Morton's neuroma differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]

Overview

Morton's neuroma must be differentiated from other causes of pain in the forefoot such as metatarsophalangeal joint capsulitis, intermetatarsal bursitis, inflammatory arthritis of intermetatarsal joints, calluses, stress fractures, Freiberg's disease, osteomyelitis, localized vasculitis, ischemia of plantar digital artery, tarsal tunnel syndrome, rheumatoid arthritis, peripheral neuritis, synovitis, tendonitis, and avascular necrosis.

Differentiating Morton's Neuroma from other Diseases

• Morton's neuroma must be differentiated from other causes of pain in the forefoot because too often all forefoot pain is categorized as neuroma
• Since a neuroma is a soft tissue condition, an MRI should be helpful in diagnosis, however, often an MRI will be inconclusive for neuroma even though a neuroma exists
• Other conditions to consider are:
  • Metatarsophalangeal joint capsulitis/metatarsalgia
  • Intermetatarsal bursitis between the third and fourth metatarsal bones will also give neuroma type symptoms because it too puts pressure on the nerve
  • Inflammatory arthritis of joints that join the toes to the foot
  • Calluses
  • Metatarsal stress fracture
  • Freiberg's disease
  • Osteomyelitis
  • Localized vasculitis
  • Ischemia or lack of blood flow through plantar digital artery, it precedes the fibrous thickening around the nerve known as perineural fibrosis
  • Tarsal tunnel syndrome
  • Rheumatoid arthritis
  • Peripheral neuritis
  • Synovitis
  • Tendonitis
  • Avascular necrosis

Differentiating Morton's neuroma from other diseases

Disease/Condition	Underlying Etiology	Pathophysiology	Clinical presentation	Other associated features
Morton's neuroma	Improper footwear or tight shoes with tapered toe box Abnormal positioning of toes Flat feet Overpronation High foot arches High heels Gait abnormalities Forefoot problems such as: Bunions Hammer toes High-impact sports such as: Rock-climbing Ballet dancing Jogging Running Snow skiing Racquet sports Court sports	On gross pathology, characteristic findings of morton's neuroma, include: Adherent fibrofatty tissue Small, firm, oval, yellowish-white, slowly growing, palpable nodule on skin (no discoloration of skin on the top of nodule) </=2cm in size On microscopic histopathological analysis, characteristic findings of morton's neuroma include: Extensive fibrosis around and within the nerve Digital artery Thrombosis Epineural and endoneural arterial thickening/vascular hyalinization Degenerated/demyelinated axons	Symptoms of morton's neuroma include: Feeling like ''walking on a marble'' or a pebble in the shoe or bunched-up sock Most common symptom is pain in the affected area caused by pressure on the enlarged section of nerve where it passes between the metatarsal heads, and is squeezed between them Pain is persistent & has the following characteristics: Occurs mostly on weight bearing while walking or wearing shoes that squeeze the feet Occurs frequently after only a short time Affects the contiguous halves of two toes Pain tends to ease off at the night time Nature of pain maybe any of the following: Shooting Burning Stabbing Raw Gnawing Sickening sensations Numbness Parasthesia Dysesthesia (painful hypersensitivity to normal light tactile stimuli) Functional impairment Psychological distress (severely decreasing the quality of life)	Usually located at the following sites: Third intermetatarsal space most commonly (between third and fourth metatarsals) Second or fourth interspaces At the bifurcation of the fourth plantar digital nerve Fifth interspace (rarely) (first toe is usually not involved)
Metatarsophalangeal joint capsulitis/Metatarsalgia	Abnormal foot mechanics (putting excessive amount of weight bearing pressure on the ball of the foot beneath the toe joint) Repetitive foot motion exerting pressure on the ball of foot resulting in connective tissue degeneration High level of activity Tight Achilles tendon Severe foot deformities such as: Bunion Hammer toe Second toe longer than the big toe Structurally unstable high arch of foot Prominent metatarsal heads Tight toe extensor muscles Weak toe flexor muscles Hypermobile first foot bone Improper fitting footwear (women’s dress shoes, other restrictive footwear with narrow toe box) High heels High impact activities/sports without proper footwear/orthotics such as track & field running, tennis, football, baseball, & soccer Older age (thinning of foot fat pad leads to more susceptibility to pain in the ball of the foot)	Inflammation of capsule/ligaments that surround two bones, at the level of the joint (in this case, ligaments that attach the toe bone to the metatarsal bone) Inflammation from this condition will put pressure on an otherwise healthy nerve and give neuroma type symptoms	Pain, particularly on the ball of the foot Feeling like: A ''marble'' in the shoe A bunched up sock Standing on a "pea'' Swelling at the base of the toe Difficulty wearing shoes Pain while walking barefoot Crossover toe (end-stage of capsulitis)	Also referred to as ''ball-of-foot-pain'' Colloquially known as ''stone bruise'' Usually located under the 2nd, 3rd, & 4th metatarsal heads
Intermetatarsal bursitis	Trauma Rheumatoid arthritis Gout	Irritation, inflammation and secondary fibrosis of intermetatarsal bursa located distal to transverse metatarsal ligament and close to neurovascular bundles	Between the third and fourth metatarsal bones will give neuroma type symptoms because it too puts pressure on the nerve Lateral foot compression squeezes the inflammed bursa between the metatarsal heads leading to pain mimicing neuroma Mulder's sign of physical examination (squeezing the metatarsals produces the click due to enlarged & inflammed bursa)	_
Inflammatory arthritis of metatarsophalangeal joints (join the toes to the foot)
Calluses	Repeated contact, irritation, friction or grinding pressure to the skin caused by any of the following: Frequent walking Tight or ill-fitting shoes (feet callus) Dancing barefoot especially ballet (callus at the sole of foot) Playing musical or string instruments such as guitar, violin, pizzicato, strumming (fourth finger callus) Weight lifting (upper palm area callus) Rock climbing (callus of all of the fingers) Construction work Wood carving Playing video games using a controller with a poor D-pad (thumb callus) Frequent use of a writing implement ("writer's bump"-callus of the middle finger) Use of chef's knife Hiking Martial arts Weight training Rowing BMXing Chopping wood Monkey bars Tenpin bowlers (thumb and middle finger calluses) Forehead callus called prayer bump or zebiba formed by muslim prayer Diabetes Arsenic Syphilis Actinic keratosis	Callus is a toughened area of the skin which has become relatively thick and hard as a response to repeated or constant contact, grinding pressure, irritation or friction	Usually involves hands or feet Infection of callus Bleeding of callus in diabetics especially Skin ulceration Blisters (due to frequent rubbing)	Corns (clavi) are specially-shaped calluses of dead skin that usually occur on: Thin or glabrous (hairless and smooth) skin surfaces (especially on the dorsa of toes or fingers) Thick palmar skin surface Thick plantar skin surfaces
Metatarsal stress fracture
Freiberg's disease	Etiology is usually unknown or maybe multifactorial such as: Traumatic insult (either acute or repetitive injury) Vascular compromise High-heeled shoes	Vascular compromise leads to: Collapse of the subchondral bone Osteonecrosis Cartilaginous fissures	Usually invovles the second or third metatarsal heads causing: Pain Limited motion	More common in women Manifests during adolescence (most commonly)
Osteomyelitis	Common causes include: Staphylococcus aureus Streptococcus pyogenes Haemophilus influenzae Enterobacter Escherichia coli Pseudomonas Streptococcus pneumoniae Mycobacterium tuberculosis Cellulitis Septic arthritis Fracture	Entry of the organism into bone is the first step in osteomyelitis and occurs by three main mechanisms: Hematogenous seeding Contiguous spread of infection to bone from adjacent soft tissue Direct inoculation from trauma or orthopedic surgery (including prostheses)	Systemic symptoms include: Chills Headache Fatigue Anorexia Fever Malaise Local symptoms include: Pain Edema Erythema Warmth	Risk factors for osteomyelitis include: Diabetes Hemodialysis Immunocompromised patients Tuberculosis infection IV drug use Poor blood circulation Sickle-cell disease Recent trauma Orthopedic surgery
Localized vasculitis	Infectious and immune mediated diseases (anti-cardiolipin antibodies, arthus reaction, bazin disease, behcet's disease, buerger's disease, C1 esterase inhibitor (C1-INH) deficiency, cholesterol embolism,cryoglobulinemia, cutis marmorata telangiectatica congenita, degos disease, diptheria & tetanus vaccine,familial Mediterranean fever, golfer's vasculitis, hepatitis C, Hughes-Stovin syndrome, hypersensitivity vasculitis, juvenile dermatomyositis, late congenital syphilitic oculopathy, lepromatous leprosy, livedoid vasculitis,necrobiosis lipoidica, neisseria meningiditis, pancreatitis, parvovirus B19 infection, polychondritis, polymyalgia rheumatica, polymyositis, rapidly progressive glomerulonephritis, rheumatoid arthritis, sneddon syndrome, streptococcus Group A,sweet's syndrome, systemic lupus erythematosus, thromboangiitis obliterans, treponema pallidum,tuberculosis) Smoking Cancers such as: Lung cancer Pancreatic cancer Drugs (Allopurinol, amantadine, benzylthiouracil, cefaclor, cocaine,cytarabine, hydralazine, indinavir,isoniazid, isotretinoin, janumet (sitagliptin and metformin), methotrexatemetolazone, minocycline, oxaprozin, penicillamine, pergolide, phenytoin, propylthiouracil, quinidine, trazodone, trovafloxacin mesylate)	Localized inflammation of blood vessels occurs within a confined vascular distribution or a single organ is involved without any clinical evidence of generalized inflammation Inflammation can be caused by infection or cancer or immune mediated by antibodies or certain drugs	Patient feels sick Fever Weight loss Fatigue Rapid pulse Diffuse aches Diffuse pains (difficult to pinpoint) Claudication Bruit Hypertension Focal neurological deficit Rest of the symptoms depend on the organ involved such as: Nerves (shooting pain in arms & legs, numbness, asymmetrical weakness) Skin (palpable purpura, hyperpigmented areas) Joints (full–blown arthritis, arthralgia, joint swelling) Lungs (cough, shortness of breath, hemoptysis, cavities & infiltrates in lungs, pneumonia-like appearance on CXR) Kidneys (RBCs & protein in urine, renal insufficiency) GIT (abdominal pain, bloody diarrhea, intestinal perforation) Blood (anemia, increased WBCs count) Sinus, nose & ears (hearing loss, chronic sinus congestion & infection, inflammation of the nasal septum may result in the collapse/perforation of the bridge of nose) Eyes (sudden loss of vision, conjunctivitis-pink eye) CNS (headache, stroke, altered mental status, difficulty with coordination)	Birmingham Vasculitis Activity Score is a very valuable tool to find out any systemic involvement going on concurrently with localized vasculitis Can involve any organ It is often referred to as a ''Hurting disease''
Tarsal tunnel syndrome (TTS)	Anything that creates pressure in the Tarsal Tunnel can cause TTS such as: Benign tumors Cysts Bone spurs Inflammation of the tendon sheath Nerve ganglions Swelling from a broken or sprained ankle Varicose veins Flat feet Back problems with the L4, L5 and S1 regions ("Double Crush" issue)	Painful foot condition caused by compression and impingement of tibial nerve as it travels through the tarsal tunnel	Pain in and around ankles, toes, with following features: Radiation to leg, arch, or heel Occurs while operating automobiles Occurs along the Posterior Tibial nerve path Worsens and spreads after activity and standing for long periods Relieved by rest Swelling of the feet Burning sensation on the bottom of foot radiating upward Tingling (parasthesias) Numb sensations Electric shock sensations Hot and cold sensations in the feet Feeling of feet having not enough padding Burning Increased sensations in the feet Positive Tinel's sign	Also known as Posterior Tibial Nerve Neuralgia
Rheumatoid arthritis	Common causes include: Idiopathic Genetic (HLA-DR4 cluster, HLA-DR1) Environmental (smoking) Hormonal (hyperprolactinemia) Immunologic Infections (mycoplasma, epstein-Barr virus, rubella virus, porphyromonas gingivalis) Socioeconomic factors Psychological factors Lifestyle factors (obesity, poor health)	On gross pathology, following features may be noticed: Irregular surface, seen due to synovial hyperplasia Subchondral cysts(usually present at the later stage of disease) Microscopic histopathological analysis shows: Formation of new synovial blood vessels (earliest finding) Hypertrophy of synovial lining layer Infiltration of mononuclear cells Chronic inflammation with lymphocytic infiltration Pannus formation (fibrovascular tissue or granulation tissue)	Common symptoms of rheumatoid arthritis include: Joint pain involving small joints of the hands, wrist, and foot Joint swelling Morning joint stiffness classically lasting for more than an hour Decreased grip strength Generalized aching Fatigue Weight loss Depression Less commonly, involvement of cervical spine leads to neurological symptoms such as: Tingling in the arm Numbness in the arm Weakness in the arm	Conditions associated with rheumatoid arthritis include: Osteopenia Myositis Vasculitis Uveitis Scleritis Peripheral ulcerative keratitis Interstitial fibrosis Pulmonary nodules Bronchiolitis obliterans Organizing pneumonia Venous thromboembolism Pericarditis Myocarditis Congestive heart failure Atrial fibrillation Sjogren's syndrome Felty's syndrome Patients with rheumatoid arthritis may have a positive history of: Smoking Family history Autoimmune disease
Peripheral neuritis	Infection: Herpes simplex Shingles Leprosy Guillain-Barre syndrome Chemical injury Physical injury Radiation Drugs: Disulfiram, Pergolide, Vinblastine Underlying conditions causing localized neuritis (affecting a single nerve): Diphtheria Localized injury Diabetes Underlying conditions causing polyneuritis (affecting multiple nerves): Beriberi Vitamin B12 deficiency Metabolic diseases Diabetes Hypothyroidism Porphyria Infections, bacterial and/or viral Autoimmune disease, especially Multiple Sclerosis Cancer Alcoholism Wartenbergs migratory sensory neuropathy	General inflammation of the peripheral nervous system	Symptoms depend on the nerve involved and may include: Pain Paresthesia paresis Hypoesthesia (numbness) Anesthesia Paralysis Wasting Disappearance of the reflexes	_
Synovitis	It can be caused by any of the following: Chondrocalcinosis Haemophilia type A Lupus Pigmented villonodular synovitis Polymyalgia Rheumatica Rheumatoid arthritis Osteoarthritis SAPHO syndrome Systemic sclerosis Jacobs arthropathy-camptodactyly syndrome (an autosomal recessive disorder) Gout	Inflammation of a synovial membrane (line those joints which possess cavities, namely synovial joints) Long term presence of synovitis can result in degeneration of the joint	Joint pain or tenderness Joint swelling (it is a better indicator of synovitis rather than tenderness in rheumatoid arthritis) Hard lumps (nodules)	_
Tendonitis	Chronic overuse of tendons Drug side effect: Ciprofloxacin Gemifloxacin mesylate Levofloxacin Norfloxacin	Inflammation of a tendon Microscopic tears within the disorganized collagen matrix	Ache or pain locally (increased during and after activity) Local stiffness (in the area of involved tendon) Burning of the whole joint surrounding the inflammed tendon Local swelling	Common in the upper and lower limbs (including the rotator cuff attachments) Less common in the hips and torso Tendinitis of different body parts alongwith specifically involved etiological activity is given below: Tendinitis of fingers in rock climbers Shoulder tendinitis in swimmers Achilles tendinitis due to sports such as lunging & jumping Patellar tendinitis in basketball & volleyball players
Avascular necrosis	Permanent or temporary lack of blood supply to the bones due to: Trauma Non-traumatic etiologies include: Alcoholism Excessive steroid use Caisson disease (decompression sickness) Vascular compression Hypertension Vasculitis Thrombosis Damage from radiation Bisphosphonates (particularly the mandible) Sickle cell anaemia (very rarely) Idiopathic (no cause is found in some cases)	Lack of blood supply leads to death of bone tissue causing bone to collapse	Initially, it remains painless Pain in the affected joint is the first symptom especially with use or weightbearing Limp during walking (if lower extremity is involved)	Also known as: Osteonecrosis Aseptic bone necrosis Ischemic bone necrosis Common sites of involvement in the order of frequency include: Shoulder Knee Hip Epiphysis of long bones such as femur Humerus (the bone of the upper arm) Knees Shoulders Ankles Jaw

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