Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb Cutaneous Manifestations of systemic diseases Dr. Eman Almukhadeb CUTANEOUS MANIFESTATIONS OF DIABETES MELLITUS:
Specific manifestations:
1 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
1. Diabetes dermopathy or “SHIN SPOTS”:
Most common cutaneous manifestation of diabetes; M > F, males over age 50 years with long standing diabetes.
They are: bilateral, symmetrical, atrophic red-brownish macules and patches, over the shins mainly but can occur at any sites, asymptomatic.
There is no effective treatment.
2. Necrobiosis Lipoidica Diabeticorum (NLD):
Patients classically present with single or multiple red-brown papules, which progress to sharply demarcated yellow-brown atrophic, telangiectatic erythematic plaques with a violaceous, irregular border. Usually it’s unilateral.
Common sites include shins followed by ankles, calves, thighs and feet.
Very atrophic plaque so any trauma will lead to ulceration, it occurs in about 35% of cases. Cutaneous anesthesia, hypohidrosis and partial alopecia can be found
Pathology: Palisading granulomas containing degenerating collagen. The nonenzymatic glycosylation of dermal collagen and elastin will lead to degeneration of the collagen and atrophy (necrobiosis).
2 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Approximately 60% of NLD patients have diabetes and 20% have glucose intolerance. Conversely, up to 3% of diabetics have NLD, so if a patient has NLD its common that he is diabetic, but not every diabetic patient have NLD. (Important)
Women are more affected than men.
Treatment: Ulcer prevention (by avoiding trauma). No impact of tight glucose control on likelihood of developing NLD.
There are multiple treatment options available and all of them reported to be effective: o Intralesional steroids o Systemic aspirin: 300mg/day and dipyridamole: 75 mg/day. o Antiplatelet. o Pentoxyfylline. o Preilesional heparin injection.
Hyperpigmentaion and thickening of the skin of the neck. It’s common to see it in any patient, not only in diabetic patients.
Causes: Its not only present with diabetes, it can occur in other conditions like: o Obesity. o Insulin resistance. o Endocrinopathy: DM, acromegaly, Cushing syndrome, hypothyroidism, Addison disease and hyperandrogenic state as; PCOS, HAIRAN syndrome (hyperandrogen, insulin resistance, acanthosis nigricans). o Malignancy (esp. GIT, Lung and Breast CA). o Medications (nicotinic acid, niacinamide, testosterone, OCP and Glucocorticoid).
Clinical picture: Hyperpigmented velvety plaques of the flexures; the neck, axial, antecubital fossa, popliteal fossa. Other sites include: The face, external genitalia, medial thighs, dorsal joints, lips and umbilicus can be involved in extensive cases.
Pathogenesis involves: o Genetic sensitivity of the skin to hyperinsulinemia. o Aberrant keratinocyte and fibroblast proliferation stimulated by excess growth factor (e.g., Insulin like growth factor).
3 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Treatment: Treat the cause: Tight blood glucose control, treatment of underlying malignancy, weight control, and discontinuation of offending agent.
4. Diabetic Bullae OR Bullosis Diabeticorum:
Non-inflammatory bullae. Rarest cutaneous complications of diabetes; M > F, long standing diabetics. Trauma and microangiopathy may play a role. Clinical picture: Rapid onset of painless tense blisters on the hands and feet. Pathology: Intraepidermal and/or subepidermal split without acantholysis. DIF is negative, because its not an inflammatory bullae. Treatment: Spontaneous healing in two to five weeks
5. Grannloma Annulare: Clinical picture: Asymptomatic red-purple dome shaped papules arranged in annular configuration. Association between granuloma annulare and diabetes is controversial. Usually when there is multiple granuloma annulare there is more risk of association with DM. Generalized form of GA is the most closely associated with DM, about 20%. It has a chronic and relapsing course. Treatment : . Intralesional steroid. . Systemic steroid. . PUVA and many other options. . Controlling blood sugar WILL NOT improve GA.
4 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
6. Scleredema Diabeticorum:
Occurs more commonly in type 2 diabetics, long-standing disease, and obese men (M>F).
Clinical picture: Painless, symmetric woody “peau d’orange” indurations and thickening of the upper back and neck (Interscapular area), and usually it affect the shoulder motility.
No specific treatment is available
7. Cutaneous Infections: Diabetic patients are predisposed to develop cutaneous infections due to poor microcirculation and low immunity: candidal Bacterial Fungal (Tinea pedis)
OTHER MANIFESTATIONS OF DIABETES MELLITUS: Pruritus (Itching). Yellow Skin or Carotenosis.
Eruptive Xanthomas: Diabetic neuropathy (peripheral), Neuropathic Xanthoma can occur in DM, it is a ulcers. lipid disposition in the skin. 5 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb CUTANEOUS MANIFESTATIONS OF THYROID DISEASE:
(Hyperhidrosis)
*
* Thyroid acropachy is a cutaneous condition characterized by digital clubbing and swelling of digits and toes.
NON-SPECIFIC MANIFESTATIONS OF HYPERTHYROIDISM: Skin: o Warm, and moist. o Localized or generalized hypertrichosis. o Palmar erythema. o Flushing of head/neck, trunk.
Hair: o Soft/fine/straight. o Diffuse reversible alopecia (Telogen effluvium).
Nails: o Faster rate of growth. o Onycholysis. o Plummer nails: concave deformity with distal onycholysis.
Pigmentation: o Focal or generalized hyperpigmentation.
6 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
o Vitiligo.
GRAVES Disease: Autoimmune Hyperthyroidism.
1. Thyroid Dermopathy (Pretibial Myxedema): Bilaterally symmetric, non-pitting yellowish-brown to red waxy papules, nodules and plaques on the shins Occur in Graves’s disease. The clinical findings are due to an increase in hyaluronic acid in dermis. Treatment regimens include high potency topical steroids & intralesional steroid. Remember that Pretibial Myxedema that occurs with GRAVES Disease (Autoimmune HYPERthyroidism) is different from the Myxedema that occurs with HYPOthyroidism.
2. Exophthalmoses.
3. Thyroid acrophachy.
NON-SPECIFIC MANIFESTATIONS OF HYPOTHYROIDISM: Skin: o Cool, dry, pale. o Xerosis (is an abnormal dryness of the skin or mucus membranes). o Hypohidrosis. o Yellowish hue secondary to carotenemia. o Generalized myxedema: swollen waxy appearance. o Swollen lips, broad nose, macroglossia. o Purpura secondary to impaired wound healing.
Hair: o Dry, brittle, coarse. o Increase in percentage of telogen hairs. o Diffuse alopecia. o Loss of lateral third of eyebrow (madarosis).
7 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
* Thickening of the palm and sole.
Ichthyosis: refers to a relatively uncommon group of skin disorders characterized by the presence of excessive amounts of dry surface scales.
CUTANEOUS MANIFESTATIONS OF ADDISON’S DISEASE (HYPOCORTICISM):
ADDISON’S DISEASE is a chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones.
Clinical picture: Generalized hyperpigmentation that is more prominent in light exposed areas, scars, genitalia, palmar and finger creases, and under the nails. The pigmentation characteristically affects the mucous membranes.
It is because of the increased amount of ACTH, which have an action similar to melanocyte-stimulating-hormones (MSH), so it will stimulate melanocytes that will cause pigmentations. (Important)
8 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Loss of pubic and axillary hair in females; androgen-dependent areas (because the androgens hormones are secreted from the adrenal gland).
Improvement of acne (The same mechanism as above).
Cushing syndrome: Endogenous or exogenous. Deposition of fat over the clavicles and back of the neck” Buffalo hump”. rounded erythematosus face with telangiectasia “Moon face” Trunkal obesity with slender wasting limbs. Striae distensae . Hirsutism, acneform rash, androgenetic alopecia. (Hyperandrogenism). Addisonian-like pigmentation. Easy bruising of the skin on simple trauma.
9 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Buffalo Hump. Striae Distensae.
Buffalo Hump. Striae Distensae.
, because steroids will cause immunosupression.
, monomorphic, no-comedons.
Acromegalcy:
Skin is oily (because of large sebaceous glands) and wet due to hyperhidrosis with wet hands on hand shaking. The lower lip is thickened, protruded with wide spaced teeth. Large and furrowed tongue. Increased skin pigmentation. Hirsutism. Acanthosis nigricans.
10 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb Hyperlipoproteinemia:
Type I o Familial lipoprotein lipase deficiency (AR) or apoprotein CII deficiency o Increased chylomicrons o Associated with hepatomegaly, pancreatitis Type IIa o Familial hypercholesterolemia, common hypercholesterolemia (AD) o Increased LDL
Type IIb o Familial hypercholesterolemia (AD) o Increased LDL and VLDL
Type III o Familial Dysbetalipoproteinemia (AR) o Increased IDL
Type IV o Familial hypertriglyceridemia (AD) o Increased VLDL
Type V o Familial type V hyperlipoproteinemia, familial lipoprotein lipase deficiency (AD) o Increased chylomicrons and VLDL
Xanthomatosis: 6 Clinical Types:
1. Tuberous Xanthoma: Flat or elevated, rounded, grouped, o yellowish-orange nodules over joints (particularly elbows and knees) o Types II, III, and IV. o Biliary cirrhosis.
Tuberous xanthomas of the knee. Note the yellowish hue. 2. Tendinous Xanthoma: Papules or nodules over tendons (extensor tendons on dorsum of hands, feet, o and achilles). o Types II, III.
Tendinous xanthomas of the fingers in a patient with homozygous familial hypercholesterolemia.
11 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Tendinous xanthoma: Linear swelling of the Achilles area representing a tendinous xanthoma in a patient with dysbetalipoproteinemia.
3. Eruptive Xanthoma: Very Important. Small multiple yellow/orange/red o papules appearing in crops over entire body → buttocks, flexor surfaces, arms, thighs, knees, oral mucosa and may koebnerize. Associated with markedly elevated o or abrupt increase in triglycerides (elevated chylomicrons) Types l ,lll , lV , and V o It can occur in patients who have o Diabetes, obesity, pancreatitis, chronic renal failure, hypothyroidism, estrogen therapy, corticosteroids, isotretinoin, o acitretin Eruptive xanthomas. Note the yellowish hue
4. Planar Xanthoma: Flat macules or slightly elevated o plaques, yellow/tan color Associated with biliary cirrhosis, biliary o atresia, myeloma, monoclonal gammopathy, lymphoma. Characteristically around eyelids, neck, o trunk, shoulders, or axillae o Types ll,lll
Plane xanthoma in a patient with a monoclonal IgG gammopathy
12 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
5. Palmar Xanthoma: o Nodules and irregular plaques on palms and flexural surfaces of fingers o Type III
Plane xanthomas of the palmar creases in a patient with dysbetalipoprotenemia (arrows).
6. Xanthelasma: o Most common type of xanthoma o Eyelids o Usually present without any other disease, but can occur in types II and III. o Common among women with hepatic or biliary disorders, also seen in myxedema, diabetes. o Best treated with surgical excision.
Xanthelasma palpebrarum with typical yellowish hue. Courtesy of Yale Residents Slide Collection.
13 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb CUTANEOUS MANIFESTATIONS OF Inflammatory Bowel Disease (IBD): o Cutaneous and oral ulcerations.
Association Cutaneous Findings Fissures and Fistulas CD > UC Commonly involves perineum associated with edema and inflammation Oral Crohn’s CD Edema, cobblestone, ulcerations, nodules Metastatic Crohn’s CD Nodules, plaques, ulcerations; commonly on extremities or intertrigenous regions mimics Erythema Nodosum. Erythema nodosum UC>CD Tender red nodules on anterior lower legs; precedes or occurs simultaneous with IBD flare
14 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Pyoderma Gangrenosum UC>CD Papules, pustules, hemorrhagic blisters (PG) → enlarge, ulcerate with dusky undermined edges; exacerbated by trauma; frequently on legs Pyoderma Vegetans UC Vegetating plaques, vesiculopustules of intertrigenous areas; heal with hyperpigmentation; when process involves mucosa =Pyostomatits vegetans Chronic Apthous Ulcers UC>CD Identical to common aphthous ulcers; develop with IBD flares
Metastatic Crohn’s disease:
The pathology in the skin is exactly the same as in the intestinal lesion.
It can present with ulceration or plaque or vesicle nodules. It can occur anywhere in the skin but mainly over androgynous area.
Erythema nodosum: Inflammation of SC fat. Clinical picture: Erythematous, tender nodules on anterior shins; also seen on thighs, lateral aspects of lower legs, arms, and face, bilateral, symmetrical. Often accompanied by fever, chills, malaise, and leukocytosis.
15 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
70% have associated arthropathy, mainly with the knee joints and the ankle joints. Occurs at any age, but most prevalent between 20 and 30 years of age, adolescence and young adult. Results from immunologic reaction triggered by drugs, benign and malignant systemic illness, bacterial, viral, and fungal infections
Causes: The most common cause is post-streptococcal infection. (Important) SHOUT BCG: Sarcoid, Sulfa drug, Strep. Histoplasmosis. Oral contraceptives (The most common drug), pregnancy Ulcerative colitis TB Bechet’s Crohn’s GI infections (Yersinia, salmonella)
Work-up: o Hx (exclude drugs; sulfa antibiotic and OCP, hx of infection & GI symptoms) o CBC, diff. o ESR o Throat swab (for streptococcal infection, remember it’s the most common cause). o ASO titre; Anti-Streptolysin O (for streptococcal infection too, because it is increased in it). o CXR (for TB). o PPD. o Stool for occult blood.
Hisotology: Septal panniculitis without vasculitis. (panniculitis is inflammation of subcutaneous adipose tissue)
Treatment: self limiting disease, treat the underlying cause. o Spontaneous resolution usually occurs within three to six weeks without scarring. o NSAIDs such as indomethacin or naproxen. o Rarely do we give systemic steroids; it is effective in severe cases and can be dangerous if infection is etiology. o Potassium iodide 400 to 900 mg daily
16 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Pyoderma Gangrenosum (PG): This is the classical 1.5-5% of patients with IBD develop PG. type, the ulcerative type. It present with ulcers, distinct rolled Associated with leukemia, myeloma, edges and show monoclonaL gammopathy (IgA), satellite violaceous polycythemia, chronic active hepatitis, papules that break HCV, HIV, SLE & pregnancy down and fuse with central ulcer. It has Associated with PAPA syndrome → violaceous and Pyogenic Arthritis, Pyoderma undermined borders. gangrenosum, severe cystic Acne. (Important)
May be associated with arthritis.
Four Types: o Ulcerative. o Pustular. o Bullous. (Presents with dermatological malignancy; leukemia, myeloma). o Vegetative. (The most mild form) Peristomal Pyoderma Gangrenosum.
Histology: Massive dermal edema with epidermal neutrophilic abscesses.
Work-up: o CBC diff. o Bone marrow (for hematological malignancy). o GI evaluation.
Treatment: o Treat underlying cause. o Potent topical steroids or Intralesional (IL) steroids. o Topical tacrolimus, it is an immunomodulator. o Systemic steroids. o Sulfapyridine, sulfasalzine, and dapsone. o Cyclosporine is the next choice, with 85% of reported cases responding dramatically. o Infliximab. o Other agents: thalidomide, SSKI, azathioprine, cyclophosphamide, chlorambucil.
17 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb CUTANEOUS MANIFESTATIONS OF LIVER DISEASE:
Pruritus: generalized itching especially in the presence of biliary obstruction or jaundice. (the itching is because of the bilirubin). Jaundice. Spider naevi: small telangeictatic blood vessels especially on the face and upper chest. Palmar erythema. Diffuse hyperpigmentation. Thinning of the hair and sometime loss of sexual hair in the axillae and pubic areas. Gynaecomastia. (because of hormonal imbalance) Prone to Porphyria cutana tarda. Xanthoma.
18 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Hemochromatosis: is a disorder that results in too much iron being absorbed from the gastrointestinal tract, which leads to excessive deposition of iron in the tissues; skin, pancreas, heart. Deposition of iron in the skin will lead to hyperpigmentation.
Diffuse bronzing of the skin in hemochromatosis.
CUTANEOUS MANIFESTATIONS OF RENAL DISEASE:
End stage renal disease (ESRD) and Dialysis:
1. Pruritus: the most common cutaneous manifestation of ESRD. (You have to do Urea and Electrolytes Test and LFT. urea is the cause of pruritus).
2. Half and half (Lindsay’s) nails result from edema of the nail bed and capillary network and give the proximal half of the nail an opaque white appearance, and the distal half will be erythematous.
3. Metastatic Calcification: Deposition of calcium within tissue secondary to abnormal calcium and or phosphate metabolism It can manifest in the skin as benign nodular calcifications (calcinosis cutis) or as a more serious condition (calciphylaxis) with an associated mortality rate between 60-80%.
calcinosis cutis
19 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Calciphylaxis: Calciphylaxis presents as painful purpuric plaques and retiform pupura with progression to ulceration and necrosis. Distribution of the lesions may predict prognosis; patients with acral lesions have a better outcome that those with proximally located lesions
Histological finding of medial calcification/intimal hyperplasia of small arteries and arterioles points to an abnormality of calcium/phosphate metabolism
Management of these patients includes total or subtotal parathyroidectomy (if PTH levels are elevated), wound care, and avoidance or precipitating factors. Mortality is high, it is related to Staphylococcal superinfection of ulcers with resultant sepsis. (Important).
4. Nephrogenic Fibrosing dermopathy / Nephrogenic systemic fibrosis:
Pathogenesis o Occurs in patients with renal insufficiency who have had imaging studies with gadolinium.
Clinical Manifestations o Edema, Indurations, thickening, hardening of skin with brawny hyperpigmention. o Flexion contractures, stiffening of the hands. o Pain, pruritus common. o Extremities most commonly involved, then trunk. o Affected skin is shiny, with peau d’orange appearance.
Treatment o Extracorporeal photophoresis. o Increased morbidily/mortality because of contractures, mobility problems, falls, and fractures.
20 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
5. Porphyria Cutanea Tarda (PCT): o The pathogenesis may be related to the suboptimal clearance of uroporhyrins, which acts as a photosensitizer (product of heme synthesis pathway) from the circulation, will lead to ulceration and erosion in photo sensetive areas. o Patients may present with bullae, skin fragility, photodistributed o hyperpigmentation and hypertrichosis o Pathology demonstrates a subepidermal bulla o Treatment includes phlebotomy to decrease iron load 6. Pseudo-PCT: o Similar clinical and histological findings of PCT, in setting of normal porphyrin profile. o Usually due to certain medications such as furosemide, naproxen, tetracycline, nalidixic acid, or amiodarone.
21 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
Evaluation of Patient with generalized pruritus: Generalised pruritus in the absence of a rash requires investigation and exclusion of an underlying systemic disorder. It is important to distinguish these from an underlying primary skin disease such as scabies or eczema
Causes: o Chronic Renal Disease. o Cholestasis. o Endocrine Disease: . Thyrotoxicosis – often due to increased skin blood flow which raises skin temperature. . Hypothyroidism – pruritus secondary to the dry skin. o Malignancy: . Most common association: Hodgkin’s disease and polycythemia rubra vera o HIV Infection. o Iron deficiency anemia. o Parasetic infection. Work-up: o Physical exam. (lumph nodes) o CBC, diff, Blood film. o Stool for Ova and Parasite, occult blood. o CXR. (for chronic infections) o Thyroid, renal, and liver function tests. o Drug history.
22 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb PARANEOPLASTIC DERMATOSES: They are benign dermatoses (skin eruption) that appear in relation to an internal Check the neoplasm. table in slide #70. The doctor skipped it, that’s why I didn’t put it here
Acanthosis Nigricans: Malignant acanthosis nigricans should be suspected: o In the absence of a family history, obesity, or endocrine disorders. o Abrupt onset of lesions after the age of 40-50 years. o Rapid evolution. o Involvement of atypical areas: lips, oral mucosa, palms (tripe Palms – check the Figure; It resembles the inner surface of the stomach), flexor surface of the fingers, eyelids. o It is associated with an abdominal, most often gastric adenocarcinoma in 90% of cases.
Bazex Syndrome (Acrokeratosis Paraneoplastica): o Psoriasiform dermatitis with acral distribution, over the hand and feet. There is keratosis of the fingers and toes.
23 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
o Usually precedes the diagnosis of the neoplasm by months or years. o Associated to squamous carcinoma of the upper aerodigestive tract. Sign of LESER-TRELAT: Seborrheic keratoses: benign skin eruption, presents as thickening and discoloration of the skin, it is normal with older age.
We suspect malignancy with: o Multiple lesions. o Eruptive. o Abrupt increase in number and size. o Pruritus. o Association with Acanthosis nigricans. In this case you suspect: with gastrointestinal tumors, lymphomas.
Acquired Ichthyosis: o Ichthys = fish o The scales are polyhedral, polygonal, and tightly attached to the skin. o Generalized ichthyosis. o Absence of family history. o > 20 years of age o Association with hematological neoplasms, basically: Hodgkin’s lymphoma 70%-80%, non- Hodgkin’s lymphoma, multiple myeloma
Erythema Gyratum Repens: o Rare, few cases reported. o Presents as polycyclic rings with erythema. o 100% cases associated with neoplasms: bronchial carcinoma, esophageal carcinoma. o Clinical characteristics: urticarial, wavy,concentric o erythematous bands that change in a few hours.
24 Cutaneous Manifestations of systemic diseases 428 C2 Notes Dr. Eman Almukhadeb
NEUTROPHILIC DERMATOSES: Sweet’s syndrome Pyoderma gangrenosum; associated with leukemia.
Sweet’s Syndrome (Acute Febrile Nutrophilic Dermatosis): Acute erythematous indurated plaques or nodules Upper region of the trunk, face, and upper limbs Accompanied by: o Fever o Leukocytosis-neutrophilia (histopathologically) Rapid response to systemic corticosteroids. 85% hematological neoplasms: acute myeloid leukemia, lymphomas.
Hypertrichosis Langugnosa Acquisita: • More common in women, ♀:♂ ratio 3:1 • > 40 years • Fine whitish silky hair (lanugo) • Starts on the face, later generalizes • Rapidly Progresses • Associated neoplasms: – ♀: colorectal and breast cancer – ♂: colorectal and lung cancer • In general, the neoplasm has already spread at the time of diagnosis.
CONCLUSION: SUSPECT A PARANEOPLASTIC DERMATOSIS IF: • Abrupt onset of dermatosis in advanced age. • Rapid course. • Atypical clinical presentation. • More severe skin lesions.
GOOD LUCK.. Done by: Hala Alrugaib
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