Necrotizing Sweet's syndrome: diagnosis and clinical management

Abstract The skin condition, acute febrile neutrophilic dermatosis, also commonly referred to as Sweet's Syndrome was originally reported by Dr. Robert Douglas Sweet in 1964 (Sweet, 1964). Over the course of the half-century since that initial description, there has been a growing body of scholarship concerning this disorder that has indicated there is no racial predilection but middle-aged women are most vulnerable. In addition, the research to date has also identified the most common symptoms that are experienced by sufferers, and Sweet’s syndrome is characterized by the rapid onset of neutrophilia, tender erythematous skin lesions, and fever. In the upper dermis, the disorder is characterized by a diffuse infiltrate of neutrophils histologically (Corbeddu, Pilloni, Pinna & Rongioletti, 2018). The overarching goal of this case report is to provide a review of the relevant peer-reviewed and scholarly literature concerning Sweet’s syndrome and its implications for the treatment of a 24-year-old transsexual male presenting with recurrent myonecrosis of the neck/upper chest who experienced multiple hospitalizations. This goal will serve to increase awareness of necrotizing Sweet's syndrome in ways that will facilitate its early diagnosis and efficacious treatment. This goal is also consistent with research to date that stresses the need for early diagnosis of Sweet’s syndrome in order to reduce associated morbidity by avoiding unneeded surgical interventions that may be harmful and delay appropriate treatment. The findings that emerge from this research indicate that clinicians should consider necrotizing Sweet's syndrome for all patients that present with the symptoms of necrotizing soft-tissue infections that is characterized by difficulty in resolution together with individuals that remain body fluid and/or tissue culture-negative (Otero et al., 2017).
Key Words:
Acute febrile neutrophilic dermatosis; Sweet’s syndrome; necrotizing Sweet's syndrome; soft tissue infection, immunocompromised, transsexual/transgender, LGBT Sweet’s Syndrome in Neutropenic Leukemia Patients Introduction
Also called acute febrile neutrophilic dermatosis, Sweet's syndrome is characterized clinically by acute onset fever that includes demarcated erythematous nodules that are painful to patients (Otero, Barber, Yeh & Quraishi, 2017). In addition, the disorder is characterized pathologically as being a dense neutrophilic infiltrate of the tissues located beneath the epidermis (Otero et al., 2017). Although necrosis of muscle and/or adipose tissue that is entirely attributable to Sweet's syndrome is rare, Otero et al. (2017) also report that another condition “has been recently reported as a subtype of Sweet's syndrome known as necrotizing Sweet's syndrome” (p. 182).
Acute febrile neutrophilic dermatosis was first reported by Dr. Robert Douglas Sweet in 1964 (Sweet, 1964). This first report of Sweet’s syndrome was based on a case study of eight female patients ranging in age from 32 to 55 years that presented with symptoms that would subsequently become the classical criteria for diagnoses of Sweet’s syndrome, including tender erythematous cutaneous plaques, fever, a dense neutrophilic infiltrate in the upper dermis and neutrophilia (Kazmi & Pemmaraju, 2014). It is especially noteworthy that the responses to glucocorticoid therapy were prompt among all eight of these original patients (Kazmi & Pemmaraju, 2014).
Over the intervening half-century, a growing body of research has investigated Sweet’s syndrome, and the findings to date indicate that the condition is characterized clinically by the rapid onset of tender erythematous skin lesions, neutrophilia, and fever. In the upper dermis, Sweet’s syndrome is characterized by a diffuse infiltrate of neutrophils histologically (Corbeddu, Pilloni, Pinna & Rongioletti, 2018). To date, there have been several variants of Sweet’s syndrome identified. For instance, according to Ghoufi, Ortonne, Ingen-Housz-Oro (2106), “Sweet’s syndrome has three main presentations: classical Sweet’s syndrome (idiopathic or associated with various inflammatory disorders), malignancy-associated Sweet’s syndrome, and drug-induced Sweet’s syndrome (mainly described with granulocyte or granulocyte-macrophage growth factors)” (p. 1).
Although there is no global racial predilection for Sweet’s syndrome, the three main groups of the disorder do have some other demographic differences in prevalence. For instance, according to Corbeddu and his associates (2018), “Clinical classification provides three main groups with distinctive features and association: classical or idiopathic, malignancy-associated, and drug?induced. The classical type occurs mostly in women between 30 and 60 years of age, with a female?to male ratio of 4:1” (p. 1530). Classic Sweet’s syndrome, however, has been identified in newborns as young as three days old (Chan & Lee, 2019).
Although the precise pathogenesis of Sweet’s syndrome remains unclear, there is a growing consensus among researchers that the development of the disorder is most likely multifactorial and includes the deregulation of cytokines and genetic predisposition that cause hypersensitive reactions to various tumor antigens, viruses or bacteria. The diagnostic criteria for the first type of Sweet’s syndrome were developed initially in 1986 but were subsequently modified by von den Driesch in 1994 (Corbeddu et al., 2018).
At present, the diagnostic criteria for Sweet’s syndrome are focused on the physical manifestation of various common symptoms. Typically, the cutaneous lesions in cases of Sweet’s syndrome occur as variously sized nodules and erythematous plaques that usually affect the neck and head as well as the back, trunk and mucosal surfaces less often (Kazmi & Pemmaraju, 2014). On occasion, Sweet’s syndrome can also result in a severe systemic response that affects the musculoskeletal system as well as the liver and lungs which can cause multi-organ failure, shock, and even death (Kazmi & Pemmaraju, 2014). In the majority of cases, though, such manifestations of Sweet’s syndrome are reversible through the rapid application of glucocorticoid therapies such as prednisone (Kazmi & Pemmaraju, 2014).
It is important to note, however, that the most commonly manifested aspects of acute febrile neutrophilic dermatosis with necrosis of deep soft-tissues are capable of closely resembling a necrotizing soft tissue infection, thereby complicating accurate and timely diagnosis (Otero et al., 2017). As discussed further following the case study report described below, these types of diagnostic constraints and challenges are especially problematic in cases of acute febrile neutrophilic dermatosis due to the need for early diagnosis and intervention in order to achieve optimal clinical outcomes.
While the first-line treatment of necrotizing soft tissue infection is surgical debridement, the use of this intervention for acute febrile neutrophilic dermatosis with necrosis of deep soft-tissues is contraindicated because it could cause more harm than good (Otero et al., 2017). Therefore, the early identification of necrotizing Sweet's syndrome represents a critical aspect of treatment by avoiding unneeded and the use of surgical interventions that are a contraindication for the disorder (Otero et al., 2017). Fortunately, when identified early on, the conventional interventions that are used to treat acute febrile neutrophilic dermatosis generally result in rapid and significant improvements in skin lesion as well as dermatosis-related symptoms (Kim & Chun, 2017).
It is also important to note, though, that necrotizing fasciitis that is caused by a polymicrobial infection is a potentially fatal infection of soft tissues which requires immediate treatment using broad-spectrum antibiotics as well as surgical debridement and fasciotomy also mimics acute febrile neutrophilic dermatosis (Kim & Chun, 2017). According to Kim and Chun (2017), “Although Sweet’s syndrome and necrotizing fasciitis are different diseases, a new variant of necrotizing Sweet’s syndrome that mimics necrotizing fasciitis has been reported in immunocompromised patients” (p. 2198).
Some people that are typically immunocompromised include members of the lesbian, gay, bisexual and transgender (LGBT) community. The fundamental reasons for such immunodeficiencies are multifaceted, but generally include the following factors: LGBT youth are 2 to 3 times more likely to attempt suicide; LGBT youth are more likely to be homeless; Lesbians are less likely to get preventive services for cancer; Gay men are at higher risk of HIV and other sexually transmitted diseases, especially among communities of color; Lesbians and bisexual females are more likely to be overweight or obese; Transgender individuals have a high prevalence of HIV/STDs, victimization, mental health issues, and suicide and are less likely to have health insurance than heterosexual or LGB individuals; Elderly LGBT individuals face additional barriers to health because of isolation and a lack of social services and culturally competent providers; LGBT populations have the highest rates of tobacco, alcohol, and other drug use (Lesbian, gay, bisexual and transgender health, 2019, para. 3). Although each of these categories of alternative lifestyles has its corresponding factors that exacerbate health problems, transgender individuals in particular also appear to be at high risk of developing acute febrile neutrophilic dermatosis, but determining the prevalence of this disorder among this population is problematic for a number of reasons. In general, the term “transsexual” is typically used to refer to people that have gender identities that are different from their birth sex (Meerwijk & Sevelius, 2017). It is not possible to estimate the population of transgender individuals in the United States with any degree of accuracy, though, since official records such as the U.S. Census, do not provide any data concerning current gender identity (Meerwijk & Sevelius, 2017).
What is known for certain is that the number of transsexual individuals in the United States has been on the increase in recent years, due in part to growing public acceptance and recognition that gender exists along a continuum for all humans, and some individuals are preternaturally compelled to align their gender identity with a sex that is different from that assigned at their birth (Meerwijk & Sevelius, 2017). In addition, more recent population surveys have included data concerning gender identity, and the findings that have emerged from this research confirm that growth in the LGBT community which has also contributed to growing public acceptance. This cycle has, in turn, encouraged even greater numbers of individuals to publicly reveal their gender identities and it is reasonable to suggest that additional scholarship in this area will show that clinicians can expect to encounter increasing numbers of the LGBT community in the future.
Based on their analysis of the most recent population survey data, Meerwijk and Sevelius estimate that the current population of transsexual individuals in the United States is 390 adults per 100,000 or approximately one million adults nationwide. Although Meerwijk and Sevelius concede that this estimate could be more reflective of rates for younger adults because these population segments accounted for more than half of the respondents in their analyses, they also emphasize that nationwide surveys in the future will likely identify even greater percentages of members of the LGBT community. Some indications of recent growth trends in this community can be easily discerned from the data depicted in Figure 1 below.

Figure 1. Meta-Regression Showing the Proportion of Transgender Adults against Survey Year
Source: Meerwijk & Sevelius, 2017
Note:
BRFSS = Behavioral Risk Factor Surveillance System
NCHA = National College Health Assessment
NIS = National Inmate Survey

There has also been a 19% increase in the number of female-to-male transsexual procedures that have been performed in the United States from 2015 to 2016 (U.S. gender confirmation surgery, 2019). A survey by the American Society of Plastic Surgeons found that while female-to-male transsexual procedures are still relatively rare, they account for nearly half (46%) of transsexual surgeries in the United States today (U.S. gender confirmation surgery, 2019).
Taken together, it is clear that the numbers of transsexuals is projected to increase dramatically in the United States over the next several years, and it is equally apparent that members of the LGBT community are faced with some profound health care issues that are attributable, at least in part, to their lifestyles, including the individual of interest to this case study report who is described further below. Case Report The individual of interest to this case study report is a 24-year-old female-to-male transsexual male presenting with recurrent myonecrosis of his upper chest and neck that was subsequently diagnosed as necrotizing Sweet’s syndrome. The patient reported a previous medical history of Hashimoto's thyroiditis as well as testosterone-induced cystic acne who originally sought help from a community hospital presenting with a 2-day history of increased sub-mental pain and swelling (Otero et al., 2017).
Following his first hospital admission, the patient was placed on broad-spectrum antibiotic therapy comprised of clindamycin, vancomycin and piperacillin/tazobactam. Based on the admitting clinicians’ suspicion that the patient’s condition was a necrotizing soft-tissue infection, a consultation was obtained from the otolaryngology-head and neck surgery service and the patient subsequently received therapeutic incision and drainage procedures for the involved areas (Otero et al., 2017).
Initially, the patient exhibited consistent symptomatic improvements during his 9-day stay in the hospital after initiation of the above-described therapeutic interventions and he was subsequently discharged to his home and directed to complete an intravenous course of antibiotics consisting of piperacillin/tazobactam for 7 days and then oral amoxicillin/clavulanate for another 14 days; in addition, the patient received oral doxycycline for a period of 21 days (Otero et al., 2017).
Notwithstanding the aggressive antimicrobial course of treatment the patient initially received post-discharge, he was readmitted on the 9th day following his discharge due to suspected recurrent necrotizing soft tissue infection. In addition, the patient also presented with rigors, fever, pronounced neck pain and a monomorphous pustular rash on his upper shoulders and back. A computed tomography image of the patient following his second hospital admission showed he had experienced fat stranding of the pectoralis major muscle as well as soft-tissue inflammation and gas in his sternocleidomastoid muscle, images that were congruent with a diagnosis of necrotizing soft tissue infection as shown in Figure 2 below.

Figure 2. Axial and Coronal CT imaging of the neck with IV contrast: (A) Axial and coronal views revealed small foci of air anterior to the right sternocleidomastoid muscle (A) and extensive
subcutaneous fat stranding from the right mandible interiorly to the mid thorax (B)
Source: Otero et al., 2017, p. 5

Extensive necrosis of the sternocleidomastoid fascia and surrounding tissue was identified upon surgical exploration, but there were no compelling causative organisms found on wound culture, acid-fast smear, Gram's stain, or mycobacterial culture derived from the patient’s blood cultures and tissue samples harvested during the exploratory surgical procedure. It should be noted, however, that highly rare Candida albicans were identified in a sample taken from the patient’s upper right chest. As a result, the patient’s medications were subsequently changed to meropenem, clindamycin, IV daptomycin, and fluconazole for broad-spectrum antimicrobial coverage based on a strong clinical suspicion of necrotizing soft tissue infection indicated by the computed tomography and empirical observations during the surgical procedure (Otero et al., 2017)
A dermatological consultation was obtained in order to rule out pyoderma gangrenosum due to the patient’s consistently negative body fluid and tissue cultures as well as his atypical rash. The pathology samples obtained from the patient’s debridement surgeries exhibited a number of outcomes that were congruent with a diagnosis of Sweet’s syndrome, including fat necrosis, with extensive neutrophilic inflammation and abscess formation as well as subcutaneous, skeletal muscle as shown in Figure 3 below.

Figure 3. Histologic images of the deep neutrophilic inflammation involving subcutaneous tissue (A) and extension into skeletal muscle (B).
Source: Otero et al., 2017, p. 8

The results of these clinical tests were provided to the hospital’s dermatopathology consultant service, but discussions with these providers as well as other members of the multidisciplinary treatment team suggested a higher possibility of an infectious etiology such as a nosocomial gram-negative infection for the patient’s symptoms compared to Sweet’s syndrome, particularly since the progression of muscle and skin necrosis had progressed so rapidly. Furthermore, it was not possible at this point to completely rule out an underlying infection as the cause of the patient’s symptoms given the broad-based antimicrobial regimen administered to the patient prior to his second hospitalization. Consequently, the patient was discharged and directed to complete the aforementioned 4-week IV course of meropenem, daptomycin and fluconazole together with supplemental visiting nurse assistants (Otero et al., 2017).
In spite of this new aggressive broad-spectrum IV antimicrobials regimen, the patient presented once again with pain, muscle necrosis of the neck and upper chest as well as recurrent erythema and he was subsequently readmitted. During the patient’s third inpatient stay, surgical debridement of the necrotic tissue was performed and the results were once again analyzed in an effort to identify any causative pathogens. The patient’s tissue cultures and gram’s stain were again negative, however, which resulted in a reevaluation of a non-infectious source for the patient's presenting condition (Otero et al., 2017).
The reevaluation of the test results obtained thus far together with empirical observations of his condition showed extensive myonecrosis and neutrophilic infiltration as well as the patient’s symptoms that were highly resistant to aggressive antimicrobial treatments which resulted in a revised diagnosis of acute febrile neutrophilic dermatosis with necrosis of deep soft-tissues. This revision is not uncommon when confronted with patients that present with these types of symptoms. For instance, according to Geller, Stone, Merola, et al. (2015), “When caring for an immunocompromised patient, the clinician must continually reevaluate the differential diagnosis if the patient has not had the expected response to therapy, bearing in mind that multiple, concurrent disease processes may be present” (p. 77).
Based on this revised diagnosis, the patient’s mediation regimen was subsequently changed to IV corticosteroid (i.e., 2mg/kg methylprednisolone) which resulted in decreased erythema and pain levels in the affected areas shortly after the administration of the first treatment. Based on this notable progress, the patient was once again discharged to home with a 2-week oral prednisone taper as well as a visiting nurse to provide assistance with caring for his wounds (Otero et al., 2017). Despite the revised diagnosis and treatment regimen, the patient experienced another bout with pain in his upper chest, right should and neck as well as severe erythema 14 days post-discharge while receiving 50 mg of prednisone which resulted in yet another inpatient stay (Otero et al., 2017).
Supplemental incision and drainage procedures, as well as IV corticosteroid therapy (2mg/kg methylprednisolone), were started during the fourth admission and because Sweet's syndrome continued to represent the primary diagnosis of his condition, the treatment strategy that was advised by the dermatological consultants was to minimize that trauma that is associated with surgical debridements due to the risk of skin lesions that are resistant to healing that are well documented with cases of necrotizing acute febrile neutrophilic dermatosis (Otero et al., 2017).
Based on the documented relationship between solid-organ tumors/hematologic cancers and acute febrile neutrophilic dermatosis, the patient had soft tissue excisional biopsies of the right neck and he was provided with a position emission tomography scan. In addition, the patient was also administered a diagnostic serum protein electrophoresis in order to rule out the possibility of malignancy as the source of his symptoms. The results of all of these tests were unremarkable and the patient was subsequently discharged to his home 3 weeks following his fourth admission with a prescribed pharmacological regimen of colchicine (1.5mg per day) and cyclosporine (3mg/kg per day) on a 6-week prednisone taper. The rationale for this regimen was explained by Otero and his associates thusly: “Although systemic corticosteroids are the gold standard therapy for Sweet's syndrome, colchicine and cyclosporine were used as adjuvant therapy, to decrease pathergy of the surgical sites” (2017, p. 183).
These multiple hospital admissions and challenges in formulating an accurate diagnosis of acute febrile neutrophilic dermatosis are not necessarily unusual, but they do underscore the constraints that are faced by clinicians who are confronted with a disorder that mimics numerous other conditions and is problematic to identify through conventional assessment protocols. Moreover, because acute febrile neutrophilic dermatosis is comparatively rare, clinicians may not consider this disorder early on which can result in unnecessary and potentially harmful surgical interventions. In this regard, Otero and his colleagues (2017) emphasize that “When soft tissue infections do not respond to debridement and broad-spectrum antimicrobial coverage, perioperative care providers should consider necrotizing Sweet's syndrome as an underlying cause” (p. 184).
Given the essentially experimental approach that this patient’s health care providers used to treat his symptoms based on erroneous diagnoses, it is clear that considering acute febrile neutrophilic dermatosis is a potential cause can speed the initiation of appropriate interventions. As Otero et al. (2017) conclude, “By facilitating the early diagnosis and appropriate management of unique conditions such as necrotizing Sweet's syndrome anesthesiologists can not only play a more visible role as leaders in the emerging perioperative surgical home model but also may prevent significant patient morbidity and reduce unnecessary utilization of healthcare resources” (p. 185). In sum, it has been more than a half-century since Sweet’s syndrome was first identified, but it is reasonable to suggest that far too many clinicians lack the knowledge and understanding of this disorder to identify it accurately early on, but there are some steps that can be taken to help treat this condition once it has been diagnosed, and these issues are discussed further below. Discussion The background and case study report presented above make it clear that the number of immunocompromised individuals is on the rise (Kim & Chun, 2017) and that it is reasonable to posit that clinicians will encounter increasing numbers of patients that present with symptoms mimicking Sweet’s syndrome. The research was consistent in emphasizing the need for early diagnosis of Sweet’s syndrome to achieve optimal clinical outcomes, but it was also shown that the symptoms of this disorder resemble those of several other conditions, thereby complicating accurate and timely diagnosis.
In addition, the research also showed that the dermatologic condition, Sweet's syndrome, has been associated with a number of different disease states, supported by a growing body of scholarship including hundreds of case series and case reports (Otero et al., 2017). Likewise, Sweet’s syndrome and its associated symptoms have also been examined systematically in a review by Cohen and Kurzock (2003). The findings that emerged from this research have been supplemented with additional studies concerning the different classifications for Sweet’s syndrome.
The major classifications of Sweet's syndrome were shown to be as follows:
1. Idiopathic (classic) subtype. This subtype of Sweet's syndrome is more common in women and typically manifests prior to an upper respiratory tract infection. This subtype is associated with underlying inflammatory bowel disease, autoimmune disorders, recent vaccination, and pregnancy. An example of a classic case of Sweet’s syndrome is depicted in Figure 4 below.

Figure 4. (a, b, and c). Tender, red Sweet's syndrome lesions in a woman with the classical form of the dermatosis. There is an erythematous plaque, 5 cm in diameter, with a pseudovesicular appearance on the left shoulder of the patient (a). A nodular lesion, 1 cm in diameter, is present on the lateral left arm (b). Painful, erythematous, pseudovesicular plaques of acute febrile neutrophilic dermatosis are present on the left hand (c).
Source: https://upload.wikimedia.org/wikipedia/commons/thumb/d/d8/Sweet-syndrome_skin.png/1024px-Sweet-syndrome_skin.png
2. Malignancy subtype. The malignancy subtype is found in approximately 20 percent of patients with Sweet's syndrome, where symptomatology has been reported during cancer resurgence or prior to oncologic diagnosis. The most common cancer associated with Sweet's syndrome is acute myelogenous leukemia; however, solid tumors of the genitourinary tract, breast, and gastrointestinal tract have been reported with acute febrile neutrophilic dermatosis as well. The malignancy subtype of Sweet’s syndrome is depicted in Figure 5 below.

Figure 5. (A) Multiple red-violet, well-demarcated, indurated, and edematous papules and plaques on the left arm and back (B). (C) Closer inspection of the papule revealed focal areas of pseudovesiculation and focal areas of pseudovesiculation and focal ulceration.
Source: Clark, Sarcon & Sivamani, 2017
3. Drug-induced subtype. The final subtype of Sweet’s syndrome has been reported following the initiation of a number of different medications, with the most common being colony-stimulating factors with antibiotics such as trimethoprim-sulfamethoxazole) or granulocyte-colony stimulating factors (Otero et al., 2017). A subtype of acute febrile neutrophilic dermatosis with evidence of fat and muscle necrosis as evinced in the patient presented in the case study by Otero et al. (2017) but this subtype of the disorder was also identified in a three-patient case series by Kroshinsky, Alloo, Rothschild et al. (2017) only recently.
Some of the known risk factors for Sweet's syndrome for these three patients included hematologic malignancy and the administration of granulocyte colony-stimulating factor. Despite these known risk factors for Sweet's syndrome, two of the three patients in the Kroshinsky et al. (2017) series were treated initially for a necrotizing soft tissue infection using surgical debridement; in addition, all three patients were administered IV antibiotics in spite of repeat negative Gram's staining and tissue cultures. The other patient in the Kroshinsky et al. (2017) series was not surgically debrided due to an early diagnosis of necrotizing Sweet's syndrome by the dermatology/dermatopathology service (Kroshinsky et al., 2012).
Some of the defining characteristics that distinguish classical Sweet’s syndrome from the drug-induced subtype that can help clinicians diagnose the condition early on include those set forth in Table 1 below.
Table 1.
Diagnostic criteria for classical Sweet's syndrome versus drug-induced Sweet's syndrome
Classical
Drug-induced

(1) Abrupt onset of painful erythematous plaques or nodules
(A) Abrupt onset of painful erythematous plaques or nodules

(2) Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis
(B) Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis

(3) Pyrexia >38°C
(C) Pyrexia >38°C

(4) Association with an underlying hematologic or visceral malignancy, inflammatory disease, or pregnancy, OR preceded by an upper respiratory or gastrointestinal infection or vaccination
(D) Temporal relationship between drug ingestion and clinical presentation, OR temporally-related recurrence after oral challenge

(5) Excellent response to treatment with systemic corticosteroids or potassium iodide
(E) Temporally-related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids

(6) Abnormal laboratory values at presentation (three of four): erythrocyte sedimentation rate >20 mm/hr; positive C-reactive protein; >8,000 leukocytes; >70% neutrophils

Source: Cohen, 2007

The key objective in treating patients with Sweet’s syndrome is to limit the level of surgical interventions that are used based on its known relationship with skin lesions and other dermatological conditions that are difficult to treat and slow to heal termed pathergy (Otero et al., 2017) According to Otero and his associates (2017), “Pathergy is a non-specific inflammatory response to intradermal trauma, characterized by deep perivascular mixed inflammatory cell infiltrate with neutrophils on histopathology” (p. 184). In fact, even comparatively minor trauma can cause pathergy so it is imperative to avoid any type of unnecessary surgical intervention to prevent any additional inflammatory damage (Otero et al., 2017).
Similar to the patient in the Otero et al. (2017) case study report, all of the patients in the case series by Kroshinsky et al. (2012) also experienced negative culture samples and suffered sustained clinically deterioration during their course of antimicrobials only. Moreover, all of these patients demonstrated clinical improvements following the initiation of systemic corticosteroids (Otero et al., 2017). Indeed, the administration of systemic corticosteroids is consistently cited as the treatment of choice for this disorder. It should be noted, though, that the patient in the Otero et al. (2017) case study report did not suffer from an underlying malignancy such as those experienced by the patients in the Kroshinsky et al. (2012) series, but the Otero et al. (2017) patient did exhibit some clinically relevant features such as Hashimoto's thyroiditis that have been independently associated with inducing acute febrile neutrophilic dermatosis (Otero et al., 2017).
Notwithstanding this independently established association between Hashimoto’s thyroiditis and Sweet’s syndrome, there has not been a causative link between these two disorders established to date. Nevertheless, because both of these disorders presented in the Otero et al. (2017) patient, these authorities posit that they were both caused by a hypersensitivity reaction to an unidentified antigen wherein the potential antigenic trigger is multifactorial and may include viral, tumor antigen or bacterial sources.
Furthermore, the Otero et al. (2017) patient’s cystic acne that was induced by testosterone was being treated with minocycline, another drug that has been associated with the onset of drug-induced Sweet's syndrome. In addition, this type of acne is a known side effect of treatments using testosterone (Wierckx, Van de Peer F, Verhaeghe, et al. 2014). Due to the significant prevalence level of severe acne following therapy using testosterone, Otero et al. (2017) caution that it is vitally important for clinicians to continuously monitor patients that are receiving androgen treatments, most especially in patients with gender identity disorders that may be immunocompromised and have other unique needs that must be taken into account when formulating an appropriate intervention.
An especially noteworthy observation by Otero et al. (2017) concerns the lack of research in this area. In this regard, Otero et al. (2017) emphasize that “Furthermore, despite increased recognition of gender identity disorder over the past decade, there remains a paucity of literature that investigates the serious dermatologic issues related to androgen therapy in transsexual males” (p. 185). Therefore, ongoing vigilance is absolutely required in order to identify necrotizing Sweet’s syndrome early on so as to avoid any unnecessary surgical procedures that are commonly used with conditions that mimic its symptoms which may trigger the inflammatory process (Otero et al., 2017). In addition, Otero et al. (2017) advise, “Care providers should be aware of the major associations and clinical hallmarks exhibited by Sweet's syndrome, such as painful erythematous skin lesions, fever, and diffuse neutrophilic infiltrate of the dermis on histology” (p. 185). Some of the key features that should alert clinicians to consider Sweet’s syndrome as a diagnosis include the following: Acute onset of painful, red papules or nodules; Fever >38 degrees C Associated diseases: Haematological or visceral malignancy, inflammatory bowels disease, pregnancy; or preceded by upper respiratory tract/gastrointestinal infection; Arthralgia, myalgia, malaise & ocular involvement; and High inflammatory markers: WCC >8x109 with neutrophils >70%, ESR >20 mm/h; high CRP (Chan & Lee, 2019, p. 23). While necrotizing acute febrile neutrophilic dermatosis remains rare, this disorder should be included when presented with patients exhibiting the symptoms of necrotizing soft tissue infections based on their similar symptoms and imaging results. This level of hypervigilant care must be performed by a multidisciplinary treatment team. In this regard, Otero et al. (2017) add that “Diagnosis of necrotizing Sweet's syndrome typically requires close communication between perioperative physicians (i.e. anesthesiologists, intensivists, and surgeons), as well as consultation by dermatology and/or dermatopathology” (p. 185).
Finally, the ability to identify and rapidly coordinate appropriate interventions for necrotizing Sweet’s syndrome during preoperative consultation with anesthesiologists may facilitate subsequent follow-up inpatient and outpatient care using the emerging perioperative surgical home (PSH) model (Otero et al., 2017). According to the guidance provided by the American Society of Anesthesiologists (2019), “In the PSH model, the patient’s experience of care is coordinated by a director of perioperative services, additional surgical home leadership, and support personnel which constitute an interdisciplinary team. The expected metrics include improved operational efficiencies, decreased resource utilization, a reduction in length of stay and readmission, and a decrease in complications and mortality-resulting in better patient experience of care” (Perioperative surgical home overview, para. 2). The PSH model is depicted in Figure 6 below.

Figure 6. Perioperative surgical home model overview
Source: https://sites.asahq.org/~/media/sites/psh/images/psh_overviewchart600px.png
Given the challenges that are associated with the early diagnosis and ongoing treatment of necrotizing Sweet’s syndrome, this level of multidisciplinary care is absolutely essential in order to prevent unnecessary surgical procedures and treatment protocols that are designed to treat the disorders that closely mimic this disorder’s signs and symptoms. Conclusions The research showed that while there is not a racial predisposition for Sweet’s syndrome, there are some demographic differences involved in its prevalence level. The classical diagnostic criteria for this disorder were shown to include fever, tender erythematous cutaneous plaques, a dense neutrophilic infiltrate in the upper dermis and neutrophilia. The research also showed that the research to date has identified three main groups of Sweet’s syndrome, each with its own distinctive features: classical or idiopathic, malignancy-associated, and drug?induced. The classical type of Sweet’s syndrome is most commonly found in women aged 30 to 60 years, with females being four times as likely to develop the disorder as males. Although necrotizing acute febrile neutrophilic dermatosis is still regarded as a rare disorder, the research was also consistent in showing that the numbers of immunocompromised individuals in the United States has increased dramatically in recent years and current projections indicate that this growth rate will continue well into the foreseeable future. Therefore, clinicians should consider Sweet’s syndrome as a potential differential diagnosis when presented with patients exhibiting the symptoms of necrotizing soft tissue infections due to the similarity of symptoms and imaging results as well as the need for early diagnosis and appropriate treatments in order to optimize clinical outcomes. In the final analysis, it is reasonable to conclude that while the prevalence of Sweet’s syndrome remains unclear, clinicians can expect to encounter increasing numbers of these cases in the future as the number of immunocompromised individuals in the United States also continues to grow.