Skin signs of systemic disease

• The skin is a mirror of internal disease: patterns of rash, purpura, colour change, nail or mucosal change can point to a systemic diagnosis before any test result returns.
• Most skin signs are not specific to one disease. A sign becomes useful when it is read together with its distribution, morphology, associated symptoms and the system it implicates.
• Generalized pruritus without a rash is one of the commonest starting points: drugs, liver or kidney disease, haematological disease (especially iron deficiency), endocrine disease and occult cancer all have to be considered.
• Erythroderma (90% or more of the body surface red and scaling) is a dermatological emergency: stop the cause, support the skin barrier and admit early. ^[4]
• Palpable purpura on the lower legs in an adult is cutaneous small-vessel (leukocytoclastic) vasculitis until proven otherwise, and it demands a search for drugs, infection, connective tissue disease or malignancy.

By the end of this page you should be able to:

1. Recognise the common cutaneous patterns that point to systemic disease and sort them by urgency.
2. Take a history and perform an examination that uses distribution, lesion type and associated findings to narrow the differential.
3. Plan a work-up for generalized pruritus without an underlying dermatosis, including when imaging for cancer is justified.
4. Recognise erythroderma, name its main causes and outline its emergency management.
5. List the paraneoplastic skin signs and the malignancies they most often suggest.
6. Describe the characteristic skin signs of diabetes, thyroid, liver, kidney and connective tissue disease.
7. Distinguish palpable (vasculitic) from non-palpable purpura and outline the initial investigation of cutaneous small-vessel vasculitis.

This page is about using the skin as a clinical clue to disease in other organs. It is written for a student who can already describe rashes in morphological terms (macule, papule, plaque, purpura, vesicle, scale) and who now needs the link to what is happening inside. Where a skin finding is the hallmark of a single condition (for example the heliotrope rash of dermatomyositis, or pretibial myxedema of Graves disease) it is named here; where it is only a clue among many, the page says so. Every condition mentioned should be followed up in its own topic; this page supplies the map, not the deep pharmacology.

The approach is always the same. First decide whether the skin is diseased (a primary dermatosis) or only reacting to something systemic. Primary dermatoses usually have a characteristic distribution and morphology; systemic disease often presents with subtle, atypical or widespread findings and with symptoms outside the skin. Second, decide urgency: erythroderma, necrotic or haemorrhagic rashes, and any rash with systemic toxicity need same-day action. Third, let distribution narrow the field: sun-exposed, acral, pressure-dependent, flexural and periorbital patterns each have their own police list.

Throughout this page, thresholds and laboratory cut-offs come from the sources named in the references. The editors and educators who wrote those sources did not always agree; where they differ the value is given as a range.

A patient rarely presents with a label. The table below is a first-pass sorting tool: look up the presenting skin pattern, note the system it most often implicates, and look at the urgency column. It is not a substitute for taking the history and looking at the whole patient.

The history does most of the work in this topic. Each question below is included because it changes the probability of a named cause.

1. Onset and course. Did the rash appear over hours, days or months? Drug rashes and infections declared themselves quickly; paraneoplastic signs often parallel the tumour; chronic signs (diabetic dermopathy, acanthosis) drift in over years.
2. Distribution and symmetry. Symmetrical, gravity-dependent purpura suggests vasculitis. Only the knuckles and eyelids suggest dermatomyositis. Only the shins suggest necrobiosis lipoidica or diabetic dermopathy. A unilateral dermatomal band is not systemic at all (it is herpes zoster).
3. Lesion type and colour. The International Forum for the Study of Itch classification splits chronic pruritus into pruritus on diseased skin (group I, a dermatosis is present), pruritus on non-diseased skin (group II, systemic, neurogenic or psychogenic disease) and chronic secondary lesions from scratching (group III). ^[3] The distinction determines whether the work-up stays in dermatology or moves into medicine.
4. Exposure and drugs. Take a full drug history including over-the-counter, herbal and illicit substances, and a timeline. Drug rashes often appear within one to three weeks of starting the agent; leukocytoclastic vasculitis appears about one to three weeks after drug initiation and often seven to ten days after an infection or drug exposure. ^{[5] [1]}
5. Systemic symptoms. Fever, night sweats, weight loss, arthralgia, myalgia, abdominal pain, haematuria, dyspnoea and neuropathy each point to a system; fatigue and pruritus are non-specific but still worth quantifying.
6. Comorbidity and risk factors. Diabetes control, thyroid symptoms, alcohol intake, renal disease, liver disease, hepatitis exposure, HIV risk, pregnancy, and family history of autoimmune or endocrine disease.
7. Contact, travel and household. Scabies, bed bugs and pediculosis all cause pruritus and are often missed; travel raises parasitic infection.
8. What relieves it. Pruritus relieved by emollients rarely has a serious cause; pruritus unrelieved by simple measures and worsening at night leans towards renal, cholestatic or psychogenic disease.
9. Occupation and hobbies. Solvents, adhesives, cleaners and new cosmetics cause irritant and allergic contact dermatitis, which can scale up to an erythroderma after a systemic sensitisation.

A complete dermatological examination, including finger webs, anogenital region, nails and scalp, is the standard first step when pruritus is unexplained. ^[3] Then step back and look for systemic clues.

• Colour. Jaundice suggests cholestasis or hepatocellular disease; pallor suggests anaemia; a grey-brown colour (melanin following hemosiderin) suggests haemochromatosis; a lemon-yellow tint can be carotenaemia (diabetes, hypothyroidism, hypercarotenaemia). ^[2]
• Temperature and moisture. Warm, moist skin points to thyrotoxicosis; cold, dry skin to hypothyroidism. ^[2]
• Nutrition and edema. Wasting and oedema of the legs occur with nephrotic syndrome, cirrhosis and malignancy.
• Distribution of the lesion. Gravity-dependent purpura (lower legs, buttocks) is the hallmark of small-vessel vasculitis. ^[5]

Nail changes are cheap and informative. Half-and-half (Lindsay) nails occur in about 40% of patients on haemodialysis; Muehrcke lines (double white transverse bands) signal hypoalbuminaemia of less than 2.2 g per dL in nephrotic syndrome; Terry nails (white bed with a narrow distal band) are classically associated with cirrhosis. ^[2] Splinter haemorrhages raise vasculitis, infective endocarditis or trauma. Periungual telangiectasia, cuticular hypertrophy and dystrophy point to dermatomyositis. ^[1] Koilonychia suggests iron deficiency. Hyperpigmented longitudinal bands suggest Addison disease. ^[2]

Hair loss and texture matter too: diffuse thinning of the scalp and loss of the lateral third of the eyebrows occur in hypothyroidism; diffuse (telogen) alopecia in systemic lupus and iron deficiency; flagellate erythema or a pseudo-alopecia in dermatomyositis. ^{[1] [2]} Mucosal lesions (aphthae, telangiectasia, candidiasis, Kaposi sarcoma) can be the only sign in half of cases of systemic disease with mucosal involvement, so look in the mouth on every examination.

The skin signs of diabetes are numerous and split naturally into three groups: markers of insulin resistance, specific dermatoses, and complications of complications. ^[2] Acanthosis nigricans (velvety, hyperpigmented plaques in the axillae, neck and groins) is usually a sign of hyperinsulinaemia and often appears before glycaemic values become abnormal. ^[2] In a patient who is not obese and has no endocrine cause for acanthosis, sudden onset should raise suspicion of an underlying gastrointestinal adenocarcinoma, because more than 95% of paraneoplastic cases of acanthosis are adenocarcinomas. ^[2]

Necrobiosis lipoidica produces chronic, painless, yellow-brown, atrophic plaques with telangiectasia, usually on the shins, more common in women; about one in three ulcers. ^[2] Scleredema of Buschke gives woody induration of the neck, shoulders and back. Bullosis diabeticorum (tense, painless blisters on the lower limbs) occurs in roughly 0.5% of people with diabetes. ^[2] Diabetic dermopathy ("shin spots") is very common in older men with diabetes and tracks with microvascular complications such as nephropathy, retinopathy and neuropathy. ^[2] Granuloma annulare (annular papules on the dorsum of the hands and feet) is more common in people with diabetes but also in hepatitis, HIV and lymphoma. ^[2] Acquired perforating dermatosis (pruritic, umbilicated papules with a central keratotic plug) occurs in diabetes and in end-stage kidney disease. ^[2] Vitiligo and lichen planus (affecting about a quarter of people with lichen planus) cluster with diabetes through shared autoimmunity. ^[2] Recurrent or severe skin infections (cellulitis, candidiasis, dermatophytosis, malignant external otitis, mucormycosis in ketoacidosis) are often the first manifestation of undiagnosed diabetes. ^[2]

Hyperthyroid skin is warm, moist and smooth, with facial flushing, palmar erythema, hyperhidrosis, diffuse scalp thinning, onycholysis, generalised pruritus and chronic urticaria. Pretibial (or localised) myxedema (infiltrated, indurated plaques on the shins) and thyroid acropathy (soft-tissue swelling and clubbing of the fingers) are more specific to Graves disease. ^[2] Jellinek sign (hyperpigmentation of the eyelids) is also described. ^[1] Hypothyroid skin is dry, cold and blotchy, with carotenaemia, macroglossia, loss of the lateral third of the eyebrows, rough brittle hair, and non-pitting (myxedematous) thickening of skin. ^[2] Vitiligo, alopecia areata and dermatitis herpetiformis cluster with autoimmune hypothyroidism. ^[2]

Cirrhosis produces a long list that is worth knowing by heart because the findings are easy to miss: palmar erythema, spider naevi, flushing or a plethoric facies, caput medusae, pruritus, Terry or Muehrcke nails, thinning of body hair, xanthelasma, jaundice and a low threshold for bleeding. ^[2] Pruritus in chronic cholestatic disease is typically worse at night and in warmth, starts on the palms and soles, and may respond to cholestyramine, ursodeoxycholic acid or naltrexone. ^{[2] [3]}

Viral hepatitis has its own dermatological signature. Acute hepatitis B can present with periorbital oedema, a rash, lichenoid eruptions, serum sickness-like disease or polyarteritis nodosa. ^[2] Chronic hepatitis B and C produce urticarial vasculitis, lichen planus, mixed cryoglobulinaemia, Gianotti-Crosti syndrome, porphyria cutanea tarda, livedo reticularis and cryoglobulinaemic purpura. ^[2] Porphyria cutanea tarda presents with photosensitivity, tense bullae that heal with milia and scarring, and facial hypertrichosis; it is associated with hepatitis C, iron overload and (in haemodialysis patients) with uroporphyrin accumulation. ^[2] Wilson disease may produce a "blue lunula", Kayser-Fleischer rings and hyperpigmentation of the lower limbs. ^[2]

Uraemic pruritus is one of the most intense and disruptive symptoms in medicine: it affects roughly half to 90% of patients on haemodialysis, worsens at night, and may lead to nodular prurigo or acquired perforating dermatosis. ^[2] The characteristic distribution is the "butterfly sign" (the central back is spared). ^[2] Other uraemic skin signs are xerosis (50% to 80% of haemodialysis patients), dyspigmentation (yellow-grey or brown colour from retained urochrome and hemosiderin), half-and-half nails (40%), Muehrcke lines, thin brittle hair and a mucosal (xerostomia, uremic breath) pattern. ^[2] Uraemic frost (crystalline urea on the skin) is now rare and appears at serum urea levels of roughly 250 to 300 mg per dL. ^[2]

Nephrogenic systemic fibrosis follows gadolinium exposure in renal failure and produces thickened, bound-down plaques with "peau d'orange" skin. ^[2] Calciphylaxis occurs in 1% to 4% of haemodialysis patients with secondary hyperparathyroidism and a raised calcium-phosphate product (above roughly 60 to 70 mg squared per dL squared): extremely painful, symmetric, retiform purpuric plaques that ulcerate and necrose, usually over adipose areas (abdomen, thighs, buttocks), with very high morbidity. ^[2] Oxalosis (intravascular crystal deposits) resembles calciphylaxis but is more superficial and less painful. ^[2] Porphyria cutanea tarda and pseudoporphyria (no rise in porphyrins; triggered by furosemide, tetracyclines, isotretinoin, naproxen and UV light) are seen in 1% to 18% of dialysis patients. ^[2]

The connective tissue diseases need a section of their own because their skin signs are protean and, in lupus and dermatomyositis, have been written into diagnostic criteria.

Systemic lupus erythematosus. The LE-specific lesions are acute (malar rash, photosensitive, sparing the nasolabial fold; generalized ACLE), subacute (annular or papulosquamous plaques on sun-exposed skin that leave no scar) and chronic discoid (scarring plaques, often on the ears and scalp, with follicular plugging). ^[1] The 2019 EULAR/ACR criteria give points for each mucocutaneous item (non-scarring alopecia 2, oral ulcers 2, subacute or discoid lupus 4, acute lupus 6) and require 10 points overall, with a positive ANA as the necessary first criterion. ^[1] Non-specific LE lesions are many: leukocytoclastic vasculitis is the commonest (20% to 40%), urticarial vasculitis (lasting more than 24 hours, with a burning rather than itching quality), livedo (especially with antiphospholipid syndrome), Raynaud phenomenon (10% to 44% of patients, more with anti-U1RNP), erythromelalgia, digital gangrene, bullous lupus, papulonodular mucinosis, calcinosis, "lupus hair" (frail short hairs along the frontal hairline) and alopecia (non-scarring in active disease, scarring after discoid disease). ^[1] Pruritus can precede lupus by as much as 10 years. ^{[2] [3]}

Dermatomyositis. Pathognomonic signs are the heliotrope (violaceous, often oedematous periorbital erythema) and Gottron papules (violaceous papules over the interphalangeal and metacarpophalangeal joints); Gottron sign is the same colour on elbows and knees. ^[1] Characteristic but not specific findings include the V-neck and shawl signs (photosensitive violaceous erythema of the neck, chest and shoulders), holster sign (violaceous patches on the lateral thighs), mechanic's hands (hyperkeratotic, fissured fingers), periungual telangiectasia, cuticular hypertrophy, small haemorrhagic infarcts, scalp lesions with non-scarring alopecia, inverse Gottron papules and flagellate erythema. Calcinosis is commoner in juvenile than adult disease (30% to 70% versus 10%). Cutaneous vasculitis occurs mainly in juvenile dermatomyositis. ^[1] Vesiculobullous or necrotic skin lesions, or cutaneous vasculitis, should trigger a search for malignancy, and anti-transcriptional intermediary factor 1 gamma antibody is strongly associated with cancer in elderly patients. ^{[1] [2]}

Systemic sclerosis. Skin thickening is the defining sign. Limited disease affects the fingers, face (microstomy), neck and distal extremities with Raynaud phenomenon, telangiectasia and a tendency to pulmonary hypertension; diffuse disease involves proximal limbs and trunk with early cardiac, pulmonary, renal and gastrointestinal involvement and a high risk of scleroderma renal crisis. ^[1] Non-specific findings include cutis verticis gyrata, calcinosis, dyschromia with a "salt-and-pepper" pattern that spares the perifollicular skin, nailfold capillary changes (83% to 98% of cases) and digital ischaemia. ^[1] The diagnosis is supported by the 2013 ACR/EULAR criteria. ^[1]

Rheumatoid arthritis. Rheumatoid nodules occur in 20% to 30% of patients, usually in seropositive, erosive disease; they sit on extensor surfaces, can ulcerate and are cosmetically troublesome. Accelerated nodulosis (sudden growth of nodules over the hand joints, sometimes after methotrexate) and rheumatoid nodulosis are variants. ^[1] Palpable purpura and retiform purpura from rheumatoid vasculitis occur in 2% to 5% of long-standing seropositive patients and carry a high mortality. Bywater lesions (haemorrhagic infarcts of the nail folds) and palmar erythema are also seen. ^[1]

Sjogren syndrome. Sicca (dry eyes, dry mouth, dry skin with xerosis and pruritus) and Raynaud phenomenon (30%) are the commonest signs; cutaneous small-vessel leukocytoclastic vasculitis occurs in 10% (often before sicca symptoms) and when cryoglobulinaemic carries a poor prognosis and association with lymphoma. Anti-Ro (SSA)-positive patients may develop annular, polycyclic (subacute lupus-like) lesions in 9% of cases. ^[1] Pruritus and annular eruptions may precede the disease by years. ^[2]

Raynaud phenomenon is a useful bridge diagnosis: the triphasic colour change on cold exposure is primary (mild, fingertip) or secondary to connective tissue disease, vasculitis, paraproteinaemia, drugs or hypothyroidism. ^[1]

A skin sign is paraneoplastic when it is not a metastasis and not a side effect of treatment, but a remote effect of the tumour. Curth's postulates (simultaneous onset, parallel course, association with the same tumour type, statistical association, genetic association) are the classic framework used to judge whether the link is real, and they remind us that most "associations" in dermatology literature are not proven causal. ^[2] The following are the signs and the malignancies they most often flag. Percentages quoted are from the same review. ^[2]

The inherited syndromes (Cowden, Gardner, Muir-Torre, Peutz-Jeghers, Birt-Hogg-Dube, MEN, von Recklinghausen, tuberous sclerosis, hereditary leiomyomatosis and renal cell cancer) are the other route by which skin announces an internal cancer, and their cutaneous signs usually appear years before the tumour. ^[2]

Generalized pruritus as a paraneoplastic symptom deserves special mention: pruritus may precede or accompany the tumour, and the tumour group most often implicated is solid malignancy and lymphoproliferative disease. ^{[2] [3]}

Cutaneous vasculitis is the most common vasculitis encountered in practice. ^[5] It is not a single disease but an inflammation of small blood vessels that, under the microscope, shows a neutrophilic infiltrate, nuclear dust (leukocytoclasia), fibrinoid necrosis of the vessel wall and extravasation of red cells into the surrounding tissue. ^[5] The preferred sites are the lower legs and buttocks because of turbulence and hydrostatic pressure in the postcapillary venules. ^[5]

Clinical spectrum. The classic lesion is the palpable purpuric papule, a tiny, tender, non-blanching spot on the lower legs that appears in crops over hours and fades over two to three weeks leaving post-inflammatory pigmentation. ^[5] Lesions may merge into confluent purpura; urticarial wheals that persist longer than 24 hours and burn rather than itch; bullous-haemorrhagic purpura; or deep nodules and ulcers (when medium-sized vessels are involved). ^[5] Patients may be well or have fever, arthralgia, abdominal pain, haematuria, dyspnoea or neurological findings that dictate the urgency of the work-up. ^[5]

Why purpura is palpable. Palpable purpura is inflammation of the superficial vessel wall (leukocytoclastic vasculitis); non-palpable purpura is the result of non-inflammatory fragility (scurvy, Ehlers-Danlos syndrome, steroid or solar purpura, amyloidosis) or of platelet and coagulation defects. ^[5] This is the first decision point at the bedside. Sneaky mimics include infectious emboli (meningococcaemia, gonococcaemia, endocarditis), DIC, TTP, paraproteinaemia and cholesterol emboli, all of which can present as purpura. ^[5]

A useful grouping divides leukocytoclastic vasculitis by the 2012 revised Chapel Hill nomenclature: ANCA-associated (granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis), immune complex (cryoglobulinemic, IgA/Henoch-Schonlein, hypocomplementaemic urticarial, IgM/IgG immune complex), vasculitis associated with systemic disease (rheumatoid arthritis, lupus, Sjogren, sarcoidosis) and vasculitis with probable cause (drugs, infection, sepsis, neoplasms). ^[5] About half of cases have an identifiable underlying cause or systemic involvement; the other half is single-organ cutaneous small-vessel vasculitis (usually drug- or infection-related) or idiopathic. ^[5]

Causes and frequency. Cutaneous leukocytoclastic vasculitis is usually idiopathic or drug-induced. Infections are common triggers (group A streptococcal infection, hepatitis B and C, HIV, parvovirus, mycobacteria, staphylococci), with the rash appearing roughly seven to ten days after exposure. Drugs implicated include beta-lactams, sulfonamides, vancomycin, NSAIDs, allopurinol, furosemide, phenytoin, metformin, amiodarone, beta-blockers, TNF inhibitors and immune-checkpoint inhibitors, typically one to three weeks after starting the agent. ^{[2] [5]} Chronic hepatitis C is the main cause of cryoglobulinemic vasculitis (80% to 85% of cases). ^[5] Connective tissue diseases are the next large group. Underlying neoplasia, usually haematological, occurs more often in older patients with constitutional symptoms. ^[5] Cutaneous small-vessel vasculitis is also the skin component of ANCA-associated and other systemic vasculitides, and the same histological pattern can be found in them. ^[5]

Henoch-Schonlein (IgA) vasculitis deserves a separate note because it is the commonest childhood form (10 to 20 children per 100,000 per year, more than 90% under 10 years) and presents with the tetrad of palpable purpura, joint pain, abdominal pain or bleeding and renal involvement. ^[5] The biopsy shows IgA-dominant deposits by direct immunofluorescence. ^[5] In adults the skin-limited IgA-negative form is more common. Hypocomplementaemic urticarial vasculitis (anti-C1q vasculitis) presents with urticarial lesions lasting longer than 24 hours plus low complement and can associate with lupus, Sjogren syndrome and monoclonal gammopathy. ^[5] Waldenstrom hypergammaglobulinaemic purpura and cryoglobulinemic vasculitis are rarer but well described in the connective tissue disease group. ^{[1] [5]}

The BAD guidelines for generalized pruritus in adults without an underlying dermatosis (2018) and the AAFP review (2022), which incorporates them, set the standard approach; the European S2k guideline on chronic pruritus (2019) is a second useful reference. ^[3] The first step is always to separate diseased skin from non-diseased skin, and to look for a drug cause. Drugs are a common cause of pruritus (morphine and opioids, statins, ACE inhibitors, NSAIDs, digoxin, antimalarials and sulphonamides among the commoner ones) and the only way to test is to stop the suspected agent for a few weeks and observe. ^{[2] [3]}

If no primary skin disease is found, the baseline battery recommended by the guidelines and the review articles is: ^{[2] [3]}

If the screen is negative but suspicion remains, the extended list is: serum protein electrophoresis and urine protein electrophoresis, hepatitis serology, heavy-metal levels, parathyroid hormone, bone chemistry, serum vitamin B12 and D, stool for ova and parasites, and malignancy screening. ^{[2] [3]} A pruritus that is severe and persistent within the first three months, with no trigger or abnormal basic tests, is one of the few situations in which cross-sectional imaging of the neck, chest, abdomen and pelvis is justified, because this is the window in which occult malignancy most often declares itself. ^[2] Patients with significantly elevated LDH at presentation (above about 1.5 times the upper limit of normal) also warrant imaging. ^[2] If all investigations are negative but clinical suspicion persists, the basic screen can be repeated every three to six months. ^[2] (The AAFP review is the clearest accessible single source for the stepwise approach, and it cites the BAD 2018 guidelines by name.) ^[3]

Erythroderma is clinically defined as diffuse erythema involving 90% or more of the body surface, with variable scaling. ^[4] It is a reaction pattern, not a diagnosis, and patients almost always look unwell. Reported incidence is around one case per 100,000 adults per year, with the mean age of onset between 42 and 61 years and a higher incidence in men. ^[4] Roughly one third of cases follow a flare of a pre-existing dermatosis (psoriasis in about 23%, atopic dermatitis, contact or seborrhoeic dermatitis), about 20% are drug reactions, about 14% are lymphoma or leukaemia including Sezary syndrome, and about 30% remain idiopathic even after full investigation. ^[4] Congenital ichthyoses, infections and autoimmune disease make up most of the rest. ^[4]

Causes can be recalled with the mnemonic IDSCALP: idiopathic, infection, drug, seborrhoeic dermatitis, sarcoidosis, contact dermatitis, connective tissue disease, atopic dermatitis, autoimmune blistering disease, lymphoma and leukaemia, and psoriasis with pityriasis rubra pilaris. ^[4]

Typical features are coalescing erythematous patches with islands of sparing, scaling two to six days after the erythema, pruritus (worst in atopic dermatitis and Sezary syndrome), ridged and thickened nails, hair shedding, lymphadenopathy and systemic compromise from fluid and protein loss: hypoalbuminaemia, peripheral oedema, chills, fever and, at the extreme, high-output cardiac failure. Protein loss can exceed 9 g per square metre of body surface per day. ^[4]

Work-up: a full drug and skin history, an examination for lymph nodes, liver and spleen, baseline bloods (FBC with film, ESR, CRP, renal and liver function, albumin, IgE where relevant, HIV and hepatitis serology), a skin biopsy (often non-specific, and often repeated before the diagnosis declares itself), and imaging directed at occult malignancy when the cause is not obvious (chest radiograph, CT chest/abdomen/pelvis if lymphadenopathy or systemic symptoms are present). ^{[2] [4]} When the presentation resembles drug hypersensitivity with eosinophilia, DRESS must be considered. ^[4]

Management is emergency supportive care while hunting for the cause: admit, stop unnecessary drugs, regulate temperature (patients lose heat despite feeling hot), maintain hydration and electrolytes, replace protein, treat secondary infection, give bland emollients, wet dressings and mid-potency topical steroids on a quarter of the body at a time, and oral antihistamines for itching. Systemic corticosteroids should be avoided in erythrodermic psoriasis and in staphylococcal scalded skin syndrome. ^[4] Psoriasis is often treated with methotrexate, retinoids, ciclosporin or biologics; cutaneous T-cell lymphoma with topical or systemic agents per stage; pityriasis rubra pilaris with systemic retinoids. Idiopathic cases use emollients, topical or oral steroids, methotrexate, azathioprine or photochemotherapy. ^{[4] [2]} Idiopathic erythroderma should be re-biopsied over six to twelve months because cutaneous T-cell lymphoma can unmask itself with time. ^[2]

The supporting notes in the LCV review by Fraticelli and colleagues give the standard work-up. ^[5] Skin-limited disease needs only a basic screen (full blood count, chemistry, urinalysis) when a drug or infection is the obvious trigger and there are no systemic signs. ^[5] Otherwise arrange: full blood count and film; renal and liver function; urinalysis (haematuria, proteinuria); inflammatory markers; ANA and anti-extractable nuclear antigen panel; rheumatoid factor and anti-CCP; complement C3 and C4; ANCA; immunoglobulins and serum protein electrophoresis; cryoglobulins; hepatitis B, C and HIV serology; and ASO titres if streptococcal infection is suspected. ^[5] Arrange these before starting steroids where possible.

A punch biopsy, including the deep dermis, ideally taken from a lesion less than 48 hours old and before steroid therapy, confirms the diagnosis (direct immunofluorescence detects IgA, IgM, IgG and complement, with IgA-dominant deposition diagnostic of Henoch-Schonlein/IgA vasculitis). ^[5] Wedge biopsy is needed if medium-vessel disease is suspected. Imaging (chest radiograph; CT of chest, abdomen and pelvis) follows any clue to organ involvement. ^[5] Management of skin-limited disease is rest, elevation, compression, antihistamines and analgesia; if severe, a tapering course of oral corticosteroids (initially 0.5 to 1.0 mg per kg per day, tapered slowly to prevent rebound) can be used; chronic or recurrent cases add colchicine (0.5 to 1 mg per day), dapsone (50 to 200 mg per day, checking G6PD status first), hydroxychloroquine or immunosuppressants (azathioprine 1 to 2 mg per kg per day, methotrexate 0.2 to 0.3 mg per kg per week with folic acid, mycophenolate mofetil 2 to 3 g per day). Cryoglobulinemic vasculitis and IgA vasculitis with renal involvement are managed with higher immunosuppression and, in selected cases, rituximab or plasma exchange, in conjunction with the relevant specialist service. ^[5]

Where the presentation points to lupus, dermatomyositis or systemic sclerosis, the skin is only the starting point. The accompanying panel is the standard autoimmune work-up (full blood count, renal and liver function, urinalysis, ANA with ENA panel, complement, urine protein/creatine ratio, creatine kinase, ESR/CRP, and imaging as clinically indicated), and it sits outside the scope of this skin-focused page but should be started the same day. ^[1]

Chronic pruritus is defined as six weeks or longer in duration (an acute episode is under six weeks). ^[3]

• Pruritus. Treat the cause once found. Symptomatic measures are consensus-based European recommendations: avoid triggers, limit bathing to 20 minutes in lukewarm water, use mild perfume-free soap, apply emollients (especially after bathing), keep the bedroom cool, and use oral antihistamines and topical corticosteroids or calcineurin inhibitors for inflammatory skin disease. Gabapentin, pregabalin, SSRIs, montelukast, capsaicin and phototherapy (narrowband UVB, UVA-1) are the system-specific options listed in the AAFP review. ^[3]
• Erythroderma. Admit when the patient is haemodynamically compromised; otherwise urgent dermatology assessment. Stop unnecessary drugs, monitor temperature, fluids and electrolytes, replace protein, treat infection, give bland emollients and mid-potency topical steroids on limited areas, antihistamines and targeted therapy by cause.
• Purpura/vasculitis. Stop the offending drug if identified; rest, elevation and compression; treat infection. Give systemic steroids only when skin disease is severe or recurrent, and immunosuppression when systemic vasculitis is present. ^[5]
• Paraneoplastic signs. Investigate promptly: weight loss or constitutional symptoms accompanying a skin sign should trigger age-appropriate and symptom-directed cancer screening rather than observation. ^[2]
• Organ-specific signs. Diabetes, thyroid, liver and kidney signs are managed by treating the underlying disease; the skin finding resolves, persists or only partly improves, and that behaviour is itself a clinical clue.

Refer same day for any erythroderma, retiform purpura or necrosis, bullous detachment, any purpuric rash with systemic toxicity, and any acanthosis or paraneoplastic sign with weight loss. Refer urgently for suspected connective tissue disease with systemic features (renal, pulmonary, cardiac, muscle weakness, dysphagia), for suspected vasculitis with organ involvement (haematuria, abdominal pain, haemoptysis, neuropathy), and for persistent, unexplained pruritus with constitutional symptoms. Routine referral is appropriate for pruritus or skin signs needing an autoimmune panel, dermatology biopsy or phototherapy, or when cosmetic (diabetic dermopathy, acanthosis) or chronic (erythroderma unresponsive to first-line therapy) problems dominate.

A careful history and a full skin and mucosal examination, including nails and hair, cost nothing and give most of the diagnosis in this topic. Baseline bloods (FBC, ferritin, renal and liver function, glucose, TSH, ESR) and a skin punch biopsy (or a careful examination where pathology is unavailable) carry most of the work-up. Erythroderma can be managed safely in a general ward: stop offending drugs, keep the patient warm, support hydration and nutrition, prevent sepsis and use bland emollients; topical steroids on limited areas are more useful than systemic steroids when infection cannot be excluded. In calciphylaxis and severe vasculitis, where infusion and immunosuppression are unavailable, early referral to a centre that has them saves lives.

• The skin is often the first detectable sign of internal disease; learn the handful of high-yield patterns (erythroderma, palpable purpura, heliotrope, pretibial myxedema, acanthosis, necrobiosis lipoidica, Terry nails, uraemic frost).
• Most signs are not disease-specific. Read the morphology together with distribution, lesion chronology and the patient's systemic symptoms.
• Primary skin disease and systemic disease are separated first by deciding whether the skin itself is diseased (pruritus on diseased skin versus non-diseased skin; primary dermatosis versus reactive change).
• Erythroderma is a reaction pattern, not a diagnosis: 90% or more of body surface area red and scaling; psoriasis, atopy, contact dermatitis, drugs, cutaneous T-cell lymphoma and idiopathic causes dominate; admit when systemically unwell; stop systemic steroids in psoriatic or drug-related cases where appropriate and avoid them in scalded skin syndrome. ^[4]
• Generalized pruritus without a rash usually needs a structured screen: FBC and iron studies, renal and liver function, glucose or HbA1c, TSH, inflammatory markers, urinalysis, and chest radiograph, with HIV/hepatitis serology and imaging as indicated.
• Iron deficiency is the commonest systemic cause of generalised pruritus; ferritin is an acute-phase protein and can be normal despite deficiency.
• Drugs commonly cause pruritus (opioids, statins, ACE inhibitors, NSAIDs, digoxin, antimalarials, sulphonamides) and the diagnosis is made by stopping the agent.
• Severe or persistent pruritus within the first three months with no cause is the classic indication for imaging of the neck, chest, abdomen and pelvis.
• Palpable purpura on dependent surfaces is cutaneous small-vessel (leukocytoclastic) vasculitis; non-palpable purpura has different causes; direct immunofluorescence of a fresh (less than 48-hour) biopsy clinches the type.
• Vasculitis in adults usually has an underlying systemic cause; IgA vasculitis dominates in children and carries a risk of renal disease.
• Connective tissue skin signs have entered modern diagnostic criteria (lupus EULAR/ACR 2019; systemic sclerosis ACR/EULAR 2013; ANCA and Chapel Hill 2012 for vasculitis) and give a reproducible way of describing a rash.
• Paraneoplastic signs (acanthosis, Leser-Trelat, Bazex, tripe palms, hypertrichosis lanuginosa, erythema gyratum repens, dermatomyositis in adults) should be followed by prompt, proportionate cancer screening, not reassurance.

Connective tissue diseases (lupus, dermatomyositis, systemic sclerosis, Sjogren syndrome, rheumatoid arthritis); diabetes mellitus (chronic complications); thyroid disease (hyperthyroidism, hypothyroidism, gravity-dependent oedema?); liver cirrhosis and viral hepatitis; chronic kidney disease and dialysis; vasculitis (ANCA-associated vasculitis, cryoglobulinaemia, Henoch-Schonlein/IgA vasculitis, hypocomplementaemic urticarial vasculitis); paraneoplastic syndromes; erythroderma; generalized pruritus; nutritional deficiency (iron); coagulation and purpura.