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Medscape
22-07-2025
- Health
- Medscape
Uncontrolled Movements, Anger, and Insomnia
Editor's Note: The Case Challenge series includes difficult-to-diagnose conditions, some of which are not frequently encountered by most clinicians, but are nonetheless important to accurately recognize. Test your diagnostic and treatment skills using the following patient scenario and corresponding questions. If you have a case that you would like to suggest for a future Case Challenge, please email us at ccsuggestions@ with the subject line "Case Challenge Suggestion." We look forward to hearing from you. Background A 35-year-old man presents to the neurology clinic due to abnormal movements over the past 6 years. The involuntary movements began in the right upper limb, followed sequentially by the left upper limb, left lower limb, and finally the head and neck. The movements occur during wakefulness and are absent in sleep. They are described as jerky and nonpurposeful. His gait has assumed a dancelike character. He also has had behavioral changes that include frequent outbursts of anger, aggressive behavior, depressive mood, and insomnia. His abnormal movements are aggravated during outbursts of anger and disturbances in mood. He has no weakness in any limbs but is unable to perform regular household activities. Family members have also noted memory impairment. He has been unable to continue his work as a machine operator for the past 3 months. He has no history of psychoactive drug intake, including phenytoin, phenothiazines, haloperidol, L-dopa, lithium, isoniazid, amphetamines, tricyclic antidepressants, or any other relevant drugs. He reports no history of chest pain, breathlessness, or joint pain. His family history includes a paternal grandfather and father who had similar forms of abnormal movements and died at the age of 60 years and 55 years, respectively. The patient has five siblings (two brothers, three sisters). His elder brother died by suicide at age 25 years, and his elder sister died at age 33 years. Both had abnormal movements and abnormal behaviors. One of his younger sisters (age 22 years) also has similar abnormal movements and depressed attitude. His younger brother (age 17 years) and other younger sister (age 14 years) are healthy and symptom-free. The patient's children, an 8-year-old son and a 10-year-old daughter, are symptom-free. His past medical history is positive for hypertension, which is well controlled with lisinopril (20 mg daily). He has no surgical history. He does not smoke, drink, or use recreational drugs. Physical Examination and Workup A general examination reveals a pleasant man who is well built and in no acute distress. His blood pressure is 140/80 mm Hg, his heart rate is 78 beats/min, his respiratory rate is 12 breaths/min, his SpO 2 level is 98% on room air, and his body mass index (BMI) is 20. He is afebrile. A cardiovascular examination reveals normal peripheral pulses and normal heart findings. A chest examination reveals normal auscultation and expansion. His abdomen is soft. Head, eyes, ears, nose, and throat (HEENT) examination findings are unremarkable. He does not have a skin rash. A visual examination reveals normal acuity, field, and fundi. His affect is flat. A neurologic examination of the higher mental functions reveals that the patient is awake and alert, with normal orientation, attention, concentration, fund of knowledge, and language function. His memory is impaired, with recall one-third at 3 minutes. He has a normal past memory. His speech is normal. A cranial nerve examination reveals normal extraocular movements, increased blink rate, normal facial sensation, a symmetric face with abnormal fidgety movement, normal hearing, and normal palate movement. He has abnormal tongue movement and cannot protrude his tongue more than 20 seconds (darting tongue movement). He has normal shoulder shrug. No Kayser-Fleischer ring is noted during slit-lamp examination. An examination of the motor system reveals decreased muscle tone, normal bulk, and 5/5 strength in both upper and lower extremities. No atrophy or fasciculation is noted. Deep tendon reflexes are normal (2+ with flexor planters). Sensory examination findings are normal. Finger-nose test findings are normal. An examination of the extrapyramidal system reveals reduced tone and involuntary choreoathetoid movements that affect both upper and lower extremities as well as his face. He has a dancing gait. Diagnostic tests reveal normal complete blood cell count (CBC) and comprehensive metabolic panel findings. He has normal serum findings and urine copper levels. His erythrocyte sedimentation rate (ESR) is 22 mm/hr (reference range, 0-22 mm/hr). He has normal ECG findings, a normal thyroid-stimulating hormone (TSH) level, a normal transthoracic echo (with ejection fraction 65%), and normal chest radiography findings. Brain MRI can be used to evaluate for selective atrophy of deep gray structures, to document disease burden, and to provide a baseline for future comparison. Whole-body 18-FDG PET/CT may be used to screen for occult neoplasm and paraneoplastic chorea, but this is exceedingly rare and typically subacute. NMDA receptor antibody panel may be used to investigate for autoimmune encephalitic chorea, but the features of this (ie, seizures, psychosis, and autonomic instability) are absent in this case. RPR and FTA-ABS may be used to evaluate for neurosyphilitic chorea, but this is also very uncommon and unnecessary without risk factors or acute symptoms. In this patient, brain MRI reveals evidence of bilateral caudate atrophy, with increased intercaudate distance (Figure). Figure. Cerebrospinal fluid (CSF) examination findings are normal. Discussion This 35-year-old man has Huntington disease. He has insidious-onset, slowly progressive movement disorder, and movements are absent during sleep. His movements are described as choreoathetoid. He has family history that suggests autosomal dominant transmission. Apart from the movement disorder, he also has neuropsychiatric manifestations, with death at an early age in the family. A CT scan of the head revealed evidence of caudate nucleus atrophy. Brain MRI revealed evidence of caudate atrophy (Figure). Figure. In evaluating the differential diagnoses, the patient has no history of antipsychotic medication use to suggest tardive dyskinesia. He has no clinical or diagnostic evidence of infection or heart involvement, which makes Sydenham chorea unlikely. No acanthocytes were observed, helping to exclude neuroacanthocytosis. The strong family history of progressive abnormal movements and neuropsychiatric symptoms across generations supports a genetic etiology, specifically autosomal-dominant Huntington disease. Huntington disease is a rare neurodegenerative disorder of the central nervous system (CNS) characterized by choreiform movements, behavioral and psychiatric disturbances, and dementia.[1] Huntington disease is caused by an autosomal-dominantly inherited expansion of CAG trinucleotide repeats in the huntingtin ( HTT ) gene on chromosome 4; this leads to production of a mutant huntingtin (mHTT) protein, with an abnormally long polyglutamine repeat.[2] Individuals with more than 39 CAG repeats develop the disease, whereas reduced penetrance is seen in those with 36-39 CAG repeats. The disease can be anticipated when the gene is passed down the paternal line, as in this case; a father with a CAG repeat length in the intermediate range may have a child with an expanded pathogenic repeat length. This is because sperm from males shows greater repeat variability and larger repeat sizes than somatic tissues. Mutant huntingtin protein leads to death and neuronal dysfunction through various mechanisms. Postmortem studies reveal diffuse atrophy of the caudate and putamen. The progressive worsening of Huntington disease leads to a bedridden state with cognitive deterioration, and death typically occurs about 20 years after the onset of symptoms.[3] Prevalence in the white population is estimated at 1 in 10,000 to 1 in 20,000. The mean age at symptom onset is 30-50 years. In some cases, symptoms begin before age 20 years, with behavior disturbances and learning difficulties at school; this is termed juvenile Huntington disease (Westphal disease).[4] The first description, by Waters, dates to 1842. However, after a description in 1872 by George Huntington, it became known as Huntington chorea. In 1983, a linkage on chromosome 4 was established, and in 1993 the gene for Huntington disease was found.[1] Diagnosis of Huntington disease is confirmed by demonstration of autosomal dominant transmission or gene testing in the presence of clinical features.[5] The clinical features of Huntington disease consist of motor, cognitive, and neuropsychiatric manifestations. Huntington disease has a biphasic course of hyperkinetic phase with chorea in the early stages of disease that then plateaus into a hypokinetic phase, consisting of bradykinesia dystonia, balance issues, and gait disturbance. The younger-onset variant is associated with predominant bradykinesia.[6] Cognitive disturbance can be seen many years before other symptom onset and is characterized by impaired emotion recognition, processing speed, and executive function abnormality. Neuropsychiatric symptoms widely vary, including apathy, anxiety, irritability, depression, obsessive-compulsive behavior, and psychosis. A lack of awareness of early and progressing behavioral, cognitive, and motor symptoms is a hallmark of Huntington disease. This unawareness is caused by the disease itself (specifically, impaired insight or anosognosia) and is not the result of intentional denial, avoidance, or suppression of symptoms.[7] Therefore, a comprehensive history, including information from a knowledgeable family member/caregiver, is advisable.[7] Numerous conditions can mimic Huntington disease, including a spinal cerebellar ataxia 17, spinocerebellar ataxia 1-3, and Friedreich ataxia, which involve neuropathy. If seizures are also present, dentatorubropallidoluysian atrophy should be considered. Acanthocytes are seen in patients with neuroacanthocytosis.[8-10] Isolated chorea can be seen in acquired conditions, including chorea gravidarum, systemic lupus erythematosus, antiphospholipid syndrome, thyrotoxicosis, postinfectious syndromes, polycythemia vera, and some drug use. Genetic testing for the mHTT mutation can be either diagnostic or predictive.[6] A diagnostic test may be performed when a patient presents with typical motor features of Huntington disease. Prior to testing, the patient should be informed about Huntington disease and its hereditary nature, as a positive test result has implications for the patient and family. Predictive testing is performed in asymptomatic patients, mostly for reproductive reasons. Treatment of Huntington Disease The optimal management of Huntington disease involves a multidisciplinary approach that includes neurology, nurses, physical therapy, speech-language pathology, and dietitians and other healthcare professionals. The goal is to optimize the quality of life based on the changing need of the patient. These consist of combined pharmacologic and lifestyle changes, including behavioral therapy. Symptoms may be worsened by stress, fatigue, and intercurrent disorders (eg, anxiety, digestive disorders, infectious or painful conditions), so these aspects must be assessed and treated alongside the primary symptoms of Huntington disease.[3] In clinical practice, information about symptoms should be obtained from both the patient and caregivers, since patients may have impaired awareness of their condition.[11] Identifying coexisting psychiatric symptoms, comorbid medical conditions, and environmental factors is crucial.[11] Educating caregivers about the nature and presentation of symptoms and methods to modify triggers is also vital.[11] Medication choices should be guided by coexisting symptoms and disease stage, and regular reassessment of drug need and potential for dose reduction is important because of adverse effects that can mimic disease progression.[11] Nonpharmacologic interventions, including behavioral therapies and environmental modifications, should be prioritized for neuropsychiatric symptoms in Huntington disease. Pharmacologic agents may be considered if these measures are insufficient, and consultation with a psychiatrist knowledgeable in Huntington disease is recommended for individuals whose symptoms are resistant to standard pharmacologic therapy.[11] Tetrabenazine and its modified version, deutetrabenazine, are commonly used to treat choreiform movements. Side effects of tetrabenazine can include depression, anxiety, sedation, sleep problems, restlessness, and parkinsonism.[7] Citalopram is a selective serotonin reuptake inhibitor used to manage depression. Modafinil and atomoxetine are used to manage apathy. Tiapride, although unavailable in the United States, is considered a first-line treatment option for chorea outside the United States.[7] Other antipsychotics such as olanzapine, risperidone, and quetiapine are also used to manage chorea. Risperidone may also help with psychomotor restlessness, and olanzapine and quetiapine can have additional benefits like weight gain (which can be desirable in Huntington disease) and mood stabilization. Haloperidol has also shown effectiveness.[7] Medications used to suppress chorea (eg, tetrabenazine and deutetrabenazine and certain antipsychotics) should be used sparingly and mainly for subjectively disabling hyperkinesias, starting at low doses and titrating gradually. They make take 4-6 weeks to show results.[7] The choice of medication depends on the individual patient's symptoms, tolerability, and co-existing conditions.[7] Evidence regarding the treatment of psychiatric symptoms in Huntington disease is limited, with recommendations often based on expert opinion owing to a lack of robust controlled studies.[7,11] Nonpharmacologic interventions such as cognitive-behavioral therapy and psychodynamic therapy are recommended, especially for depression, anxiety, obsessive-compulsive behaviors, and irritability. Behavioral strategies (eg, structured routines and distraction) are important for managing irritability and agitation.[3,11] Depression: Selective serotonin reuptake inhibitors (SSRIs) such as citalopram, fluoxetine, paroxetine, sertraline, and venlafaxine are recommended as pharmacologic options. [3,7] Mianserin (unavailable in the United States) or mirtazapine are alternatives, particularly in patients with sleep disruption. [3,7,11] Electroconvulsive therapy (ECT) may be considered for severe or resistant cases, although it can significantly impair short-term memory. [3,7] Mianserin (unavailable in the United States) or mirtazapine are alternatives, particularly in patients with sleep disruption. Electroconvulsive therapy (ECT) may be considered for severe or resistant cases, although it can significantly impair short-term memory. Anxiety: SSRIs or serotonin-noradrenaline reuptake inhibitors (SNRIs) are first-line treatments, especially when anxiety coexists with depression. [3,11] Mirtazapine is an option in patients with sleep disorders. [11] Long-term use of benzodiazepines is generally discouraged for ambulatory individuals because of the risk of falls and dependence but can be used short-term or as needed. [3,11] Mirtazapine is an option in patients with sleep disorders. Long-term use of benzodiazepines is generally discouraged for ambulatory individuals because of the risk of falls and dependence but can be used short-term or as needed. Obsessive-compulsive behaviors/perseverations: For true obsessive-compulsive phenomena, SSRIs are considered first-line treatment. [3] Olanzapine and risperidone may also be valuable for ideational perseverations, particularly if associated with irritability. [3] Clomipramine is an option, especially if needed for coexisting obsessive perseverative behaviors. [11] Olanzapine and risperidone may also be valuable for ideational perseverations, particularly if associated with irritability. Clomipramine is an option, especially if needed for coexisting obsessive perseverative behaviors. Irritability and aggression: SSRIs are a first-line treatment. [3] For aggressive behavior, neuroleptics are recommended. [3,7] Mood stabilizers (eg, valproate, lamotrigine, lithium, carbamazepine) can be added if irritability is resistant to other treatments or for mood lability. Risperidone and olanzapine may help reduce irritability. [3,7] For aggressive behavior, neuroleptics are recommended. Mood stabilizers (eg, valproate, lamotrigine, lithium, carbamazepine) can be added if irritability is resistant to other treatments or for mood lability. Risperidone and olanzapine may help reduce irritability. Psychosis (hallucinations/delusions): Second-generation neuroleptics (antipsychotics) are the first-line pharmacologic treatment. [3,7,11] Options include olanzapine, risperidone, quetiapine, aripiprazole, and haloperidol. [7] Clozapine may be considered for severe or resistant cases, particularly in akinetic forms of Huntington disease but requires regular monitoring. [3,7,11] Underlying causes, such as the use of psychotropic agents or somatic triggers, should be investigated and addressed. [3,11] Options include olanzapine, risperidone, quetiapine, aripiprazole, and haloperidol. Clozapine may be considered for severe or resistant cases, particularly in akinetic forms of Huntington disease but requires regular monitoring. Underlying causes, such as the use of psychotropic agents or somatic triggers, should be investigated and addressed. Apathy: Personalized cognitive stimulation and structured routines and activities are recommended.[3,7,11] If depression is suspected as a contributor, an SSRI should be tried.[3,11] In patients without depression, activating antidepressants or stimulant drugs (eg, methylphenidate, atomoxetine, modafinil) may be considered.[11] Sedative medications may increase apathy, so their dosage should be monitored or reduced.[3,11] Currently, no pharmacological treatment is specifically recommended for cognitive symptoms in Huntington disease.[3,7] Rehabilitation strategies, including speech therapy, occupational therapy, cognitive and psychomotor therapy, may help transiently improve or stabilize cognitive functions.[3,7] Coping strategies can be useful as an alternative to medication. Certain medications, such as sedative drugs, neuroleptics, and tetrabenazine, can negatively affect memory, executive functions, and attention.[3] Apart from symptomatic treatment, pharmacologic agents have failed to show benefit in clinical trials as disease-modifying agents. The most promising approaches in regard to disease modification are emerging therapies aimed at lowering levels of mHTT by targeting either the DNA or RNA of the mHTT gene.[12] RNA-targeting using antisense oligonucleotides (ASOs) have shown disappointing results in clinical trials. This has shifted significant research focus and toward orally available small molecules that modify HTT mRNA splicing, thereby reducing mHTT protein production. DNA-targeting approaches using gene editing tools like CRISPR/Cas9, while demonstrating success in preclinical models, remain in the early stages of development.[13,14] The patient in this case was diagnosed with Huntington disease with CAG repeat 78. He was started on tetrabenazine for abnormal movements and citalopram for depression. He opted to apply for federal disability. His children are asymptomatic, and the family decided not to investigate until symptoms develop or they are age 18 years.
Medscape
14-07-2025
- Health
- Medscape
Athlete's Puzzling Toe Ailment
Editor's Note: The Case Challenge series includes difficult-to-diagnose conditions, some of which are not frequently encountered by most clinicians, but are nonetheless important to accurately recognize. Test your diagnostic and treatment skills using the following patient scenario and corresponding questions. If you have a case that you would like to suggest for a future Case Challenge, please email us at ccsuggestions@ with the subject line "Case Challenge Suggestion." We look forward to hearing from you. Background and Initial Presentation A 36-year-old woman presents to the clinic with a longstanding nail complaint (1-2 years' duration). She is otherwise healthy and reports aching pain and tenderness surrounding her right great toenail that has been worsening over the last year. The immediate proximal skin of the toe has signs of inflammation and redness. The surrounding tissue is not draining fluid or bleeding. The toenail itself has yellow discoloration and a thickened appearance with a pattern similar to that of an oyster shell. She notes that her nail appears to grow in horizontal layers but seems to have stopped growing over time. She no longer feels the need to clip its end. She reports discomfort during exercise and periods of walking or running. All her other toenails and fingernails are unaffected. She denies any personal or family history of nail issues or psoriasis. She regularly hikes and goes for long runs and has worn the same brand of running shoes for many years. She wears shoes of "medium" width and Converse brand shoes when lifting weights. She says that these shoes sometimes feel tight-fitting and often apply pressure to her toes while exercising. Her pain, tenderness, and swelling of the proximal nailfold began around 1-2 years ago and have gradually become more bothersome. She also reports that she began noticing abnormal-appearing nail growth several months before the initial onset of symptoms. She cannot recall any specific major traumatic incident involving the nail around that time. Another healthcare provider, who presumed a case of onychomycosis (toenail fungus), had prescribed a topical antifungal treatment to use twice daily. She had also tried other topical therapies, including an antibiotic ointment and petroleum jelly, in addition to a course of oral antibiotics. None of these treatments significantly improved her condition. She is most bothered by the discomfort she feels while doing physical activity, as she is an avid runner and hiker. Physical Examination and Workup A thorough physical examination using a dermatoscope revealed xanthonychia (yellowing of the nail), along with a thickened longitudinal curvature (Figure 1) and marked onycholysis (separation of the nail plate from the nail bed). Paronychia (inflammation) and erythema (redness) of the proximal nail fold were also observed. The cuticle appeared to be absent. These signs suggest an issue that interferes with proper nail growth and indicates that infection, trauma, or irritation to the periungual tissues has occurred. No visible signs of infection were observed on clinical examination. A nail clipping for dermatopathology was also performed to rule out fungal involvement, since a previous healthcare provider had not performed laboratory work but rather treated empirically with a topical antifungal. Dermatopathology results were negative for fungal involvement. Retronychia is typically diagnosed based on clinical examination and dermoscopy, which reveal features such as proximal paronychia, a thickened and layered nail plate, onycholysis, and an absent cuticle. The diagnosis is supported by a thorough patient history and may be confirmed by excluding similar conditions such as onychomycosis or nail psoriasis through nail clipping and dermatopathologic analysis. Retronychia can also be diagnosed based on ultrasonography if more than two overlapping nail plates are present, blood flow is increased through the dermis of the proximal nailbed and posterior nailfold, the distance between the nail plate's origin and the base of the distal phalanx is decreased, and echogenicity is decreased.[1,2] While rarely performed in everyday practice, ultrasonography is a noninvasive examination that allows for clear visualization of the nail and underlying tissue.[1,3] This can help to rule out potential tumors and other possible complications. It is particularly useful for observing clinical changes consistent with nail psoriasis.[4] Conventional radiography can be used in the initial investigation for bone and joint deformities or bony outgrowths associated with trauma or suspected tumors. However, other imaging modalities (eg, ultrasonography) would be more appropriate for this patient.[5] Retronychia is an underreported and underdiagnosed condition in dermatology. Case studies in research and literature are limited. Symptoms of retronychia can mimic other more commonly recognized nail disorders involving inflammation of the proximal nailfold. Individuals with retronychia may endure a prolonged duration of symptoms before seeking treatment, which can further confound the clinical diagnosis. While retronychia primarily affects adults, it can occur in all ages.[6] It is more common in women than in men, partially owing to the choice and fit of footwear. Shoes with narrow toe boxes limit the forefoot's range of motion and predispose feet to loading stress. Women tend to wear shoes with longer lengths to compensate for the lack of width or depth that their feet need, in addition to wearing shoes with elevated heels more regularly than men. This can exacerbate foot pathology and pain, such as corns and calluses, as well as nail disorders like retronychia.[7] Pathophysiology of Retronychia Retronychia is a chronic inflammatory condition characterized by ingrowth of the proximal nail plate toward the proximal nailfold.[8] Retronychia results from misaligned nail growth and multiple generations of nail plate localization beneath the initially damaged nail.[1] When the toe experiences repetitive microtrauma or a major traumatic event, the growing nail loses support from the nailbed but remains adhered laterally to the nail matrix or abnormally to the distal nail bed, forcing continued misalignment between the nail plate and nail matrix. Newly growing nail plates become embedded in the proximal nail fold, and old nail plates are unable to be properly shed.[3] The nail unit thus remains unstable and susceptible to further microtrauma, which perpetuates the cycle of nail plate layering.[9] Figure 1. Retronychia of the great toenail, seen on the right (patient's left toe). The nail surface appeared in a horizontal layered pattern, likely an indication of generations of nail being repetitively pushed backward into the nail matrix and causing the nail to "stack" in layers. In retronychia, the old nail plate becomes misaligned with the nail matrix, preventing it from becoming pushed out as new nail plates grow. Distal onycholysis perpetuates the cycle of nail dystrophy by reducing the surface area of the anchored nail, which can lead to gradual longitudinal shortening of the nail bed.[10] The nail thus becomes continuously destabilized from the matrix and more prone to backward displacement with trauma. In long-term retronychia, the formation of a distal bulge can manifest as another consequence of continuous backward pressure on the nail and often contributes to the progression, maintenance, and relapse of retronychia (Figure 2).[1,8] Granulation tissue may form under the proximal nailfold, particularly in more advanced cases.[2] The cuticle often appears to be absent, and proximal nail fold inflammation and erythema are frequently observed. > Figure 2. The vast majority of retronychia cases result from trauma (isolated incident or repetitive microtraumas) and ill-fitting footwear.[1] Regular physical activity is another underlying factor observed in many cases. Ischemic etiologies that contribute to nail dystrophy may also be linked to retronychia by precipitating disrupted nail matrix growth. Some conditions hypothesized to fall under this category are compartment syndrome and thrombophlebitis.[11] Furthermore, individuals with static disorders of the foot may be predisposed to retronychia.[11] Congenital malalignment of the great toenail (lateral deviation of the nail plate), reflex compensatory hyperextension of the halluces, and an Egyptian foot type (characterized by a longer great toe and shorter second toe) are podiatric conditions that can increase stress on the great toe and make it more susceptible to trauma. They also seem to be encountered more often in practice than they are reported.[11] Potential hereditary factors and static disorders of the feet should therefore be accounted for in the management of retronychia to prevent relapse. Retronychia may cause varying symptom severity, affecting motivation to seek treatment. The earlier the diagnosis is made, the less likely recurrence will occur and the higher success rate treatment interventions will yield. Differential Diagnoses Retronychia can often be mistaken for onychomycosis, as both conditions share similar manifestations of yellowing discoloration and thickening of the nail plate.[12] Onychomycosis is common, constituting 40%-50% of all nail disorders, making clinicians more likely to mistake retronychia for onychomycosis in its early stages.[13] Since no fungus was detected in the tested sample, antifungal therapies would be ineffective in treating this patient's condition. Collecting a nail clipping for dermatopathology, in conjunction with dermoscopy, can also be helpful in ruling out nail psoriasis, another common misdiagnosis of retronychia. Nail psoriasis is frequently characterized by pitting of the nails, onycholysis, red spots in the lunula, subungual hyperkeratosis (which can also be seen in retronychia), and oil or salmon patches.[13] Nail psoriasis more often affects the fingernails, whereas retronychia primarily affects the toenails — particularly the great toenails. Retronychia can also manifest similarly to onychomadesis or Beau lines.[10] Both nail dystrophies involve a disruption to nail growth following some type of insult to the nail matrix. Beau lines appear as parallel ridges or grooves across the nail plate due to slowed nail plate production. Onychomadesis, a more severe form of Beau lines, is the proximal separation of the nail plate from the nailbed associated with cessation of nail plate growth from the matrix.[14] Drugs, specifically chemotherapeutic agents, are one of the most common causes of Beau lines, while infections are a more common cause of onychomadesis.[14] Both onychomadesis and retronychia are linked to chronic repeated trauma. In onychomadesis, however, the old nail plate separates from the nail bed but remains aligned with the nail matrix, allowing the new nail plate to gradually push out and replace the old one. The prognosis is usually promising.[15] Onychorrhexis is characterized by longitudinal ridging or splitting of the nail plate due to fragility, often seen in conditions such as lichen planus, aging, nutritional deficiencies, or systemic disease. Retronychia typically affects one or both great toenails and is far less common in other toes or fingernails.[15] The great toes are more susceptible because of their exposure to repeated trauma from bearing body weight and experiencing continuous pressure during walking, standing, or exercising. Early stages of retronychia are characterized by cessation of nail growth, xanthonychia, and mild acute paronychia with associated pain. Late stages involve the classic layered nail plate, along with onycholysis of the distal nail and subungual hyperkeratosis (buildup of keratin under the nails).[1] Purulent discharge is not seen in retronychia. It suggests an infectious etiology. The patient in this case experienced mild pain and discomfort that gradually worsened over time. In some cases of chronic retronychia, however, pain may be minimal or entirely absent.[9] Treatment for retronychia depends on the severity of symptoms at the time of diagnosis and the patient's motivation to treat. Conservative treatment methods involve high-potency corticosteroids in topical (eg, clobetasol propionate) or intralesional (eg, triamcinolone acetonide) preparations. These can be used to target paronychia in the proximal nailfold for mild-to-moderate cases.[15] Intralesional corticosteroid injections show promising results, with one study showing a definitive cure in 27 of 28 patients in an "intermediate stage" of retronychia after three rounds of once-monthly triamcinolone acetonide injections.[6] A third steroid injection was warranted in only 4 of 28 of patients. Nail plate discoloration, proximal nail fold discharge, and nail elevation significantly improved after just one session, and cessation of nail growth improved after the second. Other conservative treatment options include consistent taping to alleviate some pressure and promote regular nail growth. Additionally, wrapping the affected toe in a protective foam tube may lessen further microtrauma and prevent relapse of symptoms.[8] Recurrence is always a risk with conservative treatment. Nonconservative treatment entails surgical intervention — specifically proximal or complete nail plate avulsion. Superimposed nail plates can be removed, and granulation tissue can be excised with this method.[11] This remains the treatment of choice for chronic or end-stage cases of retronychia that do not respond well to conservative treatments. Patients undergoing this procedure should experience pain relief and prompt healing, and the new nail plate is expected to grow back normally (Figure 3). Mild postoperative nail dystrophy is a risk, but it is rare.[11] Examples include retraction of the nail bed with pincer nail, hypertrophy of periungual tissues, and micronychia.[2] In cases with severe pain or nailfold hypertrophy, nail surgery can be performed with the DuBois (for mild-to-moderate cases) or super "U" (for severe cases) techniques to reduce excess periungual tissue.[2,6] While these procedures are more invasive and require better analgesic control, complication and recurrence rates appear to be low.[16] Patients who decline surgery may be treated with a chemical avulsion instead, using a 50% urea occlusive dressing overnight to promote softening of the nail.[2,3] Figure 3. A patient with retronychia pre- (left) and post- (right) complete surgical nail avulsion. Regardless of the treatment used, retronychia can persist even with minimal trauma to the foot. Static disorders of the foot, if present, should be corrected to minimize predisposition to trauma. For long-term management of symptoms, it is critical for patients to wear open-toed shoes or close-toed shoes with an adequate toe box to permit ample space for movement and decreased pressure on the toenails. Medical or surgical intervention will be more effective if properly fitted footwear is also incorporated. The patient in this case should consider having her feet sized and begin wearing wide-width shoes, if warranted. She should also seek shoe brands that advertise wider toe boxes. Over the long term, nonconstrictive footwear will help to reduce loading pressure on the toes, enhance stability of the feet, and prevent future trauma to the involved nail plate and matrix.[9] The prognosis for this patient, if treated appropriately, is slow nail regrowth with minimal long-term deformity. Complete resolution without treatment is improbable because of the chronic inflammatory nature of retronychia, which can lead to persistent discomfort and complications if unaddressed. Permanent nail loss is also unlikely, as the new nail plate is typically expected to grow back normally. Finally, rapid onset of pain requiring immediate surgical intervention is not characteristic of retronychia; this patient's pain developed gradually, and conservative treatments are often the initial approach for mild-to-moderate cases, with surgery reserved for more advanced or unresponsive cases. The prognosis of retronychia can vary widely based on the severity and duration of symptoms, as well as the treatment approach used. Mild cases can be managed conservatively. In moderate-to-severe cases, regular nail regrowth will most likely be restored through surgical nail avulsion. Regardless of the chosen treatment, patients need to be educated on properly fitted footwear with generous toe space, as this accounts for a significant risk factor of progression and recurrence. If detected early and managed effectively through appropriate treatment methods in conjunction with addressing the original triggering factor(s), positive outcomes can be expected. Retronychia is largely underreported and underrepresented in current literature. Provisional diagnoses may be confusing, and symptoms may be overlooked by the patient and/or healthcare provider, especially if they are mild or nonspecific. It is important for clinicians to be familiar with distinct indicators of this disease to avoid unnecessary treatments and promote optimal health outcomes.
Medscape
20-05-2025
- Health
- Medscape
Teenaged Boy With Epigastric Pain
Editor's Note: The Case Challenge series includes difficult-to-diagnose conditions, some of which are not frequently encountered by most clinicians, but are nonetheless important to accurately recognize. Test your diagnostic and treatment skills using the following patient scenario and corresponding questions. If you have a case that you would like to suggest for a future Case Challenge, please email us at ccsuggestions@ with the subject line "Case Challenge Suggestion." We look forward to hearing from you. Background and Initial Presentation A 13-year-old boy presents to the emergency department (ED) with a history of epigastric pain, vomiting, malaise, polyuria, and a 12-lb weight loss during the past 3 months. His parents have brought him to the emergency department today because his pain and vomiting are worsening. They report no history of hematuria, hematemesis, fever, or chills. They also do not note any other associated symptoms, prior surgeries, or medical conditions. The patient was previously seen by his pediatrician and is undergoing a workup. Upper gastroendoscopy performed at a nearby hospital 2 weeks ago had revealed chronic gastritis with erosive changes in the antral region. Triple treatment for Helicobacter pylori , however, did not lead to any improvement. Abdominal ultrasonography also performed at that time showed mild nephrocalcinosis. Family history is negative for diabetes mellitus and porphyria. Physical Examination and Workup Upon physical examination, the child is thin and mildly ill-appearing. His temperature is 98.6°F (37°C); his pulse has a regular rhythm, with a rate of 80 beats/min; and his blood pressure is 120/70 mm Hg. The patient's respirations are regular and unlabored at 14 breaths/min. The child is in mild distress secondary to his epigastric discomfort. The examination of the head and neck is normal, except that the oropharynx appears slightly dry. He has no dysmorphic facial features. His lungs are clear to auscultation, and normal respiratory effort is noted. The S1 and S2 heart sounds are normal, and no murmurs are detected. The abdomen is soft but tender to deep palpation in the epigastric region. The patient's extremities show no edema, and brisk capillary refill is noted. His skin is clear except in the gluteal region, where a nodular eczematous lesion is present. Routine laboratory tests reveal a normal complete blood count and normal values for sodium, potassium, chloride, bicarbonate, and magnesium. The patient's blood urea nitrogen and serum creatinine values are elevated (22.4 mg/dL and 1.8 mg/dL, respectively). The calcium level is elevated at 14.4 mg/dL, which is confirmed with an ionized calcium level of 7.2 mg/dL. The phosphorus level is low, at 5 mg/dL. Hepatic aminotransferase values are slightly elevated (aspartate aminotransferase, 61 U/L; alanine aminotransferase, 201 U/L) and the bilirubin level is 0.7 mg/dL. Alkaline phosphatase level is somewhat elevated at 137 IU/L. A chest radiograph is obtained (Figure). Figure. Chest radiograph demonstrating combined hilar lymphadenopathy and reticulonodular interstitial infiltrates in the upper lung zone. (Note: This image is from a different patient with a similar condition.) The patient is hospitalized. During the hospital course, additional laboratory tests are performed. The thyroid hormone levels are in the normal range, but the parathyroid hormone level is low, at 10.91 pg/mL (normal range, 15-65 pg/mL). Vitamin D metabolites are not measured. The serum angiotensin-converting enzyme (ACE) level is normal, at 32.7 U/L (normal range, 12-42 U/L). The results of a purified protein derivative test are negative. Urinalysis performed on several occasions shows a specific gravity of 1.003 and a pH of 5, with normal urinary sediment. Urinary culture findings are negative. On several occasions, marked hypercalciuria is observed, with a calcium level of 14 mg/kg and a urinary calcium/creatinine ratio (mmol/mmol) that ranges from 2.5 to 3.5. No glycosuria or aminoaciduria is noted. Ultrasonography is performed, on which the parathyroid glands appear normal. Renal ultrasonography confirms mild nephrocalcinosis around the renal calices. A renal biopsy is performed. The specimen exhibits tubulointerstitial nephritis associated with tubular calcium deposits. Other findings include interstitial infiltration by mononuclear cells, interstitial fibrosis, tubular necrosis, and atrophy. Dystrophic calcifications are present in some of the tubules. Negative results are obtained for immunoglobulin (Ig) A, IgG, IgM, and C3 on immunofluorescence analysis. Immunohistochemical analysis reveals inflammatory cellular substrate CD68, macrophages, and lymphoid population. No glomerular abnormalities are evident. The clinical picture of this patient was dominated by nonspecific constitutional symptoms, such as malaise, vomiting, abdominal cramps, and weight loss. He had no history of maculopapular rashes, erythema nodosum, arthritis, chronic lymphocytopenia, hepatomegaly, splenomegaly, lymphadenopathy, or uveitis. He also did not have any coughing or exertional dyspnea. The child did have vomiting and polyuria, which were caused by hypercalcemia. The renal biopsy specimen indicated acute tubulointerstitial nephritis associated with tubular calcium deposits, without glomerular abnormalities. In addition, the chest radiograph demonstrated combined hilar lymphadenopathy and reticulonodular interstitial infiltrates in the upper lung zone. The chest radiography findings, when considered along with the hypercalcemia, rash, and renal biopsy results, are consistent with stage 2 radiographic sarcoidosis.[1] Symptoms of Fanconi syndrome in children are failure to thrive, growth retardation, and rickets, which does not describe this patient. Diagnosis is by demonstrating glucosuria, phosphaturia, and aminoaciduria.[2] Although a variety of glomerular lesions, including IgA nephropathy, are described as glomerular damage in sarcoidosis, they are not distinguishable from their primary form.[3] Moreover, this patient has a tubulointerstitial nephritis which is seen more often in sarcoidosis than IgA nephropathy (the latter is typically more a glomerulonephritis). Bartter syndrome, a rare inherited salt-losing renal tubular disorder, is associated with secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic alkalosis and low to normal blood pressure,[4] which does not describe this patient. Discussion Hypercalcemia and/or hypercalciuria may occur in less than a third of cases of pediatric sarcoidosis.[1] Measuring baseline serum calcium levels is recommended to screen for abnormal calcium metabolism in patients with sarcoidosis, even in asymptomatic patients.[5] A rare cause of clinically manifested hypercalcemia is vitamin D intoxication, but it is associated with significant morbidity. It may be caused by endogenous synthesis of 1,25-dihydroxyvitamin D from subcutaneous fat necrosis, granulomatous disease, or by excessive exogenous vitamin D intake.[1] Hypercalcemia may also result from primary hyperparathyroidism or from increased levels of parathyroid hormone-related protein caused by certain malignancies.[6] Lastly, hypercalcemia may occur in patients with hypophosphatemia, vitamin A intoxication, or blue-diaper syndrome, or it may occur in association with use of certain medications, most notably hydrochlorothiazide and other thiazide diuretics.[6] An intact parathyroid hormone (PTH) level at the time of hypercalcemia is pivotal in narrowing the differential diagnosis. If the PTH level is high, the child must be thoroughly investigated for the cause of hyperparathyroidism and may require urgent surgical intervention. If the PTH level is low (as it was in this patient), additional calciotropic hormones may be assayed if appropriate testing is available. Identifying the abnormal calciotropic hormone might allow diagnosis of the specific cause, elucidation of the mechanism for the hypercalcemia, and optimal treatment.[7] Sarcoidosis is a multisystem disorder characterized by an increased cellular immune response to an unknown antigen and the formation of noncaseating granulomas in affected tissues. Although the lungs and lymph nodes are the predominant sites affected by sarcoidosis, other organs, such as the eyes, bone marrow, kidneys, liver, and spleen, may also be involved.[1,8] Cases of extrapulmonary sarcoidosis affecting the kidneys are rare; most such cases present with nephrocalcinosis or nephrolithiasis. Renal failure is an extremely uncommon manifestation.[1] As noted previously, an intact PTH level at the time of hypercalcemia is important in narrowing the differential diagnosis. If the PTH level is high, the child must be completely investigated for the cause of hyperparathyroidism and may need urgent surgery. If the PTH level is low (as it was in this patient), additional calciotropic hormones may be examined if appropriate testing is available. Identification of the abnormal calciotropic hormone might facilitate diagnosis of the cause, clarification of the mechanism for the hypercalcemia, and appropriate treatment.[7] Hypercalcemia in sarcoidosis is relatively uncommon.[1] It is usually caused by the autonomous production of 1,25-dihydroxyvitamin D (calcitriol) by macrophages within the granuloma. These macrophages can convert 25-hydroxyvitamin D, produced by the liver, into calcitriol by possessing the 1-alpha-hydroxylase enzyme. Calcitriol then travels to the intestinal cells and promotes luminal absorption of calcium and phosphate into the circulation. Hypercalcemia is accompanied by hypercalciuria and, eventually, nephrocalcinosis (as seen in this case). Hypercalcemia may also eventually cause renal failure both by causing dehydration and by inducing renal vasoconstriction, thereby reducing the glomerular filtration rate.[1,6] Excess PTH production can produce significant bone loss, which is not seen in this patient.[7] High levels of magnesium are not directly linked to sarcoidosis. The lungs and lymph nodes are the predominant sites that are affected by sarcoidosis,[9] and also the liver in children,[8] although other organs, including the eyes, bone marrow, kidneys, and spleen, may additionally be involved.[1,8,9] Pediatric sarcoidosis is a rare disease, with an estimated incidence of 0.6 to 1.02 per 100,000 children.[8] Two distinct forms of childhood sarcoidosis appear to exist. Older children usually present with a multisystem disease similar to the adult manifestation, with frequent lymphadenopathy and pulmonary involvement. They also show generalized signs and symptoms, such as fever and malaise. In contrast, early-onset childhood sarcoidosis is a unique form of the disease characterized by the triad of rash, uveitis, and arthritis, usually in patients who are younger than 4 years.[9] Pulmonary disease and abnormal findings on chest radiography are more common in children with sarcoidosis aged 8-15 years, compared with those younger than 4 years.[9] Bilateral hilar adenopathy is the most common finding on chest radiography in children; it occurs in almost all cases. It is typically symmetrical, although rarely it may occur unilaterally. Pulmonary parenchymal involvement is common and most often appears radiographically as an interstitial pattern; however, nodular, alveolar, and fibrotic patterns have also been noted. Of note, although chest radiography may be sufficient for the diagnosis, high-resolution chest CT may be helpful in evaluating lung changes[1,9] and is superior to conventional CT for detecting and demonstrating diagnostic findings in the lungs.[10] Other uncommon manifestations include pleural effusion, pneumothorax, pleural thickening, calcification, and cor pulmonale, and atelectasis.[1] The serum ACE level is increased in many patients with sarcoidosis. Sensitivity and specificity as a diagnostic test is limited. The serum ACE level may be normal in patients with active disease.[9] Many children with sarcoidosis have palpable peripheral lymph glands. The lymph nodes generally are firm, nontender, discrete, and easily movable. They neither ulcerate nor form draining sinuses. The glands involved most often are the cervical, axillary, epitrochlear, and inguinal glands. In the neck, the posterior triangle nodes are affected more frequently than the nodes in the anterior triangle. The enlarged peripheral lymph nodes are the most accessible tissue for biopsy. Hepatosplenomegaly often occurs in children with sarcoidosis at some point in their clinical course, but clinically significant hepatic dysfunction is rare. Mild elevation in biochemical liver function test values is common (as it was in this patient), but severe liver involvement is uncommon in children.[9] Ocular involvement is very common in children with sarcoidosis, and a complete ophthalmologic evaluation, including a slit-lamp examination, is essential (particularly in young children). Sarcoidosis may affect any part of the eye or orbit. Anterior uveitis (also called "iritis" or "iridocyclitis") is the most frequently noted lesion.[9] The patient should be examined for a decrease in visual acuity, eye pain, a red eye, or any other visual aberration that can indicate a posterior or anterior uveitis.[8] Sarcoid-associated uveitis can be acute or chronic and may vary from an isolated iridocyclitis to a bilateral panuveitis syndrome. If left untreated, the disease may cause synechiae, corneal opacities, glaucoma, and, eventually, blindness.[1,9] Renal involvement is not well characterized in published series of childhood sarcoidosis. Histopathologic studies have revealed epithelioid granuloma formation, interstitial infiltration by mononuclear cells, interstitial fibrosis, tubulitis, tubular atrophy, mesangial hyperplasia, glomerular fibrosis, and vascular involvement.[9] Corticosteroids remain the cornerstone of therapy for sarcoidosis, but immunosuppressive, cytotoxic, and immunomodulatory agents are viable therapeutic options for patients who do not respond to or experience adverse effects from corticosteroids. The published data most extensively documents treatment with methotrexate,[1,8] but favorable responses have been noted with leflunomide, azathioprine, and antimalarial and antimicrobial agents, as well as with tumor necrosis factor–alpha inhibitors. The dosage and the duration of corticosteroid therapy must often be individualized. Treatment is continued until the clinical manifestations of the disease resolve or show significant improvement.[9,11] For cutaneous sarcoidosis that cannot be controlled by local treatment, consideration of oral glucocorticoids is suggested.[11 More recently, repository corticotropin injection been suggested as an alternative in patients who are on high-dose prednisone.[9] The patient in this case received prednisone, 1.5 mg/kg per day for 1 month, with gradual tapering of the dose over the following 4-5 months. Hypercalcemia and renal failure reversed completely, as did the pulmonary changes seen on radiography. No recurrence was observed at 1-year follow-up. Renal nephrocalcinosis persisted, however, despite symptomatic and biochemical improvement. During corticosteroid therapy, measurement of the urinary beta-2-microglobulin concentration by sodium dodecyl sulfate polyacrylamide gel electrophoresis proved a valuable monitoring tool for assessing recovery of the tubular impairment. Chest radiography obtained after 3 weeks of corticosteroid therapy showed resolution of the findings seen in the original chest radiograph. This patient represents a rare case of sarcoidosis presenting with acute renal failure and hypercalcemia as the initial manifestations. Sarcoidosis should be considered in the differential diagnosis of hypercalcemia and renal failure,[1,9] occurring singly or in combination. Corticosteroids are useful for treatment.[1,8,9] As noted previously, hypercalcemia in sarcoidosis is uncommon[1] and usually results from autonomous production of 1,25-dihydroxyvitamin D (calcitriol) by macrophages within the granuloma. These macrophages can convert 25-hydroxyvitamin D, produced by the liver, into calcitriol by possessing the 1-alpha-hydroxylase enzyme. At that point, calcitriol travels to the intestinal cells and facilitates luminal absorption of calcium and phosphate into the circulation. Hypercalcemia is accompanied by hypercalciuria and, eventually, nephrocalcinosis.[1,6,9] A rare cause of clinically manifested hypercalcemia is vitamin D intoxication, which may be caused by excessive exogenous vitamin D intake.[1,6,9] Hypercalcemia may also result from primary hyperparathyroidism or from increased levels of parathyroid hormone-related protein caused by certain malignancies.[1,6,9] As noted previously, corticosteroids are the cornerstone of therapy for sarcoidosis,[1,9] but viable therapeutic options include immunosuppressive, cytotoxic, and immunomodulatory agents for patients who do not respond to or experience adverse effects from corticosteroids. Published data mainly documents treatment with the immunosuppressant methotrexate,[1,8] but favorable responses have been seen with leflunomide, mycophenolate mofetil, azathioprine, and antimalarial and antimicrobial agents, as well as with tumor necrosis factor-alpha inhibitors. Treatment options do not include fungicides, antiviral drugs, and antibiotics; granulomatous pulmonary infections caused by mycobacteria and fungi should have been ruled out.[1] For cutaneous sarcoidosis that is not controlled by local treatment, oral glucocorticoids could be considered.[11] For patients on high-dose prednisone, a suggested alternative is repository corticotropin injection.[9] The dosage and the duration of corticosteroid therapy must often be individualized. The treatment is continued until the clinical manifestations of the disease resolve or show significant improvement.[9,11]
