The Skin in systemic diseases

The Skin in commonly encountered systemic diseasesLiver diseaseRenal diseaseInternal malignancyDiabetes

The skin in liver diseasePruritusAlways suspect systemic disease when patients complain of pruritis, follow through with basic screening investigations, including liver profile

Nearly any liver disease, but the most commonly associated entities are primary biliary cirrhosis, primary sclerosing cholangitis, obstructive choledocholithiasis, carcinoma of the bile duct, cholestasis

bile acids that deposit into the skin is responsible for the pruritus, though levels dont correlate with severity

2The skin liver diseaseDiffuse hyperpigmentation of the skin

The exact Mechanism unknown

Suspected presence of increased amounts of melanin, widely dispersed throughout both epidermis and dermis

Moreso in PBC and Haemochromatosis( melanin and iron)

3The skin in Liver diseaseSpider Naevican be benign, seen in pregnancy , estrogen therapy, and thyrotoxicosis

central red arteriole, or punctum, surrounded by a radial pattern of thin-walled capillaries,

Compression of the central vessel results in blanching

frequently found on exposed areas of the body especially the upper half of the trunk such as the face, neck, upper trunk

4The skin in Liver diseasePalmar ErythemaIt may also be a normal finding.

reddening of the palms of the hands affecting the thenar and hypothenar eminences.

The soles of the feet are often also affected

Other conditions include, pregnancy, thyrotoxicosis, rheumatoid arthritis, polycythaemia , chronic leukaemia, or shoulder-hand syndrome, also be the result of dermatoses such as eczema or psoriasis.

5The skin in liver diseaseWhite nails/Terry nailsCan be seen in other conditions Congestive heart failure , diabetes mellitus and Malnutrition.

Proximal paleness extending halfway up the nail,

often eliminating the lunula with a darker distal band

condition is thought to be due to a decrease in vascularity

80% liver disease patients have it

6The skin in liver diseasePorphyria cutanea tardaIncrease in porphyrins result in photosensitivitySores (erosions) following relatively minor injuriesFluid filled blisters (vesicles and bullae)Tiny cysts (milia) arising as the blisters healIncreased sensitivity to the sunAvoidance of alcohol, protection against sun,phlebotomy

most frequent type of porphyria worldwide and results from a catalytic deficiency of uroporphyrinogen decarboxylase

acquired variant, also referred to as sporadic or type I PCT

enzymatic deficiency is limited to the liver and not all tissue

significant association with liver disease that can be triggered by genetic and environmental factors, such as alcohol abuse, iron overload, haemochromatosis, polychlorinated hydrocarbons, and hepatitis C virus infection7The skin in Liver diseaseXanthomaXanthelesma- Occur in the peri orbital areas as yellowish polygonal plaques or papulesEruptive xanthoma- Seen on extensor surfaces as dome shaped red papules

lesions characterized by accumulations of lipid-laden macrophages.

develop in the setting of altered systemic lipid metabolism

Seen more in PBC8The skin in Renal diseaseAcquired perforating dermatosis Extensor surface and extremities of trunkIn addition to CRF seen also in DM, liver disease and thyroid disease

Rx with- Emolient and Anti histamine to relieve pruritisOther RX High dose Vitamin A, Isoretinoin

Rx underlying CKD

small papules ,

pruritic that

eventually grow to about 1.5cm in diameter to form red-brown nodules with a central keratin (horny) plug

More commonly seen in the ESRD spectrum9The skin in renal diseaseCalciphylaxislong-standing history of chronic renal failuregenerally occur on the lower extremitiesliver disease, diabetes, hypercalcemia and hyperphosphatemia and treatment with warfarin

Aetiogenesis Calcification blocks small blood vessels deep in the skin, resulting in spreading skin necrosis

developed lesions have a stellate purpuric configuration with central cutaneous necrosis Follow the path of vasculature

Rx The initial step is to normalise the calcium and phosphate product levels, and control the hyperphosphatemia associated with renal failure. A calcium and phosphate restricted diet and dialysis with a lower diasylate calcium concentration is important initial management in the calciphylaxis associated with renal failure

If PTH is high , surgery maybe warrantedsodium thiosulfate, an antioxidant and chelator, has also been used successfully to remove the calcium. Healing occurs slowly over weaks to months.

10The skin in renal diseasePruritisSystemic treatments that have been used in UP include ultraviolet light, gabapentin, opioid receptor antagonists and agonists, antihistamines, activated charcoal, 5-HT3antagonists, immunomodulators and erythropoietin.Topical- Emolient, capsacin for localized use

Complex mechanism CRF fails to excrete mediators associatedwith pruritis immunohypothesis considers UP to be an inflammatory systemic disease rather than a local skin disorderOpioid hypothesis with over expression of opioid U- receptors

Facilitated by dry skin, Also be increased dermal mast cells which release histamine, Anemia

11The skin in renal diseaseHyperpigmentationattributed to an increase in melanin in the basal layer and superficial dermis due to failure of the kidneys to excrete beta-melanocyte-stimulating hormone (b-MSH)cutaneous pigmentation, in particular macular hyperpigmentation of the palms and soles, and diffuse hyperpigmentations of the mucosal membranes, can be seen relatively early

A yellowish tinge can be seen, It has been attributed to the accumulation of carotenoids and nitrogenous pigments (urochromes) in the dermis

12The skin in renal diseaseHalf and half nail/Lindsay nailsThere is no correlation between the degree of azotemia and the percentage of nail bed that is occupied. There is no specific therapy

Distal brown transverse band

The proximal white band is thought to result from chronic anemia and the brown band from increased melanin deposition distally, possibly from an increased concentration of -melanocytestimulating hormone.

13The skin in renal diseasePseudoporphyriaPseudoporphyria describes a bullous photosensitivity that clinically and histologically mimics porphyria cutanea tarda.

However, no demonstrable porphyrin abnormalities are present.. serum/plasma porphyrin assay. If this result is negative,

In addition to CRF treated with HD it is also seen in those with excessive exposure to ultraviolet A (UV-A)and numerous drugs( NSAIDS/Antibiotics/Antiarrythmics/Diuretics etc)

14The skin in renal diseaseUremic frost.

Uremic frost is an uncommon dermatologic manifestation of profound azotemia and occurs when urea and other nitrogenous waste products accumulate in sweat and crystallize after evaporation15The skin hyperlipidemia

The skin in hyperlipidemiaXanthelesma Palpebrum Soft plaques on eyelidsMost common variantTreatment options include laser therapy, electrodessication followed by curettage

Once plaques are established, they will remain static or increase in size so aesthetically problematic

no evidence that lipid lowering treatment has any impact on the appearance of xanthelasma

Also can be seen following erythroderma

17Skin in hyperlipidemiaTuberous xanthomaFirm, painless, red-yellow nodules that develop around the pressure areas such as the knees, elbows, heels and buttocksLesions can join together to form multilobated masses

Seen in type 2 and 3 HL and secondary causes DM

18The skin in hyperlipidemiaTendinous XanthomasAppear as slowly enlarging subcutaneous nodules or papules related to the tendons or ligamentsMost commonly found on the dorsum of the hands, feet, and Achilles tendonConsider familial Hypercholestrolemia and screen

Sreen in type 2, 3, and secondary

In the absence of elevated cholesterol, can occur in sitosterolemia and cerebrotendinous xanthomatosis

19The skin in hyperlipidemiaEruptive xanthomaSudden onset crops of small, yellow or yellowish brown papules encircled by an erythematous halo wax and wane according to variations in plasma ( very high) triglyceride and lipid content

Seen in secondary(DM)- poor control and Type 1, 4, 5 and

found on the buttocks, posterior thighs, knees and elbows.

20The skin in hyperlipidemiaPlanar XanthomasYellow macular areasapproximately 50% of cases occur in the absence of lipid or lipoprotein abnormalitiesWhen it occurs in the eyelids..Lesions on the creases of the palms are indicative of a specific pattern of increased lipids in blood called type III dysbetalipoproteinaemia

21MisnomersDiffuse planar xanthomaA form of histicytosis Associate with myeloma and leukemia

Xanthoma disseminatumAgain a rare form of histiocytosis

Both have normal lipid values

The Skin in Internal MalignancyAcanthosis nigricans

cutaneous sign of an underlying condition or disease.Associated with GIT based tumours- esp StomachHowever its prudent to exclude more common causes DM, HL, Obesity, syndromic- PCOS, cushings, Benign and even hereditary

Thickened brown velvety textured patches of skin that may occur in any location but most commonly appear in the folds of the skin in the armpit, groin and back of the neck.Papillomatosis (multiple finger-like growths) is common on cutaneous and mucosal surfaces.Skin tags often found in and around affected areas

Lesions are deeply pigmented , rapi in onset associated with weight loss Involves atypical areas such as palms23The Skin in Internal MalignancyErythema gyratum repensPathogenesis is unknown but is thought to be mediated by tumour Ag and its interaction with skinMost common underlying causes are bronchial , oesophageal , breast

clinically distinctiveThe eruption is rapidly migrating 1cm/dayPruriticUsually precedes by about a year but can also occur following discoverycomposed of concentric rings forming a wood-grain pattern

24The Skin in Internal MalignancyAcquired hypertrichosis lanuginosaSeen in the latter part so usually poor prognosisSeen in lung , breast, uterine carcinoma

rapid growth of long, fine, lanugo-type hair particularly around the eyebrows, forehead, ears and nose.Other affected areas include trunk, axillae

25The Skin in Internal MalignancyNecrolytic Migratory erythemaSeen in glucagnoma (Alpha cell pancreas tumour)The results of excessive glucagon also include:Diabetes mellitusWeight lossDiarrhoea etc.so look and ask for these

Initially there is a ring-shaped red area that blisters, erodes and crusts over. It can be quite itchy and painful. As it heals, it may leave behind a brown mark.Has a moving crusting edgeCan affect any site, but usually genital and anal and periorificial

26The Skin in Internal MalignancyBazex syndromeAssociated with squamous cell carcinoma of the upper respiratory or gastrointestinal tract, thymus or vulva.Topical steroidsandemollient creams containingurea , lactic acid orSalycylic acid, may reduce the thickness and irritation of the scaly skin lesions.Search underlying malignancy

Severely abnormal nails with painful paronychia (swollen red nail folds) with no evidence of bacterial or fungal infection.Scaly eruptions on the external ears that may progress to involve the cheeks and noseDiffuse thickening and scaling of the palms and soles (keratoderma), with a peculiar honeycomb appearanceEventually the skin disease may spread to involve trunk, limbs and scalp

27The Skin in Internal MalignancyDermatomyositisIn the young it can be the autoimmune spectrum of the diseaseBut in the elderly > 60 years suspect MalignancyAssociated with carcinoma cervix, lung , pancreas , breast

Reddish or bluish-purple patches, mostly on sun exposed areasHeliotrope rashPurple papules s on bony prominences known as gottrons papules when its flat its gottrons signMechanics hands- rougheneing and fissuring of the skin on the plams and radial surface of the fingersShawl sign macular erythema on the posterior surface neck and shpulderOther features include proximal muscle weakness, Raynauds phenomenon and calcinosis

In adult patients with dermatomyositis, assessment for malignancy should be performed upon initial diagnosis and repeated at least annually for 3 years.

28The Skin in Internal MalignancyAcquired ichthyosis Acquired inUnderactivethyroidSarcoidosisHodgkin lymphomaHIV

characterized by small white or brownish rhomboid scales on the extensor surfaces of the extremities and on the trunkNumerous causes !!! Can grossly divide it into Inherited and acquired

29The Skin in Internal MalignancyGeneralized Pruritis

Localized pruritisGen-- T cell-dysregulation and the production of mediators such as histamine and serotoninAssociated with hodgkins lymphoma, carcinoid syndrome, Cutaneous T cell lymphoma

Local= can occur brain tumours

Brain diseases like stroke, sclerosis multiplex, abscesses, may sometimes induce severe generalized or localized pruritus30The Skin in Internal MalignancySweet syndromeAssociated with AML , haematological malignancy

sudden onset of asymmetric skin lesions on the face, the extremities, and the upper part of the trunk. multiple erythematous or violaceous papules, indurated plaques, and painful inflammatory nodules that are typically accompanied by fever, neutrophilia, and systemic alterations

31The Skin in DMNecrobiosis LipoidicaTreatment includes Steroid topical or intralesional , ciclosporin, PUVA

Incidence is 0.3% in diabetics Most being insulin dependant

One or more tender yellowish brown patches which develop slowly on the lower legs over several months. They may persist for years. They may be round, oval or an irregular shape. The centre of the patch becomes shiny, pale, thinned, with prominent blood vessels . A minor injury to an established patch can cause it to ulcerate. This is often painless

32The Skin in DMGranuloma Annulare

But there are variants- Generalised, Deep subcutaneous, Perforating etcThe localized variant usually needs no treatment and tends to clear byitself

One or more skin coloured bumps occur in rings in the skin over joints, particularly the knuckles. The centre of each ring is often a little depressed. Localised granuloma annulare usually affects the fingers or the backs of both hands, but is also common on top of the foot or ankle, and over one or both elbows.

Thought to be due to a delayed hypersensitivity reaction to some component of the dermis and the inflammation is mediated by tumour necrosis factor alpha (TNF).

33The Skin in DMDiabetic DermopathySeen in diabetics of at least 10 years plusIndicator of poor control in diabeticsHarmless, improves with glycemic control

Slightly sunken light brown or reddish, oval or round scars, on limbs especially on the shins

Exact cause of diabetic dermopathy is unknown but may be associated with diabetic neuropathic and vascular complications, as studies have shown the condition to occur more frequently in diabetic patients with microvascular disease

34The Skin in DMDiabetic bullosisblister-like lesions that occur spontaneously on the feet and hands of diabetic patientsIntraepidermal bullae these are blisters filled with a clear, sterile viscous fluid and normally heal spontaneously within 2-5 weeks without scarring and atrophy.Subepidermal bullae these are less common and may be filled with blood. Healed blisters may show scarring and atrophy.

Most cases diabetic bullae heal spontaneously without treatment

The Skin in DMDiabetic stiff skin

Thickening and induration.Especially dorsum of the fingers.Leads to clawing.Correlation with angiopathy.restricted mobility of the joints of their hands and stiff, waxy, thickened and yellowed skin.Finger pebbles = multiple, tiny, flesh-coloured papules on the dorsum of the fingers, knuckle pads and periungual areas.

The Skin in DMVitiligoidiopathic disorder of melanogenesis characterized by depigmented macules in an otherwise normal skin.Autoimmune spectrum and association

The Skin in DMNeuropathic ulcermechanical changes in conformation of the bony architecture of the foot, peripheral neuropathy, and atherosclerotic peripheral arterial diseasediabetic foot ulcers may be rated between 0 and 30: at risk foot with no ulceration1: superficial ulceration with no infection2: deep ulceration exposing tendons and joints3: extensive ulceration or abscessesManagement is needs off loading, surgery-debridement/vascular, dressing, antibiotics , grafting and glycemic control

The Skin in SarcoidosisErythema nodosumA form of panniculitisEarly stages, Red lumps appear on the shins or about the knees and ankle, hot and painfulColor change occurs over weeks--- Red to purpleRemember there are other causes!!

The Skin in SarcoidosisScar sarcoidosisGranulomatous lesions arising from scarsrare but highly specific for cutaneous sarcoidosisCan involve IM sites, tattoos,Cutaneous sarcoidosis is often not suspected, and clinical diagnosis is made on subsequent biopsySteroids topical or Oral

The Skin in SarcoidosisLupus perniolarge bluish-red and dusky purple infiltrated nodules and plaque-like lesions on nose, cheeks, ears, fingers and toesSarcoid specific and implies pulmonary and upper respiratory tract involvement due to disease

The Skin in SarcoidosisAnnular lesionsBrownish red and violaceous Vary in size and number

There are other variantsmacularpapular, verrucous, psoriaform etc