Defining and Assessing Skin Changes in Severe Acute ... · Defining and Assessing Skin Changes in...

Defining and Assessing Skin Changes inSevere Acute Malnutrition (SAM)

Sofine Heilskov, Christian Vestergaard, andMette Soendergaard Deleuran

AbstractSpecific skin changes in severe acute malnutrition have been known since theearliest publication on the subject in 1933. They vary from mild dryness orpigmentary changes to severe and widespread erosions. A common standardizedway to document the skin changes observed in severe acute malnutrition is stillunder development. Currently five specific skin changes, characteristic to severeacute malnutrition, have been identified in African children. There is no knowl-edge of the global prevalence, but most reports on severe skin affections are fromsub-Saharan countries.

The etiology is still unknown and the recommendations on treatment aremostly based on expert opinion. Skin changes in severe acute malnutrition haveproven to be a prognostic marker for the risk of death. The mortality rate forpatients treated for severe acute malnutrition is persistently high and thus the skinis a target for new treatment approaches. The skin is easily accessible foradministration of treatment and assessment and is potentially a good additionaltarget to the existing treatment protocols.

KeywordsSevere acute malnutrition (SAM) • Kwashiorkor • Marasmus • Edematous mal-nutrition • Dermatosis of Kwashiorkor • Skin changes • Dermatitis •Lichenification • Hair changes • Pigmentation disturbances • Skin scoring •SCORDoK • Prognosis

S. Heilskov (*) • C. Vestergaard • M.S. DeleuranDepartment of Dermatology, Aarhus University Hospital, Aarhus C, Denmarke-mail: [email protected]; [email protected]; [email protected]; [email protected]

# Springer International Publishing AG 2017V.R. Preedy, V.B. Patel (eds.), Handbook of Famine, Starvation, and NutrientDeprivation, https://doi.org/10.1007/978-3-319-40007-5_12-1

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mailto:[email protected]




https://doi.org/10.1007/978-3-319-40007-5_12-1

List of AbbreviationsBSA Body surface areaSCORDoK Clinical score for SAM specific skin changesEFAD Essential Fatty Acid DeficiencyHR Hazard ratioMUAC Mid Upper Arm CircumferenceF75 and F100 Milk based therapeutic dietsSAM Severe acute malnutrition

ContentsIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Etiology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Etiological Focus Areas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Diagnosis and Clinical Manifestation of SAM Specific Skin Changes . . . . . . . . . . . . . . . . . . . . . . . . . 7SAM Specific Skin Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Skin Changes in Single Nutrient Deficiencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Clinical Management Options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Prognosis and Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14Policies and Protocols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Protocol-Assessing Skin Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15Protocol-Standardized Photo Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Dictionary of Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16Summary Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Introduction

The skin is the largest organ of the body. It acts as our first-line defense againstpathogens, it contributes to the regulation of body temperature and water balance,and it is an important part of the sensory system. The skin is an important clinicaltool in accessing the health status of a patient and in the diagnosis of many illnessesthat are reflected by dermal changes.

Patients suffering from malnutrition may develop skin changes as a sign of singlenutrient deficiency. These skin changes will be referred to as single nutrient-specificskin changes. In the case of severe acute malnutrition (SAM) a patient may developcharacteristic skin changes which have not yet been attributed to one specific dietarydeficiency and these are considered unique to SAM. These characteristic skinchanges will be referred to as SAM specific skin changes. SAM-specific skin changescan be severe and widespread, and new research has found that they have prognosticvalue for the patient (Heilskov et al. 2015).

Skin changes in patients suffering from malnutrition have been described in thescientific literature since the early publications on malnutrition (Williams 1933).Despite this there is still no verified explanation to the etiological background forSAM-specific skin changes, and their impact on prognosis still needs to be further

2 S. Heilskov et al.

elucidated. Additionally, suitable treatment directed specifically against the skinchanges has yet to be explored. As skin in SAM is so poorly investigated, this is apotential focus area for improvement of the treatment of SAM and lowering of thepersistently high mortality rates. The clinical assessment of the skin is easy and thereis no need to involve expensive analytic methods. It is therefore a relevant clinicaltool to be used in low resource clinics.

The geographical distribution is not yet fully mapped, but reports on skin changestend to come from the African continent. An approach to develop a commonlanguage using dermatological terminology has only recently been published(Heilskov et al. 2015). Five different skin signs were identified as specific toSAM. These results are based on Ugandan children and therefore further investiga-tion is needed to generalize these findings on a global level.

Focus areas of this chapter are:

• Etiology and pathogenesis• Histopathology• Diagnosis and clinical manifestations of SAM specific skin changes• Review clinical management options and prognosis• Present two clinical protocols supporting proper assessment and monitoring of

the skin changes

The sparse research literature on SAM and skin affection mainly focuses onpreschool children. Therefore, most of the research cited in the current chapter isbased on study subjects of the age of 6–59 months.

Etiology and Pathogenesis

The patho-physiological background for the skin changes in SAM is poorly under-stood. The clinical manifestation of the skin changes seems to be unique to SAM.Still, descriptions of skin changes in SAM tend to highlight similarities with knownsingle nutrient deficiencies. The sparse research on the subject has focused onmechanisms in single nutrient deficiencies, but studies have not yet proven theskin changes to be connected to one nutrient alone. In patients who survive stabili-zation and who recover on therapeutic foods, rich in vitamins, minerals, and fattyacids, the result is healing of the skin changes without serious sequelae. A clinicalexample of this is shown in Figs. 1 and 2.

Etiological Focus Areas

Giving an overview, of what is known and what has yet to be explored in the searchfor an etiological explanation for the skin changes in SAM, is challenging. Astandardized characteristic, using dermatological terminology, has only recentlybeen published (Heilskov et al. 2015). This common language is only based on

Defining and Assessing Skin Changes in Severe Acute Malnutrition (SAM) 3

African children and thus needs to be generalized to other skin types and culturalsettings. Therefore, we must settle for the term “skin changes” vs. no skin changes,when considering results on the etiological research.

Edema-Specific Skin ChangesSkin changes are commonly mentioned as a clinical sign of kwashiorkor (of whichedema is a diagnostic criteria), and it has been suggested that some skin changes areonly seen in edematous SAM. This has not yet been systematically investigated. Onestudy found the three stages of bullae-erosion-desquamation to be edema specific(Heilskov et al. 2015). In etiological research, some studies have concluded thatmeasured nutrients were lower in edematous patients (Giovanni et al. 2016) and evenlower in those with skin affection (Golden and Golden 1979; Vasantha 1969;Vasantha et al. 1970; Wolff et al. 1984), suggesting that the state with edemacould proceed to skin changes.

Amino Acid DeficiencyIt has been suggested that the skin could play a role as a protein reserve, like musclesupholding the function of other tissues, during starvation (Waterlow et al. 2006). Toanswer this question more research on epidermal protein turnover, compared to othertissues during starvation, must be made.

A theory on impaired maturation of collagens and cross-linking of fibers in theskin of edematous SAM patients has been suggested. This is based on the findings ofan increased proportion of labile collagen in edematous patients. Supporting this

Fig. 1 Severe skin changes in a Ugandan patient admitted to hospital, with severe acute malnu-trition and generalized edema (a). (b) The same patient after 13 days of treatment with milk-baseddiets (F75 and F100). (c) And the patient before leaving hospital, 28 days after admission tohospital. Pictures are provided by the authors


theory, the same authors found lowered levels of both collagen and noncollagennitrogen in the skin of children with edematous SAM, compared to healthy controls,and that levels decreased with the severity of skin lesions. Furthermore, analysis ofskin from SAM patients showed decreased levels of several amino acids (proline,tyrosine, and glycine) in those with skin changes compared to those without. Thelevels of these amino acids also decreased with the severity of the skin changes.Glycine and proline being a consistent part of the triple helical structure of collagenconnect these findings to the hypothesis (Vasantha 1969; Vasantha et al. 1970).

Low availability of methionine, a sulfur-containing amino acid, has beensuggested to cause the changes in skin and hair that is seen in SAM by impairingthe creation of sulfur bonds in keratin (Roediger 1995). The connection to the sulfuramino acid has been mentioned in other studies (Jahoor et al. 2008; Jahoor 2012;Amadi et al. 2009), but the theory has not yet been properly investigated. Plasmalevels of methionine have been found to be lower in SAM patients compared tostunted controls and the lowest levels were found among those with edema(Giovanni et al. 2016).

Fig. 2 Severe skin changes in a Ugandan patient admitted to hospital, with severe acute malnu-trition (a). (b) The same patient, stabilized after 6 days of treatment with milk-based therapeutic diet(F75) and antibiotics. (c) After 23 days, the patient is shifted to F100. (d) Before leaving hospital,31 days after admission to hospital. Pictures are provided by the authors


As methionine is essential in the initiation of protein synthesis, it would besurprising if the effect of methionine depletion was restricted only to affect keratinsynthesis. Inadequate amounts of methionine should theoretically affect stability ofsecondary and tertiary protein structures in general. Furthermore, as part of thecoenzyme s-adenosyl methionine, methionine depletion would have effect on theregulation of several metabolic processes.

Skin changes did play a central role in a study on dogs fed a diet devoid ofmethionine. Apart from weight loss and anorexia, the study subjects showed evi-dence of a marked dermatitis (Milner 1979).

Fatty AcidsEssential fatty acid deficiency (EFAD) is accompanied by dry and scaly skin (Collinset al. 1971). Severe cases show weeping erosions in the flexural folds (Braun-Falcoet al. 2009). A study of whole blood samples from children with SAM showed adifferent fatty acid balance compared to healthy controls. This included a lower n-6:n-3 ratio in the SAM patients. Arachidonic acid levels have been found to be lower inedematous SAM compared to nonedematous patients (Leichsenring et al. 1995;Wolff et al. 1984) and to be highly correlated with the presence of skin changes(Wolff et al. 1984). Animal models studying EFAD have shown that an impairedcutaneous permeability barrier due to EFAD causes a 50% increase in DNA synthe-sis of the skin, reflecting epidermal hyper proliferation (Proksch et al. 1991). This isin contrast to findings of lowered total protein and DNA content of the hair, inmalnourished patients (Bradfield 1972).

Niacin Deficiency (B3)Skin changes in SAM have been suggested to be a variant of pellagra caused by niacindeficiency (Stannus 1935). The skin changes in pellagra forms a symmetrical, sharplybordered erythema developing into exudative eruptions restricted to sun exposedareas such as hands and neck (Casal’s neckless) (Hegyi et al. 2004). Other clinicalfeatures of pellagra such as diarrhea are common clinical features in fulminant SAM.The mood changes seen in children with SAM could also be a clinical expression ofthe dementia seen in pellagra. This thesis has not yet been confirmed in a clinicalsetting where the skin changes are successfully treated with nicotinic acid (Ground1957; Trowell 1954). One study found decreased urinary excretion of N1-methylni-cotinamide, compatible with pellagra, in seven out of nine adults with various degreesof malnutrition and additional skin changes of lower extremities (Maltos et al. 2015).

In a recent publication serum, tryptophan levels were found to be decreased inpatients with edematous SAM (kwashiorkor) compared to those with nonedematousSAM (marasmus). This difference was one of the ten most distinguishing featureswhen comparing the two patient groups (Giovanni et al. 2016).

Deficiency of other vitamins in the B group has not yet been investigated.

Zinc DeficiencyIn acrodermatitis enteropathica, where the intestinal absorption of zinc is impaired,the isolated consequences of zinc deficiency can be seen. Dermatological features


are dermatitis, xerosis, and alopecia evolving into crusty and sharply demarcatederosions. Other symptoms are stunting, diarrhea, anorexia, and impaired cognitivefunction. All of which are features observed in SAM. Low plasma levels of zinc havebeen described in edematous SAM. In this study, an insignificant tendency for lowerlevels among patients with skin changes was noted (Golden and Golden 1979).

Histopathology

There are only few studies on the histo-pathological changes of SAM, but theyconsistently describe an epidermis with changes of parakeratosis and acanthosisindicating a rapid cell turn-over. The dermis show changes characteristic of inflam-mation with papillary edema and a tendency to lymphocytic inflammation. Table 1gives an overview of the histological cohort studies in SAM (Rangam et al. 1962;Sims 1968; Thavaraj and Sesikeran 1989).

Diagnosis and Clinical Manifestation of SAM Specific SkinChanges

Skin assessment is performed on admission to hospital. When a patient with SAMpresents with skin changes, it is to be considered as SAM with medical complica-tions (see treatment).

The patient must be naked to estimate the body surface area (BSA) affected. Aphoto protocol can be used to monitor the skin status during treatment and as a toolfor registration of data in research setups (Protocol, Fig. 10).

Setting:

• Ensure warm room temperature to avoid hypothermia• Ensure privacy• Ensure involvement of the caretaker when assessing a child• Involve a local healthcare staff as assistant, if you cannot speak the local language

SAM Specific Skin Changes

Five specific skin changes in SAM have been identified, in a recent dermatologicalpublication on skin changes in Ugandan preschool children (Heilskov et al. 2015):

• Telogenic effluvium• Pigmentary changes (hyper- and hypopigmentation)• Ichthyosiform skin changes (grade 1–3)• Lichenoid skin changes (grade 1–3)• Various stages of bullae, erosions, and desquamation (grade 1–3)


The clinical manifestation can be a mixture of the five skin changes (Fig. 3).Therefore, the systematic clinical score for SAM specific skin changes, SCORDoK(Protocol, Fig. 9), can be used to standardize the registration of the skin changes.

Table 1 Overview of histological findings in biopsy material from skin in severe acute malnutri-tion. First published in JEADV 2014 (Heilskov et al. 2014) (With permission from publisher.Licence number 3933660523976)

Study Epidermal findings Dermal findingsStudy subjects andmaterial

(Rangam etal. 1962)cohort study

In areas of athrophy, theentire thickness exist ofstratum granulosum and -lucida and there are nokerato-hyaline granula

Papillary layer showsoedematous thickening,separation of fibrils andfragmentation

31 African children

Oedematousmalnutrition

Increase in alkalinephosphatase. Placed in aband-like appearence instratum basale and -spinosum

Generalized infiltrationof histocytes, especiallyin the papillary layer

Biopsy from crusand lateral abdomen

Displacement of cells andloss of cohesion in the basallayer

Elastic fibres showfragmentation andclumping

Light microscopy

Few sweat andsebaceous glands

(Sims 1968)cohort study

Reduced overall thickness No observations 15 Zulu children,Durban

Reduced thickness ofstratum corneum

Oedematousmalnutrition

Reduced thickness of reteMalpighi (basale,spinosum, granulosum)

Biopsy from medialside of the axilla.Area with no visibleskin affection

Reduced length ofdesmosomes

Electron- and lightmicroscopy

(ThavarajandSesikeran1989) cohortstudy

Exaggeration of stratumcorneum

Atrophy of hair bulbs 20 African children

Atrophy of stratumgranulosum and -spinosum

Mixed oedematousand non-oedematousmalnutrition

In subjects with dermaloedema collagen wasreduced and there wascrowding of elastic fibres

Biopsy from lessaffected areas

Light microscopy


The presence of lichenoid skin changes has shown to be an independent predictorof death and the hazard ratio (HR) increases with severity of the lesions (Heilskov etal. 2015).

Telogenic EffluviumTelogenic effluvium is loss of telogen hair caused by a disturbed hair cycle (Fig. 4).This can vary from mild thinning to total hair loss. Telogen hairs are in a preserved

Fig. 3 Features in skin changes, related to severe acute malnutrition, on admission to hospital.Severe acute malnourished Ugandan child, complicated by oedema and severe skin involvementwith mixed skin changes: Lichenoid skin changes grade 3 and bullae, erosions and desquamationgrade 2. Hyperpigmentation is seen in relation to lichen and erosions. Scalp hair has been razed of.Pictures are provided by the authors


state of rest opposite to growing hairs in the anagen phase. During research on hair, itwas noted that the hair was easier pulled out in malnourished patients. The hair bulbshad a smaller diameter and this was directly related to a lower weight for age. Ahigher proportion of hair bulbs were in the resting state (telogen phase) in the case ofmalnutrition (Bradfield et al. 1968). Telogenic effluvium is known to be secondary tochanges in several physiological mechanisms that are expected to be compromisedin SAM and related to co-morbidities such as infections (Braun-Falco et al. 2009).

SAM-related telogenic effluvium is often combined with depigmentation and/orstraightening of curly hair. The flag sign, where light bands in the hair reflect thenutritional status of a child over time, can be observed. Changes in hair status areconnected to hair cycle and thus are slow. It takes 2–5 months before a telogen hair isshed, after the shift from the anagen phase. Telogenic effluvium is therefore expectedto be a sign of more chronic malnutrition. It has also been noticed that changes in thestatus of the hair are not seen during the short time of recovery from SAM in ahospital (Heilskov et al. 2015).

Pigmentary ChangesPigmentary changes (Fig. 5) are hyper- and hypopigmentation. The change inpigmentation can be general, as seen in systemic disease, or well-defined areas. InSAM, pigmentary changes often follow the other SAM-specific skin changes but canbe the only skin change in a SAM patient.

Ichthyosiform Skin ChangesIchthyosis is generalized scaling of the skin and is histologically characterized byhyperkeratosis. Ichthyosis can be coupled to the protein synthesis of thekeratinocytes, as in ichthyosis vulgaris, or the lipid components of the extra-cellularmatrix, as in X-linked recessive ichthyosis, both resulting in retention

Fig. 4 Telogenic effluvium. Various manifestations of increased telogenic effluvium, also showingdepigmentation and straightening of the hair (a, b, c). First published in JEADV 2015 (Heilskov etal. 2015) (With permission from publisher. Licence number: 3,933,580,522,015)


hyperkeratosis, which is abnormal shedding of the corneal layer (Braun-Falco et al.2009; Williams 1992). Grades of affection in ichthyosiform skin changes in SAMare shown in Fig. 6.

Grade 1 is characterized by dry skin, hyperpigmentation, and accentuation of thelines of the skin. Mild shedding of fine grey scales is observed in few areas. In grade2, the dark skin turns greyish and the dusty scales loosen easily. Areas withhyperkeratosis appear. In these areas, the scales are more infiltrated and bigger. Ingrade 3 scales are hard, shiny, and slightly hyperpigmented. Erosions appear wherethe scales are shed.

Fig. 5 Pigmentary changes. Pigmentary changes in SAM. Hypopigmentation caused by desqua-mation (a, b) and erosion (b, c) and hyperpigmentation in lichenoid skin changes (c). Firstpublished in JEADV 2015 (Heilskov et al. 2015)( With permission from publisher. Licence number:3,933,580,522,015)

Fig. 6 Ichthyosiform skin changes. Grades of affection in ichthyosiform skin changes on extrem-ities. Grade 1 (a), grade 2 (b), grade 3 (c). First published in JEADV 2015 (Heilskov et al. 2015)(With permission from publisher. Licence number: 3,933,580,522,015)


Lichenoid Skin ChangesLichenoid skin change is a term for skin changes that clinically resemble theprototype lichen planus. Lichen is noninfectious and is histologically characterizedby lymphocytic infiltrate at the epidermal function forming a band-like pattern.Papules tend to fuse into flat-topped patches bordered by the skin lines. There aremany clinically variants of lichen.

In research on SAM, no authors have commented on pruritus, but a distribution ofthe skin changes to areas of mechanical stress rather than sun-exposed areas has beennoted (Heilskov et al. 2014). Grades of affection in lichenoid skin changes in SAMare shown in Fig. 7.

Grade 1 is characterized by small (�0.5 cm) papules. These are hyperpigmentedand irregular on the surface but not hyperkeratotic. The smallest (1–2 mm) arepurple-brown. In grade 2, the areas affected are bigger and coalesce to highlyhyperpigmented plaques of various sizes. These can be hyperkeratotic and thelines of the skin are accentuated. The border is irregular, but well defined and inthese areas, the original papules can be identified. Plaques can loosen and peel off. Ingrade 3, the plaques are more infiltrated and rigid and the surface can be shiny.Plaques peel off leaving thin epidermis or erosions. The whole body can be affected,but palms and soles are spared.

Bullae, Erosions, and DesquamationA bulla is a raised circumscribed lesion containing serous fluid and measuring>5 mm. The involved layers of the epidermis can vary and no histological researchhas yet been made concerning the bullae in SAM. A bulla tends to rupture and theouter layer desquamates from the skin, leaving the epidermis exposed as an erosion.An example of bullae, erosions, and desquamation in SAM is shown in Fig. 8. As theerosions affect primarily the epidermis, it tends to heal without scarring.

Fig. 7 Lichenoid skin changes. Grades of affection in lichenoid skin changes. Grade 1 (a), grade 2(b), grade 3 (c). First published in JEADV 2015 (Heilskov et al. 2015) (With permission frompublisher. Licence number: 3,933,580,522,015)


Severity grade of this SAM-specific skin change is defined by the affected BSA.Bullae, erosions, and/or desquamation is observed on the body, affecting<5% of thebody in grade 1, from 5 to 30% in grade 2 and more than 30% in a grade 3. The cut-off values for grade of affection are not based on experience on outcome orinvestigation on prognosis.

Differential Diagnosis

Burns, diaper dermatitis, atopic eczema, staphylococcal scalded skin syndrome(SSSS), and skin changes due to a single nutrient deficiency.

Skin Changes in Single Nutrient Deficiencies

Amalnourished patient is most likely to be lacking several vitamins that are importantfor maintenance of healthy skin. Still the clinical skin manifestation can be dominatedby the signs of a single nutrient deficiency of which niacin (B3), zinc, some aminoacids, and essential fatty acids have been described. The fat-soluble vitamin A, water-soluble riboflavin (B2), pyridoxine (B6), and vitamin C and biotin are also connected toskin and mucosal changes. The diagnosis of the single nutrient deficiencies, based onclinical findings, is difficult as the clinical appearance is often less characteristic.

Clinical Management Options

Skin changes in SAM account for one criterion of complicated SAM and thesepatients are preferably referred to hospital care. There are currently few well-documented recommendations on treatment of skin changes in SAM.

Fig. 8 Bulla, erosion and desquamation. Bullae, erosions and desquamation on lower extremities(a, b, c). First published in JEADV 2015 (Heilskov et al. 2015) (With permission from publisher.Licence number: 3,933,580,522,015)


Recommendations on treatment of SAM complicated by skin changes are summa-rized in Table 2 (Ashworth 2005; Ashworth et al. 2003; Golden and Grellety 2012;Golden et al. 1980; Salam et al. 2013; WHO 2013; WHO and UNICEF 2009).

Prognosis and Complications

Complicated SAM has a high mortality rate even when being managed in hospital.Known complications in SAM that theoretically can be related to a broken skinbarrier are hypothermia, dehydration, electrolyte imbalance, and infection/sepsis.

Three studies have confirmed skin changes to be a predictor of death (Becker etal. 2005; Heilskov et al. 2015; McLaren et al. 1969). In a characteristic of specificskin changes in SAM, it was found that lichenoid skin changes significantly loweredthe chance of survival and that the HR increased with the grade of severity (Table 3)(Heilskov et al. 2015). It was also revealed that lichenoid skin changes could be usedin a logistic regression model, to forecast death when admitting SAM patients tohospital. The misclassification error of the model, constructed of known risk factors,was improved when adding lichenoid skin changes as a variable.

Table 2 Focus areas in the hospital treatment of skin changes, complicating severe acutemalnutrition

Milk based therapeutic food (Ashworth etal. 2003; WHO and UNICEF 2009).

Admission and stabilisation: F75, containing75 kcal/100 ml and 0.9 g protein/100 ml.

After stabilisation: F100, containing100 kcal and2.9 g protein/100 ml.

Give the food orally ore use nasogastric tube. Neverparenteral substitutes.

Encourage continued breastfeeding.

Possible regimes for topical treatment(Ashworth 2005; Ashworth et al. 2003).

Zinc (Golden et al. 1980) and castor oil ointment, orpetroleum jelly or paraffin gauze) to raw areas.

Soak the affected areas for 10 min/day in 0.01%potassium permanganate solution. Disadvantagesof this regime has been discussed (Golden andGrellety 2012).

Application of oils rich in essential fatty acids, likesunflower seed oil (linoleic acids) has proven toapprove skin barrier function, enhance weight gainand lower the risk of skin infection in preterminfants (Salam et al. 2013). This regime is for ulcer-free skin affections and is, for now, to be consideredas a low-cost alternative to the above mentioned.

Antibiotics (Ashworth 2005; WHO 2013;WHO and UNICEF 2009).

Gentamicin IVor IM (7.5 mg/kg), once daily for7 days, plus ampicillin IV or IM (50 mg/kg), every6 h for 2 days.

Followed by amoxicillin oral (15 mg/kg), every 8 hfor 5 days.


Policies and Protocols

Protocol-Assessing Skin Status

Standardized Clinical Score of Skin manifestations in SAM-SCORDoKComparability of results and objectivity in registration are important factors whenreporting research results. This protocol is a tool for registration of the characteristicskin changes in SAM, with an estimate of severity and affected BSA.

Setting:

• It is important to have sufficient light in order to evaluate the skin changes.• Ensure warm room temperature to avoid hypothermia.

Table 3 P-values from Cox-regression for correlation between six skin predictors and risk of death(hazard). From the table, it is seen that lichenoid skin changes significantly lower the chance ofsurvival and that the risk of death relative to healthy controls, increase with the grade of severity(hazard rate, HR) Data are from JEADV 2015 (Heilskov et al. 2015) (With permission frompublisher. Licence number: 3,933,580,522,015)

PredictorHazardratio

Unadjustedmodel (0/1)

Adjustedmodel (0/1)a

Unadjustedmodel (grade0–3)

Adjustedmodel (grade0–3)a

[HR] [P] [P] [P] [P]

Telogeniceffluviumb

0,65 0,64 0,58 – –

Pigmentarychangesb

1,26 0,42 0,73 – –

Ichthyosiform skinchanges^

– – – –

Lichenoid skinchanges

0,34 0,23 0,03 0,02

Grade 1 ^Grade 2 6,00

Grade 3 13,79

Bullae – erosions –desquamation

0,30 0,38 0,09 0,35

Grade 1 ^Grade 2 2,65

Grade 3 3,22

Body surface areac – – – 0,30 0,42aAdjusted for age, sex and oedemabTelogenic effluvium and pigmentary changes are both dichotomous (1/0) variables and there aretherefore no p-value for these as graded predictorscBody surface area is a continuous predictor (0–100%) and therefore there is no p-value for astratified analysis.^ no events observed


• Ensure privacy.• Ensure involvement of the caretaker when assessing a child.• Involve a local healthcare staff as assistant, if you cannot speak the local language.

Figure 9 below is a guide to register the SAM-specific skin changes and toestimate affected BSA in preschool children. Be aware that the BSA distribution isdifferent in adults, children, and babies.

Protocol-Standardized Photo Protocol

Photography is traditionally used in the dermatological field for reporting andregistering skin changes.

This photo protocol is a practical tool to monitor the development of the skinchanges during treatment and when monitoring intervention.

A good picture protocol is also an advisable supplementation to a study setup, toensure objectivity and when later assessing intra- and interobserver variability.Dermatologists are often not available in developing countries and the use of photosin telemedicine requires standardized picture of good quality.

Setting:

• Assure informed consent before taking pictures• Use a camera of good quality• Establish good light and a matt colored background• Ensure warm room temperature to avoid hypothermia• Ensure privacy• Ensure involvement of the caretaker when assessing a child• Use the assistance of a local healthcare staff, if you cannot speak the local

language

A guide to a systematic photo protocol, using the preschool child as an example,is shown below (Fig. 10).

Dictionary of Terms

Severe acute malnutrition It is the acute form of malnutrition usually affectingchildren and is characterized by low weight forheight (wasting) or bilateral pitting edema. Thediagnosis is supported by anthropometric measuresand a history of insufficient food intake.

Body surface area It is widely used in the dermatology to reflect thegrade of affection in skin disease. Best known is


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the “Rule of Nines” chart, used in the assessmentof skin damage from burns.

Mortality rate It is a measure of deaths per unit time, in a givenpopulation.

Hazard ratio It is used in survival analysis to reflect the risk ofdeath in a study cohort relative to a control group.If the treated cohort has a mortality rate twice ashigh than the control group, the hazard ratio equals2. A hazard ratio > 1 indicates increased risk ofdeath in the cohort.

TruncusOverview

Lower extremities and Gluteal region Anal region Inguinal region

Axilla and Upper extremities

Face an Scalp

Focus on body surface area

Let caretaker hold thechild while standing

Extensor side Close-up on nails

Focus on mouth. nose andeyes

Focus on scalp, ears and hairRemember to look behind

earsAxilla and Flexorside

Fig. 10 Guide to standardised photo documentation when monitoring the skin changes in severeacute malnutrition. # Copyrighted all rights reserved. Copyright number: TXu 1–948-432. Editedby Asbjoern Axelsen. First published in JEADV 2015 (Heilskov et al. 2015) (With permission frompublisher.Licence number: 3,933,580,522,015)


Logistic regression model It estimates a probability of an outcome, for exam-ple death. It is based on binary variables and givesthe opportunity to conclude whether the presenceof a variable increases the risk of the currentoutcome.

Summary Points

• This chapter focuses on characteristic skin changes in severe acute malnutrition.• The sparse research on the subject has focused on mechanisms in single nutrient

deficiencies, but studies have not yet proven the skin changes to be connected toone nutrient alone.

• Focus areas in the etiological research have been amino acid deficiency, essentialfatty acid deficiency, niacin deficiency (B3), and zinc deficiency.

• Five skin changes have been identified as specific to severe acute malnutrition(telogenic effluvium, pigmentary changes, ichthyosiform skin changes, lichenoidskin changes and stages of bullae, erosions, and desquamation).

• Skin changes in severe acute malnutrition can be severe and comprehensive andresearch has found that they increased risk of death if present.

• Lichenoid skin changes significantly lower the chance of survival and the hazardratio increases with the grade of severity.

• Skin changes in severe acute malnutrition are one criterion of complicated severeacute malnutrition, and these patients are preferably referred to hospital care forintravenous therapy with antibiotics, in addition to therapeutic feeding.

• The standardized clinical score of skin manifestations in severe acute malnutri-tion, SCORDoK, ensures a standardized system to monitor the skin duringtreatment and secure comparability of results when reporting researchobservations.

• A photo protocol is a practical tool to monitor the development of the skinchanges during treatment, when monitoring intervention, and is essential intele-medical communication.

• The etiology of the skin changes is unknown and suitable treatment, based onresearch results, has yet to be developed.

• The epidermis has changes of parakeratosis and acanthosis indicating a rapid cellturn-over.

• The dermis show changes characteristic of inflammation with papillary edemaand a tendency to lymphocytic inflammation.

• The geographical distribution is not yet mapped out but reports on skin changestend to come from the African continent.


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