Connective Tissue Disorders😍

Differentiation of Connective Tissue Disorders (Broadly)

DermatoMyositis

Features

• Age Group:
• Bimodal (children, adults)

• Prognosis:
• Good in children

• Skin manifestations + Muscle symptoms (myositis)

• Associated with breast/lung/ovarian cancer

• Muscle Involvement
• Proximal muscles affected
• Difficulty: rising, lifting, removing clothes, stairs

• Mnemonic:
• Got to run (gottrun) for jogging (synthetase 1 / jo1) → with a shawl (shawl sign) and holster (Holster sign) → rash () came → cant run

Heliotrope Rash

• Confluent macular violaceous erythema /Violet/Purplish rash around the upper eyelid of a patient.

Gottron Papules

• Lesion around knuckles

• Erythematous

• violaceous

• raised papules
• Interphalangeal, distal interphalangeal, metacarpophalangeal joints

Gottron's Sign:

• Interphalangeal joint spaces, dorsum of hands

• Feature
• Confluent,
• macular,
• violaceous erythema,
• bilateral

Myositis Presentation

• Symmetrical Proximal muscle weakness seen.
• Mainly hip joint muscle weakness
• difficulty in standing up from a squatting position.
• Distal muscle weakness can be present.

• Nail bed telangiectasia - Cutaneous manifestation.

• Calcinosis cutis

Associated Risks

• There is an increased risk of the development of cancer.

• Ovarian cancer risk is increased.

Work Up

• Serology positive

• Proximal muscle weakness tests:
• CK MM levels - elevated.
• EMG
• MRI

• Myositis-specific antibodies: 
• Anti-synthetase / Anti-Jo-1 (specific)
• (If positive → Antisynthetase syndrome)
• ↑↑ risk of development of ILD.
• Specific

• These 3 antibodies are not confirmatory.
• Anti-MDA-5 (melanoma differentiation antigen) antibody present.
• Anti TIF 1 (Transcription inhibitory factor) antibody.
• Anti Mi-2 → Good Prognosis (Mission impossible good movie)
• Anti NXP-2
• A/W cancer
• Mnemonic: Got runnning → muscle pain and thalarrnu → apo MD (MDA 5) My (Mi2) Tiffin (TF1) eduth

• IOC:
• MRI guided muscle biopsy:
• Perifascicular atrophy.

Treatment

• Corticosteroids

• Methotrexate

• HCQS

Scleroderma/Systemic Sclerosis

• Sclerosis: Thickening/binding down of skin

Types

• Limited Cutaneous Systemic Scleroderma:
• Skin below elbow and knee
• Anti-centromere antibody
• Mnemonic: Limited to centre (Anticentromere)

• Diffuse Cutaneous Systemic Scleroderma:
• Proximal body
• Anti-Scl-70 (topoisomerase I)
• anti-RNA polymerase III
• Diffuse sclerosing (Scl 70) reach to top (Topisomerase)

• Anti-fibrillarin / Anti-U3 RNP:
• Prognostic for scleroderma
• → risk of RPGN/ILD/PAH

Note: Localised scleroderma

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• Morphea

• Autoimmune connective tissue disorders

• NOT a part of systemic sclerosis
• Involves skin
• Contain collagen
• No visceral organ involvement

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Clinical Scenario

• Fibrosis around blood vessels in fingertips:
• Hampers autoregulation of blood supply.

• Raynaud phenomenon.
• Early feature
• A lady in a cold environment:
• Color change in fingertips:
• White (exaggerated vasoconstriction).
• Blue (cyanosis due to less blood supply, increased deoxygenated Hb).
• Red (exaggerated vasodilation).

• Skin Presentation:
• Loss of elasticity
• Leather-like skin (fibrosis under skin).
• Salt and pepper appearance of skin.
• inability to pinch skin
• thickened/bound-down

• Other features:
• Microstomia (fibrosis in mouth, difficulty opening mouth).
• Oesophageal dysmotility (fibrosis in esophagus, causes dysphagia).

• Differentiation from achalasia cardia:
• Achalasia cardia: Loss of inhibitory control, increased LES tone.
• Scleroderma: Fibrosis in LES, relatively lesser tone, causes reflux oesophagitis.

• Lung involvement:
• Interstitial lung disease (fibrosis in lungs).
• Specific for Diffuse

• Pulmonary artery hypertension (PAH):
• Specific for CREST
• Fibrosis in pulmonary artery.
• Loud P2.
• DLCO ↓↓ lesser due to vessel wall fibrosis.

• Scleroderma crisis:
• Progressive ↓↓ kidney size.
• GFR lesser.
• RAAS activated, causing hypertension.
• Hypertensive crisis develops.
• Management: ACE inhibitors (oral).

Patient Presentation

 

• Mask-like facies:
• Loss of wrinkling,
• shiny skin,
• restricted mouth opening
• visible incisors
• furrowing along oral commissures
• telangiectasias

• Sclerodactyly:
• Bound-down hand skin, deformities (contractures) in interphalangeal joints

Limited Scleroderma (CREST Mnemonic)

• C: Calcinosis → Calcium deposit in subcutaneous space

• R: Raynaud’s phenomenon:
• DOC: Ca channel blockers like amlodipine
• start with lowest dose to prevent postural hypertension

• E: Esophageal dysmotility (dysphagia).

• S: Sclerodactyly.
• Presence of pitting scars in volar aspect of fingers due to fibrosis.

• T: Telangiectasia.

• Additional:
• Anti-centromere antibody present.

Leading cause of mortality:

• PAH > ILD
• ILD
• Lung transplantation possible
• Severe PAH (up to 60mm)
• requires heart-lung transplantation (difficult)

Phrynoderma / follicular hyperkeratosis/ Toad Skin

Without 13-cis retinoic acid:

• Earliest skin manifestation: Dryness

• Caused by Vitamin A or essential fatty acid deficiency.

• Small papillary lesions
• Dry, rough, hyperkeratotic papules
• Small keratin plug is at the tip.
• Near back of elbows, knees, joint areas

• Pathology: Impaired follicular keratinisation (Vit A essential)

Deficiency Manifestations (Pellagra)

"Broad collar" rash (Cassal’s necklace),

• Subacute eczema

• On photoexposed areas (V-area of neck, dorsum of hands)

• Hyperkeratotic, lichenified, eczematous patches

• Neck: Castle's Necklace

Treatment

• High-protein diet

• Niacin or Nicotinamide.

Acrodermatitis Enteropathica

 

 

 

• Autosomal Recessive

• Daily requirement: 5–10 mg/day

Types of Zinc Deficiency

1. Congenital:
• Autosomal recessive (Zip4 transporter protein deficiency).
• After 6 months / weaning (maternal milk aids zinc absorption)

2. Acquired: Chronic alcoholics

Main Features (DDA Mnemonic)

• Dermatitis
• acral, periorificial
• Presents with extensive inflammatory rashes
• oral cavity,
• genital region.
• Rash distribution:
• Cheeks
• Mouth
• Anal region

• Diarrhoea

• Alopecia

• Mnemonic: Z → vayil kude keri appi pokunnath

Treatment:

• Zinc supplementation

Kveim’s test:

• Skin test

Skin Presentation

• Non-specific features (e.g., Erythema Nodosum)

• Specific skin lesions:
• Red-brown papules with normal surface (no scaling, crust, ulcer)

Lupus Pernio:

• Red papules with normal surface on nose, cheeks (sometimes telangiectasias)

Angiolupoid Sarcoidosis:

• Erythema, telangiectasias limited to specific area

 

Dermoscopy: 

• Apple jelly nodules

Treatment for Skin lesions

• Antimalarials (specifically HCQS)

Histology (Sarcoidosis Granuloma)

• Mnemonic: Saratha (Sarcoidosis) → Naked (Naked) Nun (Non caseating) Showing (Shaumann) Ass (Asteroid body)

Features	Notes
Non-caseating > Caseating	Surrounded by lymphocytes / giant cells
Naked granulomas.	Absence of lymphatic collar Sparse perigranuloma infiltrate
Epithelioid cells:	Contain slipper-shaped nuclei
Inclusion Body	ㅤ
↳ Asteroid	• Star shaped • intracellularly (inside giant cells). • Also seen in sporotrichosis ↳ but → extracellular. • Mnemonic: Rose gardener roams outside, so star is outside
↳ Schauman	• Round bodies → Basophilic calcium concretions • Hypercalcemia

Vasculitis - Henoch-Schönlein Purpura (HSP)

Case Scenario

• A child presents with abdominal pain, hematuria, and palpable purpura over the leg.

• Small vessel vasculitis

• Often preceded by infections/drugs

Diagnostic criteria

• Palpable purpura with presence of 1 or more of:
• Diffuse abdominal pain
• Arthritis or arthralgia
• Any biopsy showing IgA deposition
• Renal involvement

Organs affected (PAARpura):

• P → Purpura (commonly on lower limbs).

• A → Arthralgia.

• A → Abdominal pain.
• Complication - intussusception
• Submucosal hematoma
• Main indication for giving steroid → GI bleed

• R → Renal involvement (e.g., hematuria).
• Kidney is the most common affected organ.
• Glomerulonephritis is seen in 1/3 of patients.
• Proteinuria
• haematuria,
• RBC casts

Biopsy:

• Leukocytoclastic vasculitis with IgA-containing immune complexes

Skin Presentation:

• Palpable purpura (felt)
• Thrombocytopenia is Absent.

• Lower legs and buttocks

• Painful

Treatment:

• Most of the cases are self-limiting.

• if not self-limiting
• DOC: Corticosteroids
• Dapsone
• Colchicine

NOTE:

• Palpable purpura → Vasculitis

• Non palpable purpura → Bleeding, clotting, thrombocytopenia

Mnemonic:

• So (Psoriasis) So (Spondylitis) So (Sacroilitis) U (Uveitis)

• UV () Sar () Gange () nodu Sorry (psoriasis) paranju ()

 

• Systemic vasculitis

• Anti alpha enolase Ab

• Pathergy → Pathetic diagnosis → misunderstood young patient with recurrent oral and genital ulcers

• Misunderstood a young as 51 () yr old nolan (Enolase) in bus ()

Triad of Features

• Relapsing uveitis (mainly posterior)

• Recurrent genital ulcers

• Recurrent oral ulcers

Features (Oro-Oculo-Genital Syndrome)

• Most common diagnostic feature:
• Recurrent oral ulceration.
• Painful, like aphthae, recurrent
• Recurrence at least thrice in any 12 months.

• PLUS TWO OF:
• Genital ulcers:
• Female: Vulva ulcer
• Male: Scrotal ulcer
• not penile ulcer as in STDs like H. ducreyi, syphilis
• Eye lesions:
• Anterior uveitis.
• Posterior uveitis.
• Hypopyon
• Retinal vasculitis
• Skin lesions:
• Erythema nodosum
• Pseudofolliculitis or papulopustular lesions, OR
• Acneform nodules in post-adolescent patients not on corticosteroids.
• Positive pathergy test

Other Systemic Involvement:

• Non-erosive, asymmetric oligoarthritis

• Multi-system: Pulmonary, cardiac, GI, neurological

Pathergy Test/ Pathergy phenomenon:

• Positive because it can cause systemic vasculitis

• Not a diagnostic criteria

• Type 4 Hypersensitivity reaction

• Procedure:
• Sterile needle puncture on forearm with hypodermic cutting edge.

• Normal response:
• bleeding, clotting, mark disappears in 2-3 days.

• Behcet’s response:
• After 48 hours, formation of sterile pustule

Complications:

• Pulmonary artery aneurysm possible.
• Rupture: Lethal complication.
• Note: Pulmonary artery not involved in polyarteritis nodosa.

Management:

• Corticosteroids

• Ocular involvement:
• Azathioprine.

Mnemonic:

• Bus on a path → Pathergy test

• Oro occulo genital → On bus

Reactive Arthritis (Reiter's Disease)

• HLA Association: HLA-B27 and B51

Definition

• *Joint inflammation caused by sterile inflammation reaction
• following a recent entropathic or urogenital infection**.

Triggered by:

• GI infection,

• non-gonococcal urethritis (sexually acquired reactive arthritis),

• HIV patients

Triad of Features

Mnemonic:

• Cant see
• Conjunctivitis (non-gonococcal, esp. Chlamydia)

• cant pee
• Urethritis
• Circinate Balanitis:
• Superficial erosions on glans/penis

• cant climb a tree
• Polyarthritis:
• >1 month,
• non-suppurative,
• lower limbs (post GI/urethritis infection)



• Keratoderma Blennorrhagicum:
• Hyperkeratotic papules on palms and soles

Treatment

• Physical therapy and rehabilitation.

• NSAIDs.

• Intra-articular steroid injection in severe cases.