4) Multifocal Eosinophilic Granuloma Flashcards
Types of MEG
- Porphyria
- Ascorbic acid deficiency
- Zinc deficiency
- Niacin deficiency
- Hypercorticism
- Adrenal cortical insufficiency
- Hyper/hypothyroidism
- Xanthomas
- Neurofibromas
- Tuberculosis sclerosis
- Venous insufficiency and related
- DM & related
DM & related MEG types
- Diabetic dermopathy
- Necrobiosis lipoidica diabeticorum
- Diabetic bullae
- Acanthosis nigricans
Porphyria
- 1:25,000 in US, 1:1 female to male, generally adults
- Deficiency or mutation in uroporphyrinogen decarboxylase (UROD)
- Hereditary 20% vs Sporadic 80%
- Blistering photosensitivity
- Elevated plasma and urine total porphyrins
Porphyria cutanea tarda (PCT)
- Most common type of cutaneous porphyria while hepatoerythropoietic porphyria (HEP) is very rare with only 40 documented cases
- Iron-related and generally presents in adulthood while
HEP can present in children or adults depending on the degree of UROD deficiency
PCT classifications
- Inherited or sporadic
- Approximately 20 and 80 percent of cases, respectively
- Based on the presence or absence of heterozygous UROD mutations
PCT leads to
- Excess of porphyrins which are transported from the liver to the skin
- Leads to cutaneous phototoxicity
Acquired susceptibility factors for porphyria
- Alcohol use
- Smoking
- Estrogen use
- Hepatitis C virus or HIV infection are common
- Hemochromatosis mutations
Typical features of porphyria
- Chronic blistering photosensitivity commonly on the backs of the hands and other sun-exposed areas
- Can lead to infection, bullae, increased skin fragility, scarring, hyper- and hypopigmentation
Porphyria lesions
- May be pruritic and/or painful depending on stage and degree of severity
- Delayed cutaneous reaction to sun exposure which may result in the patient not being aware that the exposure is causing
the skin lesions
Porphyria diagnosis
- First line testing with measurement of plasma or urinary total porphyrins before more extensive testing
- Biopsy is not necessary unless trying to rule out another condition
- Once Dx is made, it is appropriate to have family members tested for UROD and/or hereditary hemochromatosis
Porphyria DDx
- Other cutaneous porphyrias which may or may not blister
- Epidermolysis bullosa
- Pseudoporphyria
- Phototoxic drug reactions and eruptions
Porphyria treatment
- Phlebotomy or low-dose hydroxychloroquine
- Reduction of susceptibility factors
- Choice between phlebotomy and hydroxychloroquine depends on the degree of iron overload and other susceptibility factors
Ascorbic acid deficiency
- Vitamin C deficiency known as “Scurvy”
- Essential dietary nutrient in humans
Ascorbic acid deficiency characteristics
- Ecchymosis and bleeding gums, perifollicular hemorrhage, petechiae and coiled hairs
- Symptoms are due to impaired collagen synthesis and disordered connective tissue secondary to deficiency
Ascorbic acid deficiency occurence
- Mostly in severely malnourished individuals, drug and alcohol abusers, or those living in poverty or on diets devoid of fruits and vegetables
Ascorbic acid deficiency symptoms
- Generally occur when the plasma concentration of ascorbic acid is less than 0.2 mg/dL
- Most specific symptoms, as early as three months, are follicular hyperkeratosis and perifollicular hemorrhage, with petechiae and coiled hairs
Common symptoms associated with ascorbic acid deficiency
- Ecchymosis
- Gingivitis (with bleeding and receding gums and dental caries)
- Sjogren’s syndrome
- Arthralgias, edema, anemia, and impaired wound healing
Hemorrhagic skin lesions associated with ascorbic acid deficiency
- Initially flat but may coalesce and become palpable
- Especially on the lower extremities which may resemble a systemic vasculitis
Musculoskeletal pain associated with ascorbic acid deficiency
- May be severe
- Can be caused by hemorrhage into the muscles of periosteum
Generalized systemic responses of ascorbic acid deficiency
- Weakness
- Malaise
- Joint swelling, arthralgias
- Anorexia
- Depression
- Neuropathy
- Vasomotor instability
Ascorbic acid deficiency imaging
- Sclerotic and lucent metaphyseal bands with periosteal reaction
- Adjacent soft-tissue edema
Ascorbic acid deficiency diagnosis
- Clinically and usually related to a direct history of vitamin C deficiency
Ascorbic acid deficiency treatment
- Vitamin C supplementation and reversal of the conditions that led to the deficiency
- Adults are usually treated with 300 to 1000 mg daily for one month
- Children recommended doses are 100 mg ascorbic acid given three times daily for one week, then once daily for several weeks until the patient is fully recovered
Ascorbic acid deficiency symptom resolution
- Many of the constitutional symptoms improve within 24 hours of treatment
- Bruising and gingival bleeding resolve within a few weeks
Zinc deficiency
- Mild deficiency is characterized by impaired growth velocity
- Severe depletion leads to growth retardation
- Dermatologic changes occur primarily in the extremities or around body orifices
Zinc biological role
- Forming tight bonds with certain amino acids
- Structural role in proteins
Zinc deficiency in chronic diseases
- Malnutrition (elderly, alcoholism, etc.)
- Malabsorption syndromes (gastric bypass, TPN, etc.)
- Diabetics due to alteration in zinc metabolism
Clinical manifestations of zinc deficiency
- Delayed sexual maturation, impotence, hypogonadism, oligospermia
- Alopecia
- Dysgeusia (impaired taste)
- Immune dysfunction
- Night blindness
- Impaired wound healing and various skin lesions
Zinc deficiency lesions
- Erythematous, vesiculobullous, and pustular lesions
Zinc deficiency treatment
- Supplementation is the mainstay of treatment
- Ranges from approximately 4 to 14 mg/day orally
- Good sources of zinc are in animal products such as meat, seafood, and milk while cereal contains the greatest amount of zinc for vegetarians/vegans
Acrodermatitis enteropathica (AE)
- Autosomal recessive disease in which zinc absorption is impaired
- Characterized by diarrhea, dermatitis, alopecia, poor growth, and poor immune function
Zinc deficiency dermatitis
- Consists of hyperpigmented skin lesions on the acral surfaces of the upper and the lower extremities, as well as the face and buttocks
Zinc deficiency onset
- Symptoms usually appear in early infancy, once breast-feeding is completely discontinued
Niacin deficiency
- Causes pellagra (raw skin)
- Commonly occurs in alcoholics
- Characterized by a photosensitive pigmented dermatitis
- Red tongue and many non-specific symptoms
Niacin deficiency characteristics
- Symmetric hyperpigmented rash, similar in color and distribution to a sunburn, which is present in the exposed areas of skin
- Red tongue, diarrhea and vomiting
- Neurologic symptoms including insomnia, anxiety, disorientation, delusions, dementia, and encephalopathy
Niacin deficiency may be seen in
- Carcinoid syndrome
- Prolonged isoniazid use
- Hartnup disease (due to effect on tryptophan)
Niacin deficiency supplementation
- 6 to 12 mg daily in children
- 16 mg for adult males
- 14 mg daily for non-pregnant adult females
Hypercortisolism characteristic findings
- Easy bruisability (loss of subcutaneous connective tissue)
- Purple striae (fragile skin stretches due to enlarging trunk)
- Skin atrophy (thinning stratum corneum, loss of subcutaneous fat)
- Cutaneous fungal infections (especially tinea versicolor)
Cushing syndrome
- Hypercortisolism
Hypercortisolism characteristic findings (continued)
- Hyperpigmentation
- Acanthosis nigrans
- Surgical or traumatic scars
Hyperpigmentation in hypercortisolism
- Induced by increased ACTH secretion
- Most noted in conspicuous areas such as face, neck, and hands or areas of friction or pressure such as waist, elbows, etc.
Acanthosis nigrans in hypercortisolism
- Present in the axillae and
around the neck (also seen in 40% of Type 2 DM)
Surgical or traumatic scars in hypercortisolism
- Form when plasma ACTH concentrations are markedly elevated are permanently pigmented
- In comparison, scars incurred before ACTH hypersecretion or after it is reduced are not pigmented
Adrenal insufficiency (Addison’s) hyperpigmentation
- Excess ACTH resulting in brown pigmentation
- Distribution similar to Cushing’s
- Noted in conspicuous areas such as face, neck, and hands or areas of friction or pressure (waist, elbows, etc.)
- Patchy pigmentation on inner surface of lips and buccal mucosa
- Scars are also hyperpigmented
Autoimmune primary adrenal insufficiency
- Patchy and often bilaterally symmetrical areas of depigmented skin (vitiligo) occur in 10-20% of patients about the trunk or extremities
Hypothyroidism clinical features
- The skin is cool and pale because (decreased blood flow)
- Epidermis has atrophied cellular layer and hyperkeratosis (dry roughness)
- Yellowish tinge (if carotenemia)
- Hyperpigmentation (primary hypothyroidism associated with primary adrenal failure)
- Hair may be coarse, hair loss is common
- Brittle nails
- Nonpitting edema (myxedema) occurs in severe hypothyroidism
Nonpitting edema (myxedema) in hypothyroidism
- Occurs in severe hypothyroidism and may be generalized
- Results from infiltration of the skin with glycosaminoglycans with associated water retention
Hypothyroidism clinical features (continued)
- Skin is warm (increased blood flow)
- Hyperpigmentation (ACTH secretion)
- Thinning hair, onycholysis, softening nails
- Vitiligo and alopecia
Grave’s Hyperthyroidism
- Pruritis and hives
- Infiltrative dermopathy most commonly overlying the shins
- Presents as raised, hyperpigmented, biolaceous orange peel textures papules
Diabetic dermopathy
- Approximately one-half of diabetic patients presents with multiple asymptomatic, round, dull red to pink papules or plaques predominantly located on the pretibial skin
Diabetic dermopathy lesions
- Evolve in one to two weeks to well-circumscribed, atrophic, brown macules and patches, often with fine scale
- Older lesions show epidermal atrophy and scattered hemosiderin deposits
Diabetic dermopathy Dx/Tx
- Dx is clinical and biopsy is not routinely done
- There is no treatment
- Lesions may resolve spontaneously over time or persist indefinitely
Necrobiosis Lipoidica Diabeticorum
- Rare, chronic granulomatous disease (commonly involving the lower legs, especially the shins)
- Lesions begin as red-brown or violaceous papules or nodules and progresses to yellow-brown, atrophic, telangiectatic plaques
- Ulceration often followed minor trauma
Necrobiosis Lipoidica Diabeticorum Dx/Tx
- Clinical and punch biopsy to confirm
- Tx for nonulcerated: corticosteroid followed by intranasal therapy in case of insufficient response
Diabetic bullae
- Bullous disease of diabetes is a term used to describe the abrupt development of noninflammatory, tense, subepidermal bullae in patients with diabetes in sites of otherwise normal-appearing skin
Diabetic bullae lesions
- Most commonly occur on the feet or lower legs
- May be up to several centimeters in diameter and are non painful
- Bullae spontaneously resolve over the course of a few weeks
Xanthomas
- Eruptive xanthomas are 1 to 5 mm erythematous to yellow papules
- Appear in crops and have an abrupt onset most commonly on extensor surfaces of the extremities and buttocks
Cutaneous xanthomas characteristic histology
- Lipid- laden macrophages, also known as “foam cells”
- Eruptive type has prominent extracellular lipid deposition
- Tuberous type have large foam cells with fibrosis
Tuberous xanthomas
- Solitary or grouped
- Can reach sizes up to 3 cm
- Yellow-orange or erythematous papules or nodules located over joints or extensor surfaces of the extremities (especially the elbows and knees)
Xanthomas Tx
- Pharmacologic treatment of dyslipidemia is usually indicated
- Often leads to concomitant improvement in eruptive and tuberous xanthomas caused by hyperlipidemia
Xanthoma resolution
- Eruptive: several weeks when triglyceride levels are reduced
- Tuberous and tendinous: slower to regress during treatment of dyslipidemia
Neurofibromatosis
- Type 1 with café-au-lait macules, freckling, Lisch nodules, and neurofibromas
- Discrete cutaneous neurofibromas most common
- Plexiform neurofibromas may be located superficially and associated with overgrowth of skin and soft tissues
- 70% with NF2 have cutaneous manifestations
The characteristic skin findings that contribute to establishing the diagnosis of neurofibromatosis
- Six or more cafe-au-lait macules of greatest diameter
>5 mm in prepubertal and >15 mm in postpubertal individuals - Two or more neurofibromas of any type or one plexiform neurofibroma
- Freckling in the axillary or inguinal regions
Tuberous sclerosis complex (TSC)
- An inherited neurocutaneous disorder
- Characteristic skin lesions are seen in 81-95% of patients
Tuberous sclerosis complex characteristics
- Hypopigmented macules (ash-leaf spots) usually elliptic in shape
- Angiofibromas (malar region of face)
- Ungual fibromas
- Shagreen patches (lower back)
- Distinctive brown fibrous plaque on the forehead
TSC brown fibrous plaque on forehead
- May be the first and most readily recognized feature
- Physical examination of affected neonates and infant
Venous insufficiency
- Chronic lower extremity venous disease
- Most common vascular disorder presenting with abnormal venous dilation (ie, telangiectasias, reticular veins, varicose veins), edema, inflammation, dermatitis, or ulceration
Venous insufficiency pigmentation changes
- Secondary to hemosiderin deposition
- Initially most prominent at the medial ankle
- May subsequently encroach upon the foot and lower leg
Venous insufficiency pruritis
- Dry, scaly skin that can be difficult to relieve
- Excoriations are often present secondary to scratching (can be source of infection)
Venous insufficiency severe cases
- Lipodermatosclerosis with brawny edema or even ulceration may develop
Venous insufficiency treatment
- Compression therapy along with symptomatic support
- Leg elevation, exercise, and pharmacological therapy
- Venous ablation and sclerotherapy
