inflammatory agents that function in recruiting monocytes and macrophages to the site of injury,

indicating sustained inflammation throughout the wound healing process. Furthermore, MCP-1 has also

been implicated in bone remodeling and may be an earlier indicator of HO development. Locally,

proinflammatory cytokine MIP-1 alpha has been shown to be upregulated, indicating robust

inflammation locally. This inflammatory response is believed to enhance bone regeneration; however,

the precise cells and cytokines involved for this enhanced osteogenesis remain unknown. Studies have

shed some light into what might contribute to this enhanced osteogenesis. RUNX2 has been shown to

increase in the presence of macrophages and inflammatory cytokines and this increased expression

results in an increase in bone mineralization.137 Other studies have demonstrated an increase in the

tumor necrosis factor family and ILs, including IL-1, IL6, IL-8, IL-10, IL12, and IL-18.139

The most recent work in this field has focused on BMP signaling as a central mechanism that leads to

ectopic bone formation. Early studies demonstrated that inhibition of transcriptional activity of BMP

type I receptors with antagonists such as noggin and chordin has been shown to disrupt the osteoblast

differentiation signaling pathways.139,140 Mice lacking noggin showed overactivity of BMP and

displayed HO. The role of BMP signaling as an important regulator of ectopic bone formation, along

with other mediators such as PDGF, insulin-like growth factor 1 (IGF-1), and TGF-beta1, continues to be

the focus of research. Identifying pharmacologic therapies that inhibit the overactive inflammatory

response may inhibit the development of HO.141

Additional studies have focused on the identification of progenitor cells responsible for HO. Nesti et

al.140 identified and isolated a population of multilineage mesenchymal stem cells with osteogenic

potential that were localized primarily in traumatized tissue. Mesenchymal stem cells are multipotent,

adult progenitor cells of great interest because of their unique immunologic properties and regenerative

potential.142 These progenitor cells have been shown to promote wound healing and regeneration of

surround tissues by migrating to the site of injury, promoting repair and regeneration of damaged

tissue, modulate the immune and inflammatory response, and secrete trophic factors that are important

in wound healing and tissue remodeling.142–146 Tissue resident progenitor cells are known to be highly

sensitive to the surrounding inflammatory milieu.147,148 Interestingly, a study by Wu et al.149 indicates

that exposure of skeletal muscle satellite cells to the serum of burned rats is sufficient to promote their

osteogenic differentiation, suggesting that both systemic and local inflammations may play a role in

driving stem cell differentiation. In addition, studies have recently shown that burn injury promotes HO

of adipose-derived stem cells in a murine model of scald injury. Microcomputed tomography and

histologic analysis demonstrated increased endochondral ossification in the burn group compared to the

sham control, a process which was most likely mediated through increased vascularization.150 While

resident mesenchymal stem cells seem to be implicated in the pathogenesis of HO, there is reason to

believe that the immunomodulatory properties of these cells may be activated to suppress the

proinflammatory microenvironment when applied externally.151 Further studies are necessary to fully

elucidate the therapeutic utility of these cells.

Other groups have shown that these mesenchymal progenitor cells can be isolated from both health

and traumatized muscles. Both health and traumatized muscles have osteoprogenitor cells that have the

potential to form ectopic bone after injury.140 Laboratories have suggested that cells responsible for HO

are from the endothelium of the local vasculature.152 These studies suggest that in a setting of

chronically stimulated BMP activity, muscle injury and associated inflammation sufficiently trigger

heterotopic bone formation and that cells of vascular origin are essential to the development of ectopic

bone. This cell lineage, along with stimulating factors such as BMP that create the correct environment

for bone formation, could be target for the development of therapeutic interventions to treat HO.153

Further understanding the signaling pathways and the involvement of MSC differentiation is essential

for the development of early diagnostic and prognostic tests and the development of novel prophylactic

therapies.

REHABILITATION

In addition to an increased need for reconstructive surgery secondary to increased survival, there is also

an increased need to focus on functional, social, and psychological rehabilitation. The National Institute

of Disability and Rehabilitation Research (NIDRR) has continued to fund multi-institutional research to

better understand long-term rehabilitative outcomes and needs. Therapists must play an integral role of

inpatient and follow-up care. Inpatient care should include aggressive splinting and range of motion. As

patients transition to discharge, therapists should work on strengthening, performing activities of daily

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living, and occupational guidance.

NONBURN CONDITIONS COMMONLY CARED FOR IN BURN

CENTERS

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis syndrome (TENS) have widespread

necrosis of the superficial portion of the epidermis (Fig. 12-14). SJS/TEN is commonly associated with

sulfonamides, trimethoprim-sulfamethoxazole, oxican NSAIDs, chlormezanone, and carbamazepine.

However, a single offending drug is identified in less than 50% of cases. Antibiotic-associated SJS/TEN

presents ~7 days after drug is first taken whereas anticonvulsant-associated SJS/TES can present up to 2

months after drug is first taken. TEN can also be caused by staphylococcal infections in

immunocompromised patients. In general SJS total involvement is defined as less than 10% TBSA with

widespread erythematous or purpuric macules or flat atypical targets are present. TEN has total

cutaneous involvement of greater than 30% TBSA and SJS-TENS overlap involves 10% to 30%. Given

the difficulty distinguishing these from drug eruptions we recommend a biopsy be sent. This biopsy is

also crucial for treatment as steroids are often recommended for drug eruptions but they have not been

shown to improve outcomes in patients with SJS and TENS. It is crucial in these patients to assess the

oral, opthalmologic, and urogenital mucosa. Oral mucosal involvement can create a difficult airway as

the difficult airway team should be present if intubation is necessary. We recommend aggressive

lubrication of the periorbita and an ophthalmology consult if the eyes are involved and OB/Gyn should

be consulted for vaginal mucosal involvement. Treatment of the skin sloughing should include a

nonstick silver impregnated gauze. If large skin involvement we typically use acticoat. Some centers,

however, have demonstrated success with xenograft treatment of large open areas. Currently the data

do not support steroid or intravenous immunoglobulin (IVIG) treatment.

Figure 12-14. Stevens–Johnson syndrome and toxic epidermal necrolysis syndrome.

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Figure 12-15. Ischemia of the extremities leading to amputation.

Staph scalded skin syndrome has a similar skin appearance to TENS except that it also has positive

blood cultures. These wounds are usually more superficial than TEN and the mucosa and conjunctiva are

typically not involved. Patients should receive empiric and subsequently culture-based

antistaphylococcal antibiotics.

Purpura fulminans often presents after streptococcal or meningococcal sepsis. These patients often

have multisystem organ failure secondary to septic shock and vasopressive treatments for

cardiovascular support. Patients often suffer from ischemia of the extremities. Treatment of the wounds

should be supportive until the patient is stable enough for a definitive operation. Given that tissue death

occurs from ischemia, these patients often require amputations (Fig. 12-15).

CONCLUSION

Burns are responsible for significant morbidity and mortality and are among the most complex and

devastating of all traumatic injuries. Early proper diagnosis of burn depth and extent allows for the

delivery of appropriate treatment ensures the best prognosis for burn patients. Early tangential excision

and autografting remain the foundation of burn treatment. New technologies have advanced the method

of diagnosis from punch biopsies to less invasive imaging studies. Diagnosis of secondary burn

complications, such as joint contracture and HO, has also advanced with new imaging tools, such as the

Raman spectroscopy, that may allow for earlier detection and treatment of ectopic bone formation. The

management of burn patients requires a team of physicians, nurses, critical care specialists, physical

therapists, and counselor to provide optimal care to patients and lessen the burden of the initial burn

injury. Novel clinical, basic science, and translational science researches continue to improve our

understanding of the pathophysiology of burn injuries. By elucidating the pathophysiology of both the

primary wound and secondary complications will assist in the treatment during the critical period and

following the initial trauma and prevent secondary burn complications.

APPENDIX

Burn Resuscitation Flowsheet

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