Dermatologic Emergencies CME Part II: Infections and infection-related complications

Mohammed Shanshal

Department of Dermatology, Basildon University Hospital NHS Foundation Trust, UK

Corresponding author: Mohammed Shanshal, MD, E-mail:

How to cite this article: Shanshal M. Dermatologic Emergencies CME Part II: Infections and infection-related complications. Our Dermatol Online. 2022;13(4):483-494.
Submission: 18.06.2022; Acceptance: 01.10.2022
DOI: 10.7241/ourd.20224cme.2

Citation tools: 

Related Content

Copyright information
© Our Dermatology Online 2022. No commercial re-use. See rights and permissions. Published by Our Dermatology Online.


This section covers the strategies for managing the dermatologic infectious diseases and how they present in emergency and acute settings. In order to keep the staff and patients safe, emergency physicians should be able to limit the nosocomial infection spread.

Key words: Necrotizing fasciitis; Purpura fulminans; Meningococcemia; Toxin-mediated Staphylococcal diseases; Leprosy reactions


Necrotizing fasciitis (NF) is classified into four types according to the causative microorganism (Table 1). Trauma is the most identifiable etiology and includes external injuries and surgeries. However, cryptogenic (spontaneous) infections may occur deep within tissues without a portal of entry. Risk factors include immunosuppression, especially diabetes, malignancy, obesity, and alcoholism [1].

Table 1: Types of necrotizing fasciitis [12].

The early cutaneous changes of NF can mimic cellulitis (severe tenderness, erythema, warmth, and swelling that does not respond to antibiotics), progressing into severe pain out of proportion to clinical findings that may be followed by anesthesia as cutaneous nerves are destroyed. The erythema evolves to a dusky grayish color with rapidly spreading woody edema and malodorous watery discharge [2]. If not diagnosed early, systemic manifestations of shock or organ dysfunction may follow [3].

Fournier gangrene is an NF subtype localized to the genitalia, perineum, anus, and, occasionally, the skin of the lower abdomen that commonly occurs in adults with significant underlying comorbidities, especially diabetes [4,5].

Physicians should be aware of the potential pitfalls that may delay the early diagnosis of NF (Table 2).

Table 2: Pitfalls in the diagnosis of NF [13].

Diagnosis is usually based on a combination of local and systemic clinical findings, radiological imaging, histology, and Gram staining with a microbial culture of tissue biopsies [6].


Any delay in the diagnosis could prove to be fatal; early and extensive surgical debridement (fasciotomy) is the mainstay treatment (Fig. 1) in addition to broad-spectrum antibiotics (including gram-positive, gram-negative, and anaerobic coverage) and hemodynamic support. Survival significantly increases with early surgical intervention, preferably within 24 hours of hospital admission [7-9]. The role of hyperbaric oxygen and intravenous immunoglobulin (IVIg) is controversial [10,11].

Figure 1: Necrotizing fasciitis. Flowchart of the suggested clinical, laboratory and radiological findings of NF. Fasciotomy is the mainstay treatment of necrotizing fasciitis. ^Laboratory investigations should not delay the urgent surgical debridement. *delayed surgical debridement (> 12 hours) associated with poor outcome.


Meningococcemia is a rare, severe form of infection caused by Neisseria meningitidis, an aerobic gram-negative diplococcus. Complement deficiency and drugs that inhibit the complement pathway, such as eculizumab, are well-known risk factors for meningococcemia [14,15]. Early manifestations are often nonspecific, such as fever, headache, malaise, and nausea/vomiting. Although the characteristic petechial rash is a more specific finding, it is only observed in 45% to 65% of cases [16,17]. The petechial or purpuric eruption with an irregular outline and central gunmetal gray color may progress to purpura fulminans with severe DIC. Subsequently, the patient may show signs of sepsis and septic shock, with the rapid onset of hypotension, pericarditis, cardiac tamponade, acute adrenal insufficiency due to hemorrhage (Waterhouse-Frederickson syndrome), and multi-organ failure [18,19]. Meningococcal septicemia occurs in 20% of cases and is associated with poor outcomes. Meningiococcimeia is a clinical diagnosis that can be confirmed with blood culture; however, investigations should not delay treatment initiation [20,21].

Practical pearls:

  • Non-responsive skin infection with disproportionate pain, pain that extends beyond the apparent infection margins, and/or hypoesthesia or anesthesia should raise the suspicion of necrotizing fasciitis.
  • Surgical therapy should be sought once the diagnosis of NF is clinically suspected and should not be delayed by diagnostic imaging. Delayed diagnosis is associated with increased risk of morbidity and mortality.


    Antibiotics can dramatically improve patient outcomes. Third-generation cephalosporin, cefotaxime 2g qds or ceftriaxone 2 g bd IV is recommended as soon as meningococcemia is suspected. Patients with a history of anaphylaxis to cephalosporins should consider chloramphenicol and quinolones as alternatives. Antibiotics should be administered alongside fluid resuscitation and supportive measures for sepsis, as indicated [22,23] (Fig. 2). For close contacts, rifampicin and ciprofloxacin can be used as chemoprophylaxis [24].

    Figure 2: Meningococcemia. Key points in the management of meningococcemia include antibiotics, supportive measures and chemoprophylaxis for close contacts.

    Practical pearls

    • Meningiococcimeia should be suspected in any patient with febrile illness and petechial rash.
    • No investigation should delay antibiotic administration.
    • If intravenous access cannot be obtained within 15 minutes, intramuscular or intraosseous ceftriaxone/cefotaxime or penicillin should be used.


    Staphylococcal scalded skin syndrome (SSSS) is a potentially life-threatening disorder. It is caused by hematogenous dissemination of the exfoliative toxins (ETA and ETB) of phage group II strains (e.g. types 55 and 71) of S. aureus [25,26] (Fig. 3). It occurs primarily in infants and adults with chronic renal insufficiency or immunodeficiency [27,28].

    Figure 3: Staphylococcal scaldeWd skin syndrome and toxic shock syndrome. Spectrum of toxin-mediated Staphylococcal diseases.

    Prodromal symptoms often include fever, irritability, and poor oral intake with skin tenderness, which can be so severe that the infant will refuse to lie down or allow anyone to hold them. Erythema typically starts on the face and intertriginous sites with characteristic periorificial crusting and radial fissuring. Within 1 to 2 days, the rash progresses into superficial blistering and desquamation with a positive Nikolsky sign [29]. Complications of SSSS include sepsis, pneumonia, dehydration, electrolyte imbalance, and hypothermia [30].

    Diagnosis is mainly based on the clinical findings. This can be confirmed by culturing S. aureus from any suspected primary focus of infection, such as the nasopharynx, conjunctiva, umbilicus, and diaper area [31,32]. Skin biopsies usually show intra-epidermal cleavage at the level of the granular layer [33].


    Patients with SSSS are preferably treated in burn or intensive care units. Immediate empiric treatment with intravenous anti-staphylococcal antibiotics such as nafcillin, oxacillin, or flucloxacillin is recommended in most patients for a minimum of 1 week [34,35]. If MRSA is suspected, antibiotics with MRSA coverage (e.g., vancomycin or linezolid) are indicated [36]. Clindamycin can be used as an adjunct therapy to inhibit the production of exotoxins [37]. Supportive care is a critical component of management, including skin and wound care and the management of potential fluid and electrolyte abnormalities [38,39].

    Practical pearls

    • Unlike pediatric patients, adults with SSSS usually have underlying morbidities like chronic renal disease or immunosuppression. Hence every adult patient with SSSS should be screened for an underlying predisposing risk factor.
    • SSSS can be differentiated from other similar blistering disorders by the lack of mucosal involvement and more superficial epidermal involvement on histological examination.


      Toxic shock syndrome is an acute life-threatening illness caused by Staphylococcus aureus or group A Strep superantigen exotoxins (Fig. 4). TSS toxin 1 (TSST-1) is responsible for most menstrual TSS cases and about half of the non-menstrual TSS, where staphylococcal enterotoxins are also implicated [40]. Non-menstrual TSS can occur in the settings of soft tissues and respiratory infections, post-surgical and postpartum wound infections, burns, barrier contraceptive use, and retained foreign bodies such as nasal packing [41]. TSS is characterized by rapid onset of fever, hypotension, multi-organ system involvement, diffuse macular erythroderma and desquamation 1 to 2 weeks after the onset of illness, typically involving the palms and soles [42,43].

      Figure 4: Purpura fulminans. Flowchart of approach to the patient presented with PF [61].

      In contrast to staphylococcal TSS, streptococcal TSS is more likely to cause respiratory symptoms, is less likely to cause a typical cutaneous reaction and is associated with a poorer prognosis. Mortality associated with streptococcal TSS is 5%-10% in children compared to 30%-80% in adults [44].

      The diagnosis of staphylococcal TSS can be established based on the CDC clinical and laboratory criteria (Table 3).

      Table 3: CDC case definition for staphylococcal TSS [51].


      Early recognition and institution of therapy are essential to avoid a fulminant course. Hemodynamic stabilization with intravenous fluids and/or vasopressor agents is the most crucial aspect of treatment. Parental beta-lactamase-resistant antistaphylococcal antibiotics are needed to eradicate bacteria and prevent recurrence [45]. Adjunctive therapeutic measures include clindamycin [46,47] to suppress toxin production, intravenous immunoglobulin (IVIG) to neutralize the toxin- [48,49], and surgical removal of the foreign bodies.

      Practical pearls

      • A high index of suspicion is required while making the diagnosis of TSS; CDC based definition criteria are mainly for research purposes, some of the criteria can only be established in a retrospective manner, and most importantly, not all the cases of TSS meet the CDC criteria.
      • The presentation of non-menstrual TSS is identical to the menstrual one, but it can occur in both sex in more comprehensive clinical settings, and it is associated with a higher mortality rate.
      • The seven Rs can be used to guide the management of TSS [50]
        • Recognition
        • Resuscitation
        • Removal of infection source
        • Rational choice of antibiotics
        • Role of adjuvant therapy
        • Review progression
        • Reduction of secondary infection in close contacts


      Purpura fulminans (PF) is a rapidly progressive, highly thrombotic disorder that mainly affects neonates and children that accompany bacterial, and more rarely, viral infections. PF is characterized by a high mortality rate caused by disseminated thrombosis and subsequent multi-organ failure [52]. The clinical picture of PF is often dominated by shock with hypotension and hypovolemia. The cutaneous lesions are marked by vascular occlusion features, including retiform, branching purpuric patches that rapidly evolve into hemorrhagic necrosis, and are sometimes preceded by bulla formation [53,54]. In the acute phase, the laboratory findings of PF are those of the associated DIC, including thrombocytopenia, hypofibrinogenemia, increased fibrin degradation products (FDP), and prolonged prothrombin (PT) and activated partial thromboplastin (aPTT) times. Measurements of protein C (PC) and S (PS) are additional essential investigations that should be performed at presentation [55]. The most important underlying triggers and patho-mechanisms of PF are presented in Table 4.

      Table 4: Underlying causes and pathogenesis of PF.


      PF of any cause requires urgent intervention to avoid a rapidly progressive multi-organ thrombotic injury. Most patients require complete supportive care and urgent broad-spectrum antimicrobial therapies (for sepsis). PF with DIC also requires urgent FFP (10-20 ml/kg every 8-12 h) to replace the consumed pro-coagulant and anticoagulant plasma proteins. Additional platelet concentrates (10-15 ml/kg) and cryoprecipitate (5 ml/kg) may be necessary for significant thrombocytopenia and hyperfibrinogenemia, respectively [56]. PC concentrates are licensed for cases with severe heritable PC deficiencies [57,58]. Anticoagulants can be used cautiously for PF complicated by large-vessel venous thrombosis or central venous catheter thrombosis [59,60].

      Practical pearls

      • Mortality in PF is mainly caused by overwhelming thrombosis, and survivors may suffer from significant scarring and limbs amputation
      • After few weeks of clearing the infection, death may occur due to thrombi obstructing small/medium blood vessels. Hence physicians should be vigilant to thrombotic complications while treating the underlying septic trigger.
      • Due to overlapping causes and lack of pathognomonic characteristics, the diagnose of purpura fulminans may be challenging.
      • If the diagnosis of purpura fulminans is suspected, it should be assumed to be related to acute infection until proven otherwise.


      Ecthyma gangrenosum is an uncommon, fulminant cutaneous infection classically associated with Pseudomonas aeruginosa bacteremia; however, other causative pathogens can produce clinically indistinguishable lesions [62-64]. The cutaneous manifestations of EG result from occlusion of the subcutaneous blood vessels by proliferating organisms in the media and adventitia layers. Infection typically occurs in critically ill or immunocompromised patients with severe neutropenia, representing a major predisposing factor [65]. Several case reports have described EG in previously healthy immunocompetent individuals without underlying identifiable causes [66].

      Cutaneous lesions of EG initially appear as painless, erythematous macules that rapidly evolve into hemorrhagic pustules and/or bullae with an erythematous border. Ultimately the lesions progress to necrotic ulcers with surrounding erythema and a central black Eschar. While EG can occur at any anatomical location, the anogenital area and extremities are most commonly involved, followed by the trunk and face [67,68].

      Urgent diagnosis should be made based on the clinical characteristics of the lesion, supported by blood and wound bacteriologic cultures and tissue biopsy. Biopsy of the EG lesion typically shows perivascular hemorrhage and infiltration of neutrophilic granulocytes with central necrosis. The diagnosis of EG should alert the physician to the possibility of an underlying Pseudomonas bacteremia [69]. The unfavorable prognosis in EG is linked to several factors presented in Table 5.

      Table 5: Factors associated with higher EG mortality.


      Although the usual outcome of EG is poor, rapid and aggressive appropriate systemic treatment can lead to a better prognosis. Empiric antimicrobial therapy typically includes antipseudomonal beta-lactams, aminoglycosides, and/or fluoroquinolones alone or in combination. Once the causative organism and its antibiotic sensitivity are known, directed therapy can be tailored to these results. Surgical excision and debridement under antibiotic cover are indicated for progressive lesions [70,71].

      Practical pearls

      • Undermined ulcerative skin lesion in an immunosuppressed patient should raise the suspicion of ecthyma gangrenosum.
      • The presence of these lesions should increase the possibility of bacteremia/sepsis, especially with P. aeruginosa, and should encourage blood culture collection.
      • Early initiation of appropriate antibiotic therapy is imperative as it can change the prognosis.


      Anthrax is primarily a zoonotic disease. The main route of transmission is contact with, or inhalation of Bacillus anthracis, a gram-positive bacillus. Most cases are due to occupational exposure to infected animals or their products[72,73]. Anthrax remains a global concern because it can potentially be used as a biological weapon [74-76].

      The disease occurs primarily in three forms: cutaneous, respiratory, and gastrointestinal, with cutaneous anthrax accounting for 95% of the cases globally.

      With proper treatment, cutaneous anthrax can be self-limiting without complications in 80%-90% of cases. Rarely, extensive edema, septic shock, and meningitis can result from the lymphohematogenous spread of infection [77].

      Bacillus anthracis is usually introduced at the site of a cut or abrasion, on exposed areas such as the arms, face, or neck. Mild cutaneous anthrax usually starts as a painless purpuric macule or papule resembling an insect or spider bite evolving into a vesicle filled with clear or serosanguineous fluid. The vesicle usually ruptures and ulcerates, leaving a painless black necrotic eschar. The eschar is often surrounded by striking, non-pitting edema and may be accompanied by lymphadenopathy. Over the next 1-2 weeks, eschar dries and sloughs with no permanent scarring [78,79]. Severe cutaneous anthrax is defined by the presence of a large cutaneous lesion with a bullous reaction, extensive edema and systemic symptoms, including fever, tachycardia, and tachypnea. Without antibiotic treatment, mortality may be as high as 20%, usually due to septicemia [80,81].


      If the cutaneous anthrax is associated with a concomitant inhalational exposure, the CDC recommended antibiotics for at least 60 days, compared to a 7-10-day course for a purely cutaneous exposure, quinolones and doxycycline are first-line agents [82].

      Practical pearls

      • „Malignant pustule” is an abandoned misnomer of cutaneous anthrax as pustules are rarely present, and their presence decreases the likelihood of anthrax diagnosis.


        Eczema herpeticum is a life-threatening viral infection that presents as a background to other dermatological conditions. It is mainly caused by herpes simplex virus type1 (HSV1), although HSV2, Coxsackie A16, smallpox, and vaccinia have all been implicated [83,84]. The majority of EH cases occur in infants/children more than adults with pre-existing atopic dermatitis; however, it can occur in other conditions with impaired skin barrier such as Darier disease, Hailey-Hailey disease, various bullous diseases, burns, ICD, mycosis fungoides, Sézary syndrome, and ichthyoses [85].

        Eczema herpeticum is characterized by clusters of umbilicated, dome-shaped vesicles that quickly progress to monomorphic, punched-out erosions with hemorrhagic crusts. The patient may generally feel unwell, commonly with fever and lymphadenopathy. Rarely EH may result in the hematogenous spread of HSV with hepatic, pulmonary, ocular, and CNS manifestations [86-89]. If not treated promptly, the mortality rate of EH can be 6%-10%, primarily due to bacterial superinfection. EH is a clinical diagnosis and can be confirmed by scraping the blister for viral culture, direct fluorescent antibody staining, PCR sequencing, or Tankz smear [90].


        Early diagnosis and antiviral treatment can prove lifesaving. Systemic antiviral chemotherapy such as a 7-day course of intravenous acyclovir (5-10 mg/kg per dose administered intravenously) three times daily which may be prolonged according to the clinical course of the disease [91,92].

        Practical pearls

        • Eczema herpeticum can be easily misdiagnosed as an acute exacerbation of atopic dermatitis, signs that encourage the diagnosis of eczema herpeticum in children with atopic dermatitis include [93]:
          • Areas of rapidly worsening, painful eczema
          • Clustered blisters consistent with early-stage cold sores
          • Punched-out erosions (circular, depressed, ulcerated lesions) usually 1-3 mm that are uniform in appearance (these may coalesce to form larger areas of erosion with crusting)
          • Possible fever, lethargy, or distress.


        Leprosy reactions are a significant cause of hospitalization and disability. They occur primarily in patients with lepromatous and borderline leprosy due to immune-mediated inflammation involving the skin, nerves, eyes, and other body organs (Fig. 5). These reactions may occur before diagnosis, during treatment, or after treatment completion [94,95]. Leprosy-related conditions requiring urgent referral for assessment and treatment are summarized in Table 6.

        Figure 5: Leprosy reactions. Leprosy reactions include type 1 reaction (reversal or upgrading reaction), type 2 reaction (erythema nodosum leprosum) and type 3 reaction (Lucio phenomenon, erythema necroticans).
        Table 6: Indications of urgent referral for assessment and treatment in leprosy [96].

        Type 1 reaction (reversal or upgrading reaction)

        Type 1 reaction (T1R) is a Th1 mediated delayed-type hypersensitivity reaction to M. leprae antigens. T1R occurs primarily in patients with borderline leprosy (BT, BB, BL) with immunological recovery during or after treatment, which causes a sudden increase in cell-mediated immunity and a shift toward the polar tuberculoid end of the Ridley-Jopling leprosy spectrum [97,98]. It is characterized by increased inflammation of established skin lesions, and the emergence of new skin lesions with acute neuritis. Neuritis causes loss of sensory and muscle function, which is generally associated with nerve pain, but in some cases without pain or nerve tenderness (silent neuritis) [99]. In clinical practice, type 1 reactions can’t be diagnosed using laboratory tests and the diagnosis is usually made based on clinical manifestations [100].

        Type 2 reaction (erythema nodosum leprosum)

        Erythema nodosum leprosum (ENL) is a systemic inflammatory condition caused by cutaneous and systemic small-vessel vasculitis. It is characterized by Th2 mediated excessive immune complex formation and deposition that occurs primarily in patients with LL and BL [101,102]. ENL is characterized by the sudden onset of nodular skin lesions associated with features of systemic vasculitis including, iridocyclitis, lymphadenitis, hepatosplenomegaly, orchitis, glomerulonephritis, joint swelling, and dactylitis (Table 7). The main risk factor for ENL is lepromatous leprosy with skin infiltration, high bacterial load, and an age of less than 40 years [103]. The diagnosis of ENL is primarily based on clinical findings. Skin biopsy may be helpful when the diagnosis is unclear [104].

        Table 7: WHO criteria of severe ENL [105].

        Lucio phenomenon (erythema necroticans)

        The lucio phenomenon is an uncommon immunological reaction that occurs in patients with diffuse non-nodular lepromatous leprosy, mainly in western Mexico [106]. It is characterized by irregular purpuric macules, especially below the knees that evolve into bullous lesions that rapidly ulcerate. This severe reaction primarily occurs in patients who have not received treatment, and it may coincide with ENL [107,108].


        Lepra reactions require urgent treatment as they can lead to irreversible deformities. Thus, early diagnosis and timely initiation of anti-inflammatory measures are crucial. Multidrug therapy (MDT) should be continued or initiated (in those who first present with T1R). Aspirin or paracetamol should be administered to reduce pain and fever, and rest is essential. Corticosteroids are the cornerstones of type 1 reactions and acute neuritis therapy. The dose may be adjusted according to neurological function assessment [109,110]. Alternative immunosuppressive agents, including azathioprine, cyclosporine, and methotrexate, may play a role in the management of severe T1R non-responsive to corticosteroids [111-113].

        ENL is often recurrent, chronic, and a significant health problem in countries where leprosy is endemic. Therefore, treatment is often prolonged and requires several months to years of therapy. Treatment for ENL aims to resolve skin lesions, relieve pain, and reduce and prevent complications by reducing systemic and neural inflammation. Limited high-quality clinical data are available to guide drug choice, dosing, and duration. However, corticosteroids, clofazimine, thalidomide, and pentoxifylline, either alone or in combination, are the most commonly used drugs to treat ENL [114,115]. Because of its well-known teratogenic side effects, the WHO does not support the use of thalidomide [105]. Patients with Lucio’s Phenomenon usually respond well to the initiation of MDT alone or in combination with corticosteroids [116].

        Practical pearls

        • Reversal reaction is one of the presentations of immune reconstitution inflammatory syndrome (IRIS) in HIV patients after commencing the HAART; hence patients with reversal reaction should be screened for HIV co-infection as a triggering factor.
        • In order to prevent or alleviate the nerve damage and its complications, long-term follow-up is critical for patients who developed leprosy reactions.
        • Unlike the erythema nodosum, ENL mainly affects the face and extensors of the upper and lower extremities.


        1. Green RJ, Dafoe DC, Rajfin TA. Necrotizing fasciitis. Chest. 1996;110:219-29.

        2. Frank J, Barker JH, Marzi I. Necrotizing fasciitis of the extremities. Eur J Trauma Emerg Surg. 2008;34:229-36.

        3. Leiblein M, Marzi I, Sander AL, Barker JH, Ebert F, Frank J. Necrotizing fasciitis:treatment concepts and clinical results. Eur J Trauma Emerg Surg. 2018;44:279-90.

        4. Morpurgo E, Galandiuk S. Fournier’s gangrene. Surg Clin North Am. 2002;82:1213-24.

        5. Levenson RB, Singh AK, Novelline RA. Fournier gangrene:role of imaging. Radiographics. 2008;28:519-28.

        6. Desta R, Yee J. Necrotizing fasciitis. JETem. 2020;5:S1-25.

        7. Misiakos EP, Bagias G, Patapis P, Sotiropoulos D, Kanavidis P, Machairas A. Current concepts in the management of necrotizing fasciitis. Front Surg. 2014;29;1:36.

        8. Goh T, Goh LG, Ang CH, Wong CH. Early diagnosis of necrotizing fasciitis. Br J Surg. 2014;101:e119-25.

        9. Misiakos EP, Bagias G, Papadopoulos I, Danias N, Patapis P, Machairas N, et al. Early diagnosis and surgical treatment for necrotizing fasciitis:a multicenter study. Front Surg. 2017;4:5.

        10. Levett DZ, Bennett MH, Millar I. Adjunctive hyperbaric oxygen for necrotizing fasciitis. Cochrane Database Syst Rev. 2015;1:CD007937.

        11. Koch C, Hecker A, Grau V, Padberg W, Wolff M, Henrich M. Intravenous immunoglobulin in necrotizing fasciitis. A case report and review of recent literature. Ann Med Surg (Lond). 2015;4:260-3.

        12. Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing fasciitis:current concepts and review of the literature. J Am Coll Surg. 2009;208:279-88.

        13. Stevens DL, Bryant AE. Necrotizing soft-tissue infections. N Engl J Med. 2017;377:2253-65.

        14. Hawkins KL, Hoffman M, Okuyama S, Rowan SE. A case of fulminant meningococcemia:it is all in the complement. Case Rep Infect Dis. 2017;2017:6093695.

        15. Polat M, Yüksel S, Şahin NÜ. Fatal meningococcemia due to Neisseria meningitidis serogroup Y in a vaccinated child receiving eculizumab. Hum Vaccin Immunother. 2018;14:2802.

        16. Takada S, Fujiwara S, Inoue T, Kataoka Y, Hadano Y, Matsumoto K, et al. Meningococcemia in adults:a review of the literature. Intern Med. 2016;55:567-72.

        17. Medeiros I, Melo AR, Baptista V, Ribeiro A. Meningococcemia:rare but life-threatening BMJ Case Rep. 2018;2018:bcr2018226914.

        18. Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hughes JM. Meningococcal disease. N Engl J Med. 2001;344:1378-88.

        19. Campsall PA, Laupland KB, Niven DJ. Severe meningococcal infection:a review of epidemiology, diagnosis, and management. Crit Care Clin. 2013;29:393-409.

        20. Theilen U, Wilson L, Wilson G, Beattie JO, Qureshi S, Simpson D. Management of invasive meningococcal disease in children and young people:summary of SIGN guidelines. BMJ. 2008;336:1367-70.

        21. Medeiros I, Melo AR, Baptista V, Ribeiro A. Meningococcemia:rare but life-threatening BMJ Case Rep. 2018;2018:bcr2018226914.

        22. McGill F, Heyderman RS, Michael BD, Defres S, Beeching NJ, Borrow R, et al. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults. J Infect. 2016;72:405-38.

        23. The Royal Children’s Hospital Melbourne, Clinical Practice Guidelines:Acute meningococcal disease, June 2017

        24. Fidrocki D, Lutwick L. Fulminant meningococcemia. IDCases. 2017;8:17-8.

        25. Nashev D, Toshkova K, Salasia SI, Hassan AA, Lämmler C, Zschöck M. Distribution of virulence genes of Staphylococcus aureus isolated from stable nasal carriers. FEMS Microbiol Lett. 2004;233:45-52.

        26. Hanakawa Y, Schechter NM, Lin C, Garza L, Li H, Yamaguchi T, et al. Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome. J Clin Invest. 2002;110:53-60.

        27. Staiman A, Hsu DY, Silverberg JI. Epidemiology of staphylococcal scalded skin syndrome in US children. Br J Dermatol. 2018;178:704-8.

        28. Resnick SD. Staphylococcal toxin-mediated syndromes in childhood. Semin Dermatol. 1992;11:11-8.

        29. Cribier B, Piemont Y, Grosshans E. Staphylococcal scalded skin syndrome in adults:a clinical review illustrated with a new case. J Am Acad Dermatol. 1994;30:319-24.

        30. Kadam S, Tagare A, Deodhar J, Tawade Y, Pandit A. Staphylococcal scalded skin syndrome in a neonate. Indian J Pediatr. 2009;76:1074.

        31. Leung AK, Barankin B, Leong KF. Staphylococcal-scalded skin syndrome:evaluation, diagnosis, and management. World J Pediatr. 2018;14:116-20.

        32. Kouakou K, Dainguy ME, Kassi K. Staphylococcal scalded skin syndrome in neonate. Case Rep Dermatol Med. 2015;2015:901968.

        33. Amagai M, Stanley JR. Desmoglein as a target in skin disease and beyond. J Invest Dermatol. 2012;132:776-84.

        34. Blyth M, Estela C, Young AE. Severe staphylococcal scalded skin syndrome in children. Burns. 2008;34:98-103.

        35. Handler MZ, Schwartz RA. Staphylococcal scalded skin syndrome:diagnosis and management in children and adults. J Am Acad Dermatol. 2014;28:1418-23.

        36. Ladhani S, Joannou CL. Difficulties in diagnosis and management of the staphylococcal scalded skin syndrome. Pediatr Infect Dis J. 2000;19:819-21.

        37. FJ GS. Clindamycin as adjuvant therapy in Staphilococcal skin scalded syndrome. An Sist Sanit Navar. 2014;37:449-53.

        38. Braunstein I, Wanat KA, Abuabara K, McGowan KL, Yan AC, Treat JR. Antibiotic sensitivity and resistance patterns in pediatric staphylococcal scalded skin syndrome. Pediatr Dermatol. 2014;31:305-8.

        39. Mishra AK, Yadav P, Mishra A. A systemic review on staphylococcal scalded skin syndrome (SSSS):a rare and critical disease of neonates. Open Microbiol J. 2016;10:150-9.

        40. Low DE. Toxic shock syndrome:major advances in pathogenesis, but not treatment. Crit Care Clin. 2013;29:651-75.

        41. Raumanns J, Kaufhold A, Behrendt W, Peters G. Lethal, non-menstrual toxic shock syndrome associated with Staphylococcus aureus sepsis. Anaesthesist. 1995;44:869-74.

        42. Sharma H, Smith D, Turner CE, Game L, Pichon B, Hope R, et al. Clinical and molecular epidemiology of staphylococcal toxic shock syndrome in the United Kingdom. Emerg Infect Dis. 2018;24:258-66.

        43. Chuang YY, Huang YC, Lin TY. Toxic shock syndrome in children. Paediatr Drugs. 2005;7:11-25.

        44. Javouhey E, Bolze PA, Jamen C, Lina G, Badiou C, Poyart C, et al. Similarities and differences between staphylococcal and streptococcal toxic shock syndromes in children:Results from a 30-case cohort. Front Pediatr. 2018;6:360.

        45. Chen KY, Cheung M, Burgner DP, Curtis N. Toxic shock syndrome in Australian children. Arch Dis Child. 2016;101:736-40.

        46. Zimbelman J, Palmer A, Todd J. Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Pediatr Infect Dis J. 1999;18:1096-100.

        47. Sutter DE, Milburn E, Chukwuma U, Dzialowy N, Maranich AM, Hospenthal DR. Changing susceptibility of Staphylococcus aureus in a US pediatric population. Pediatrics. 2016;137:e20153099.

        48. Sriskandan S, Ferguson M, Elliot V, Faulkner L, Cohen J. Human intravenous immunoglobulin for experimental streptococcal toxic shock:bacterial clearance and modulation of inflammation. J Antimicrob Chemother. 2006;58:117-24.

        49. Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy:how does IgG modulate the immune system. Nat Rev Immunol. 2013;13:176-89.

        50. Wilkins AL, Steer AC, Smeesters PR, Curtis N. Toxic shock syndrome the seven Rs of management and treatment. Journal Infect. 2017;74:S147-52.

        51. Centers for Disease Control and Prevention, Toxic Shock Syndrome (Other Than Streptococcal) (TSS)-2011 Case Definition

        52. Colling ME, Bendapudi PK. Purpura fulminans:mechanism and management of dysregulated hemostasis. Transfus Med Rev. 2018;32:69-76.

        53. Contou D, Sonneville R, Canoui-Poitrine F, Colin G, Coudroy R, Pne F, et al. Clinical spectrum and short-term outcome of adult patients with purpura fulminans:a French multicenter retrospective cohort study. Intensive Care Med. 2018;44:1502-11.

        54. Brozyna JR, Sardia LA, Sharma A, Theil KS, Bergfeld WF. Acute purpura fulminans’a rare cause of skin necrosis:A single institution clinicopathological experience. J Cutan Pathol. 2020;47:1003-9.

        55. Lerolle N, Carlotti A, Melican K, Aubey F, Pierrot M, Diehl JL, et al. Assessment of the interplay between blood and skin vascular abnormalities in adult purpura fulminans. Am J Respir Crit Care Med. 2013;188:684-92.

        56. Chalmers E, Cooper P, Forman K, Grimley C, Khair K, Minford A, et al. Purpura fulminans:recognition, diagnosis and management Arch Dis Child. 2011;96:1066-71.

        57. Veldman A, Fischer D, Wong FY, Kreuz W, Sasse M, Eberspächer B, et al. Human protein C concentrate in the treatment of purpura fulminans:a retrospective analysis of safety and outcome in 94 pediatric patients. Crit Care. 2010;14:1-7.

        58. Rintala E, Kauppila M, SeppäläOP, Voipio-Pulkki LM, PettiläV, Rasi V, et al. Protein C substitution in sepsis-associated purpura fulminans. Crit Care Med. 2000;28:2373-8.

        59. Zarychanski R, Doucette S, Fergusson D, Roberts D, Houston DS, Sharma S, et al. Early intravenous unfractionated heparin and mortality in septic shock. Crit Care Med. 2008;36:2973-9.

        60. Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D, et al. Unfractioned heparin for treatment of sepsis:A randomized clinical trial (The HETRASE Study). Crit Care Med. 2009;37:1185-96.

        61. Smith OP, White B. Infectious purpura fulminans:diagnosis and treatment. Br J Haematol. 1999;104:202-7.

        62. Reich HL, Fadeyi DW, Naik NS, Honig PJ, Yan AC. Nonpseudomonal ecthyma gangrenosum. J Am Acad Dermatol. 2004;50:114-7.

        63. Aygencel G, Dizbay M, Sahin G. Burkholderia cepacia as a cause of ecthyma gangrenosum-like lesion. Infection. 2008;36:271-3.

        64. Leslie KS, McCann BG, Levell NJ. Candidal ecthyma gangrenosum in a patient with malnutrition. Br J Dermatol. 2005;153:847.

        65. Martínez-Longoria CA, Rosales-Solis GM, Ocampo-Garza J, Guerrero-González GA, Ocampo-Candiani J. Ecthyma gangrenosum:a report of eight cases. An Bras Dermatol. 2017;92:698-700.

        66. Mouna K, Akkari H, Faten H, Yosra K, Hichem B, Maha M, et al. Ecthyma gangrenosum caused by Escherichia coli in a previously healthy girl. Pediatr Dermatol. 2015;32:e179-80.

        67. Vaiman M, Lazarovitch T, Heller L, Lotan G. Ecthyma gangrenosum and ecthyma-like lesions. Eur J Clin Microbiol Infect Dis. 2015;34:633-9.

        68. Korte AK, Vos JM. Ecthyma gangrenosum. N Engl J Med. 2017;377:e32.

        69. Saade A, Mirouse A, Zafrani L. Ecthyma gangrenosum:An early hint for diagnosis. Int J Infect Dis. 2020;97:19-20.

        70. Sarkar S, Patra AK, Mondal M. Ecthyma gangrenosum in the periorbital region in a previously healthy immunocompetent woman without bacteremia. Indian Dermatol Online J. 2016;7:36.

        71. Khalil BA, Baillie CT, Kenny SE, Lamont GL, Turnock RR, Pizer BL, et al. Surgical strategies in the management of ecthyma gangrenosum in paediatric oncology patients. Pediatr Surg Int. 2008;24:793-7.

        72. Kracalik I, Malania L, Tsertsvadze N, Manvelyan J, Bakanidze L, Imnadze P, et al. Human cutaneous anthrax, Georgia 2010-2012. Emerg Infect Dis. 2014;20:261.

        73. Goel AK. Anthrax:a disease of biowarfare and public health importance. World J Clin Cases. 2015;3:20-33.

        74. Guarner J, Jernigan JA, Shieh WJ, Tatti K, Flannagan LM, Stephens DS, et al, Inhalational Anthrax Pathology Working Group. Pathology and pathogenesis of bioterrorism-related inhalational anthrax. Am J Pathol. 2003;163:701-9.

        75. Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith M, et al. Bioterrorism-related inhalational anthrax:the first 10 cases reported in the United States. Emerg Infect Dis. 2001;7:933.

        76. Emet M, Tortum F, Karagoz S, Calbay A. Cutaneous anthrax. J Emerg Med. 2017;52:240-1.

        77. Doganay M, Metan G, Alp E. A review of cutaneous anthrax and its outcome. J Infect Public Health. 2010;3:98-105.

        78. Ozer V, Gunaydin M, Pasli S, Aksoy F, Gunduz A. Gastrointestinal and cutaneous anthrax:Case series. Turk J Emerg Med. 2019;19:76-8.

        79. Nayak P, Sodha SV, Laserson KF, Padhi AK, Swain BK, Hossain SS, et al. A cutaneous anthrax outbreak in Koraput District of Odisha-India 2015. BMC Public Health. 2019;19:470.

        80. Suggu S, Konakanchi VC. Cutaneous anthrax in a tribal man:a case report. Postgrad Med J. 2021;97:744-5.

        81. Swartz MN. Recognition and management of anthrax an update. N Engl J Med. 2001;345:1621-6.

        82. Carucci JA, McGovern TW, Norton SA, Daniel CR, Elewski BE, Fallon-Friedlander S, et al. Cutaneous anthrax management algorithm. J Am Acad Dermatol. 2002;47:766-9.

        83. Wollenberg A. Eczema herpeticum. Chem Immunol Allergy. 2012;96:89-95.

        84. Leung DY. Why is eczema herpeticum unexpectedly rare. Antiviral Res. 2013;98:153-7.

        85. Wollenberg A, Zoch C, Wetzel S, Plewig G, Przybilla B. Predisposing factors and clinical features of eczema herpeticum:a retrospective analysis of 100 cases. J Am Acad Dermatol. 2003;49:198-205.

        86. Damour A, Garcia M, Seneschal J, Lévque N, Bodet C. Eczema herpeticum:clinical and pathophysiological aspects. Clin Rev Allergy Immunol. 2019;13:1-8.

        87. Micali G, Lacarrubba F. Eczema herpeticum. N Engl J Med. 2017;377:e9.

        88. Cooper BL. Eczema Herpeticum. J Emerg Med. 2017;53:412-3.

        89. Blanter M, Vickers J, Russo M, Safai B. Eczema herpeticum: Would you know it if you saw it?. Pediatr Emerg Care. 2015;31:586-8.

        90. Finlow C, Thomas J. Disseminated herpes simplex virus:a case of eczema herpeticum causing viral encephalitis. J R Coll Physicians Edinb. 2018;48:36-9.

        91. Wollenberg A, Wetzel S, Burgdorf WH, Haas J. Viral infections in atopic dermatitis:pathogenic aspects and clinical management. J Allergy Clin Immunol. 2003;112:667-74.

        92. Traidl S, Roesner L, Zeitvogel J, Werfel T. Eczema herpeticum in atopic dermatitis. Allergy. 2021;76:3017-27.

        93. National Institute for Health and Clinical Excellence. Atopic eczema in under 12s:diagnosis and management. Clinical guideline CG57. Last updated:02 March 2021

        94. Stefani MM, Guerra JG, Sousa AL, Costa MB, Oliveira ML, Martelli CT, et al. Potential plasma markers of type 1 and type 2 leprosy reactions:a preliminary report. BMC Inf Dis. 2009;9:75.

        95. World Health Organization. Global Strategy for further reducing the leprosy burden and sustaining leprosy control activities (2006-2010):operational guidelines. WHO Regional Office for South-East Asia;2006. Lepr Rev. 2006 Sep;77:IX, X, 1-50.

        96. World Health Organization. Guidelines for the diagnosis, treatment and prevention of leprosy;2018

        97. Scollard DM, Smith T, Bhoopat L, Theetranont C, Rangdaeng S, Morens DM. Epidemiologic characteristics of leprosy reactions. Int J Lepr Other Mycobact Dis 1994;62:559.

        98. Scollard DM, Martelli CM, Stefani MM, de Fatima Maroja M, Villahermosa L, Pardillo F, et al. Risk factors for leprosy reactions in three endemic countries. Am J Trop Med Hyg. 2015;92:108-14.

        99. Walker SL, Lockwood DN. Leprosy type 1 (reversal) reactions and their management. Lepr Rev. 2008;79:372-86.

        100. Kahawita IP, Walker SL, Lockwood DN. Leprosy type 1 reactions and erythema nodosum leprosum. An Bras Dermatol. 2008;83:75-82.

        101. Wemambu SN, Turk JL, Waters MF, Rees RJ. Erythema nodosum leprosum:a clinical manifestation of the arthus phenomenon. The Lancet. 1969;294:933-5.

        102. Kahawita IP, Lockwood DN. Towards understanding the pathology of erythema nodosum leprosum. Trans R Soc Trop Med Hyg. 2008;102:329-37.

        103. Manandhar R, LeMaster JW, Roche PW. Risk factors for erythema nodosum leprosum. Int J Lepr Other Mycobact Dis. 1999;67:270-8.

        104. World Health Organization. WHO Guidelines for the management of severe erythema nodosum leprosum (ENL) reactions. Geneva, Switzerland:World Health Organization. 2015.

        105. Hempenstall A, Smith S, Hanson J. Leprosy in Far North Queensland:almost gone, but not to be forgotten. Med J Aust. 2019;211:182-3.

        106. Saoji V, Salodkar A. Lucio leprosy with Lucio phenomenon. Indian J Lepr. 2001;73:267-72.

        107. Sehgal VN. Lucio’s phenomenon/erythema necroticans. Int J Dermatol. 2005;44:602-5.

        108. Kaur C, Thami GP, Mohan H. Lucio phenomenon and Lucio leprosy. Clin Exp Dermatol. 2005;30:525-7.

        109. Naafs B, van Hees CL. Leprosy type 1 reaction (formerly reversal reaction). Clin Dermatol. 2016;34:37-50.

        110. Lockwood DN. Steroids in leprosy type 1 (reversal) reactions:mechanisms of action and effectiveness. Lepr Rev. 2000;71:S111-4.

        111. Lockwood DN, Darlong J, Govindharaj P, Kurian R, Sundarrao P, John AS. AZALEP a randomized controlled trial of azathioprine to treat leprosy nerve damage and Type 1 reactions in India:Main findings. PLoS Negl Trop Dis. 2017;11:e0005348.

        112. Lambert SM, Alembo DT, Nigusse SD, Yamuah LK, Walker SL, Lockwood DN. A randomized controlled double blind trial of ciclosporin versus prednisolone in the management of leprosy patients with new type 1 reaction, in Ethiopia. PLoS Negl Trop Dis. 2016;10:e0004502.

        113. Hossain D. Management of chronic neuritis with a combination regimen of lower doses prednisolone and methotrexate:a brief report. Lepr Rev. 2016;87:118-21.

        114. Costa PD, Fraga LR, Kowalski TW, Daxbacher EL, Schuler-Faccini L, Vianna FS. Erythema nodosum leprosum:update and challenges on the treatment of a neglected condition. Acta Trop. 2018;183:134-41.

        115. Kaur I, Dogra S, Narang T, De D. Comparative efficacy of thalidomide and prednisolone in the treatment of moderate to severe erythema nodosum leprosum:a randomized study. Australas J Dermatol. 2009;50:181-5.

        116. Peixoto AB, Portela PS, Leal FR, Brotas AM, Rodrigues NC. Lucio’s Phenomenon. Case study of an exceptional response to treatment exclusively with multibacillary multidrug therapy. An Bras Dermatol. 2013;88:93-6.


        Source of Support: This article has no funding source.

        Conflict of Interest: The authors have no conflict of interest to declare.

        Request permissions
        If you wish to reuse any or all of this article please use the e-mail ( to contact with publisher.

        Related Content:

        Related Articles Search Authors in