations disappeared by diascopy. These dermoscopic features were seen in 9 of 10 cases. In one case, purpura that persisted under dermoscope compression was observed. Likewise, petechial dots and telangiectatic streaks were detected in three cases with redness surrounding stage II pressure ulcers. Conclusion The “non‐blanchable erythema” in pressure ulcers consists of petechial dots, telangiectatic streaks and purpura that persist after compression by the dermoscope and these characteristics are helpful for dermoscopically diagnosing pressure ulcers.     

Drugs associated with development of porokeratosis: A systematic review

Porokeratosis is a rare disorder characterized by atrophic macules or patches, with a well‐defined ridge‐like hyperkeratotic border called cornoid lamella. Although the exact pathogenesis is unknown, drug associated cases have recently been reported in the literature. As such, we systematically reviewed and identified drugs associated with drug‐induced porokeratosis, their resultant effects, and whether there was a casual relationship between the use of a drug and the development of porokeratosis. We searched for articles which reported drug‐induced porokeratosis in MEDLINE and Embase in June 2020. After full‐text review, 25 studies were included for analysis. We identified 26 patients with drug‐induced porokeratosis. The most common therapies associated with development of porokeratosis is biologic use, phototherapy, and radiotherapy. The most common clinical variants were the disseminated superficial or actinic types (60%), which occurred in psoriasis patients undergoing phototherapy, and eruptive disseminated type (24%) which occurred in the context of biologic therapies. The Naranjo score ranged from possible to probable for the identified treatments. Clinicians should consider drug reactions as possible triggering events for porokeratosis, especially for patients taking biologics, phototherapy, and radiotherapy. Large‐scale studies are required to confirm our findings and further explore the pathogenesis for drug‐induced porokeratosis.     

Hydrochlorothiazide‐induced photosensitivity in a psoriasis patient following exposure to narrow‐band ultraviolet B excimer therapy

Drug‐induced photosensitivity develops when the use of oral or topical photosensitizing medications creates a rash after exposure to ultraviolet (UV) radiation. Medications most commonly implicated in photosensitive drug reactions include amiodarone, nonsteroidal anti‐inflammatories, thiazides, tetracycline antibiotics, chlorpromazine, and fluoroquinolones. It is generally believed that drug‐induced photosensitivity is an UVA phenomenon, caused by UV wavelengths between 315 and 400 nm. Here, we present a case of hydrochlorothiazide (HCTZ)‐induced photosensitivity following exposure to 308‐nm narrow‐band (nb) UVB light emitted from an excimer laser in a patient undergoing treatment for plaque psoriasis. This patient had received biweekly treatments with the excimer laser for years prior without any history of adverse reactions. We believe that our patient suffered an acute photosensitivity to UVB due to new‐onset HCTZ. Because nb UVB–emitting lasers are used to treat many dermatologic conditions, physicians should be aware of potential photosensitivity reactions, review medication lists and counsel patients accordingly.